Sie sind auf Seite 1von 79

1-Maternal disease producing antibodies, which cross the placenta and cause disease in the neonate include:

Idiopathic thrombocytopaenic purpura

Thyrotoxicosis

Diabetes mellitus

Myasthenia gravis

Huntington’s Chorea

Maternal antibodies may cross the placenta as early as the first trimester. Anti- cardiolipin antibodies as seen in SLE may cause heart block. Anti-D antibodies may cause erythroblastosis fetalis. Neonatal thyrotoxicosis may be due to maternal anti-thyroid antibodies where the mother has Graves disease or Hashimoto’s thyroiditis. Dystrophia myotonica may manifest in infants of affected mothers but the mechanism is likely to be genetic. Maternal antibodies to HIV do cross the placenta but only the virus, and not antibodies to it, cause the disease. Although maternal diabetes can cause problems in the neonate, this is due to the high concentration of glucose in the maternal blood crossing the placenta, not the anti- bodies. Anti-acetylcholine receptor antibodies transferred across the placenta may cause transient myasthaenia gravis which lasts 4-6 weeks in about 15% of neonates born to affected mothers. Maternal autoantibodies seen in ITP may cross the placenta and lead to destruction of fetal platelets resulting in moderate to severe thrombocytopaenia. T T F T F

2-Regarding HiB vaccination, which of the following are true?

It is a live vaccine

It is contra-indicated in a child with a history of convulsions

It is given with the MMR immunisation

Boosters are given at monthly intervals for 3 months in children under 1 year old

It must not be given as a single injection with DPT

DTaP/IPV/Hib is a combined vaccine which contains the following active ingredients: purified high dose diphtheria toxoid; purified tetanus toxoid; five purified components of the Bordetella pertussis bacteria; three strains of inactivated polio virus and a purified component of Haemophilus influenzae type b bacteria attached to a tetanus toxoid carrier protein. It is usually given to babies at

the age of two, three and four months but check the NHS immunisation schedule

for the most recent details: http://www.immunisation.nhs.uk/

F F F T F

3-Which of the following are true regarding BCG vaccination?

Efficacy is demonstrated by a hypersensitivity response to vaccine administration

It is contraindicated in neonates

It offers protection against infection with Mycobacterium bovis as well as Mycobacterium tuberculosis

It should be injected subcutaneously

It contains a live attenuated virus

Bacillus of Calmette and Gurin (BCG) is a vaccine against tuberculosis that is prepared from a strain of the attenuated (weakened) live bovine tuberculosis bacillus, Mycobacterium bovis (a bacteriumm, not a virus), that has lost its virulence in humans through serial propagation in artificial media. The bacilli retain sufficient immunogenicity to behave as a reasonably effective vaccine for the prevention of human tuberculosis, particularly in the prevention of TB meningitis and disseminated disease in early childhood. Protection against pulmonary disease in later life is less certain. BCG vaccine should always be given intradermally as subcutaneous administration is likely to be associated with adverse effects including local abscess formation and suppurative lymphadenitis. The Mantoux test results in a cutaneous hypersensitivity response to administered PPD (purified protein dericative), but neither a cutaneous response to the vaccine or to PPD are sufficient or required to demonstrate vaccine efficacy. F F T F F

4-In order to ensure meticulous care in hygiene, which measure is NOT acceptable when preparing bottle feeds?

Using boiled waterwhich measure is NOT acceptable when preparing bottle feeds? Allowing the liquid to cool Placing in

Allowing the liquid to coolacceptable when preparing bottle feeds? Using boiled water Placing in the refrigerator Using sterilised bottles Warming

Placing in the refrigeratorbottle feeds? Using boiled water Allowing the liquid to cool Using sterilised bottles Warming the milk

Using sterilised bottlesAllowing the liquid to cool Placing in the refrigerator Warming the milk twice Babies are at

Warming the milk twiceto cool Placing in the refrigerator Using sterilised bottles Babies are at risk of infection due

Babies are at risk of infection due to their relatively poor immunity and by warming the milk twice, you are allowing bacteria a chance to culture in the milk.5

5-MMR contraindications include which of the following?

Child treated with 2mg/kg/day prednisolone

Children with history of neonatal seizures

Previous vomiting after egg ingestion

History of febrile convulsions

Severe eczema

Contraindications include: acute fever, recent immunoglobulin administration, administration of another live vaccine in the past 3 weeks, immunosuppression, allergy to neomycin or kanamycin, pregnancy. Steroids, such as prednisolone, given to children either orally or rectally at a daily dose of 2mg/kg/day for at least one week or 1mg/kg/day for one month should be deemed as a contraindication and administration on live vaccines should be postponed for at least 3 months after immunosuppressive treatment has stopped.

In children with a significant history of an anaphylactic reaction to eggs, or who have had egg allergy and chronic severe asthma the vaccination should be administered in hospital. The vaccine is not however contraindicated in such patients. T F F F F

6-Which of the following are true regarding Oral Polio Vaccine (OPV)?

It contains 3 strains of live attenuated virus

It is contraindicated in the presence of diarrhoea

It is contraindicated in children on oral steroids 2mg/kg/day

Use of the inactive vaccine reduces the carriage of the wild virus

Incidence of vaccine associated poliomyelitis is negligible

Oral polio ('Sabin') vaccine is given by mouth in contrast to the inactivated ('Salk') vaccine (IPV) which is given IM. Polio vaccines are usually given at two months, three months and four months of age, with a booster before school, usually between 3 and 5 years of age and again, before leaving school, between 15 and 19 years old. Boosters thereafter are not normally necessary, unless travelling to an area where polio is common, or likely to be exposed to people with polio.

The oral vaccine contains live virus particles which have been attenuated to reduce the risk of neurological disease. The risk of vaccine associated poliomyelitis is small but not negligible and this together with the elimination of wild polio from the European Region was the principle reason for the change to the routine use of IPV in the UK in 2006.

Three types of poliomyelitis virus (Types 1, 2 and 3) are included in the vaccine.

Contraindications:

Postpone if acute illness with pyrexia, diarrhoea/vomiting

Immunodeficiency/treatment with high doses of steroids/immunosuppresants

First four months of pregnancy

T T T T F

7-Which of the following children should be given BCG immunisation?

Normal healthy infants with Asian mothers going to Bangladesh

Migrant from Africa

A 13-year-old child who is moving to a high risk area but who has had immunisation as an infant

Child who has a contact with active pulmonary TB

Infant with a grandparent born in a high risk area

BCG is recommended for the following groups if BCG immunisation, as evidenced by a characteristic scar, has not previously been carried out and they are negative for tuberculoprotein hypersensitivity:

all infants living in areas where the incidence of tuberculosis is greater than 40 per 100 000;

infants with a parent or grandparent born in a country with an incidence of tuberculosis greater than 40 per 100 000;

previously unvaccinated new immigrants from countries with a high incidence of tuberculosis;

contacts of those with active respiratory tuberculosis;

health service staff

veterinary staff

staff working in prisons, in residential homes and in hostels for refugees and the homeless;

those intending to stay for more than 1 month in countries with a high incidence of tuberculosis

neonates, infants, children or adults where immunisation is requested. T T F T T

8-Which of the following are true regarding the Meningococcal vaccine which is used in the UK immunisation schedule?

It protects against types B and C

It can cause meningoencephalitis

It is contraindicated in HIV infection

3 injections are given from 6 months of age

It is a live attenuated vaccine

Almost all childhood meningococcal disease in the UK is caused by Neisseria meningitidis serogroups B and C. Meningococcal Group C conjugate vaccine protects only against infection by serogroup C; it can be given from 2 months of age. After early adulthood the risk of meningococcal disease declines, and immunisation is not generally recommended after the age of 25 years.

Meningococcal Group C conjugate vaccine provides long-term protection against infection. The recommended schedule consists of 3 doses given at 3, 4 and 12 months.

Side-effects of meningococcal Group C conjugate vaccine include redness, swelling, and pain at the site of the injection, mild fever, irritability, drowsiness, dizziness, nausea, vomiting, diarrhoea, headache, myalgia, rash, urticaria, pruritus, malaise, lymphadenopathy, hypotonia, paraesthesia, hypoaesthesia, and syncope. Hypersensitivity reactions and seizures have been reported rarely. Symptoms of meningism have also been reported rarely, but there is no evidence that the vaccine causes meningococcal C meningitis. There have been very rare reports of Stevens- Johnson syndrome. The CSM has advised that vaccination provides benefit in terms of lives saved and disabilities prevented.

Currently meningococcal vaccine is a purified heat stable extract from the

polysaccaride outer capsule of Neisseria meningitidis.

4 F

9-Which of the following are true regarding vaccines?

Diptheria vaccine is a toxoid

Pertussis vaccine is a killed bacillus

Injected polio vaccine is a live attenuated virus

BCG is a live attenuated bacillus

Measles is a live attenuated virus

Previously virulent micro-organisms that have been inactivated (with chemicals or heat) include vaccines against influenza, cholera, plague, and hepatitis A. Most such vaccines may have incomplete or short-lived immune responses and are likely to require booster shots.

Live, attenuated vaccines typically provoke more durable immunological responses. Examples include yellow fever, measles, rubella, and mumps. BCG is a live tuberculosis strain. The oral polio vaccine is a live attenuated virus but injected polio vaccine is inactivated.

Inactivated toxic compounds (Toxoids) from micro-organisms include tetanus and diphtheria. The pertussis vaccine is acellular and made from part of the pertussis cell. T F F T T

10-Which of the following are true regarding deranged cellular immunity?

It often presents with severe viral infections

It is associated with Di George syndrome

It is associated with gram-positive severe infections

It is associated with prematurity

It occurs in agammaglobulinaemia

Cell mediated immunity is mediated by T cells and is involved in control of viral infections. Abnormalities of cell mediated immunity occur in Di George syndrome because of the absence of T cell maturation secondary to thymus abnormalities. Protection from bacterial infection is classically associated with B cell abnormalities and the consequent inability to produce antibodies. Prematurity is associated with immaturity of the immune system but this mainly manifests as

abnormal antibody production. X-linked agammaglobulinaemia is a pure B cell defect and affected children have normal cell mediated immunity.

T T F F F

11-Which of the following regarding the F c component of antibody are true?

Determines antigen binding specificity

Determines the ability to cross the placenta

Determines the ability to bind with mast cells

When produced in excess, excreted in urine as Bence-Jones protein

Determines metabolic half life of the whole molecule

The basic unit of an antibody is a monomer. An antibody can be monomeric, dimeric, trimeric, tetrameric, pentameric, etc. The monomer is a Y-shaped molecule that consists of two identical heavy chains and two identical light chains connected by disulphide bonds.

Each half of the forked end of the Y-shaped monomer is called the Fab fragment. It

is composed of one constant and one variable domain of each the heavy and the

light chain, which together shape the antigen binding site. The F c fragment is the

stem of the Y and is composed from two heavy chains. It binds to various cell receptors and complement proteins. In this way it mediates different physiological effects of antibodies (opsonisation, cell lysis, mast cell, basophil and eosinophil degranulation and other processes).

Bence-Jones proteins are free immunoglobulin light chains. F T T F T

12-The advantages of breast feeding are:

Reduces the risk of bacterial contamination

Protection of infection via passage of maternal antibody (IgE)

Promoted colonisation with lactobacilli

Improves maternal bonding

Cheaper

There are many economical, social and medical advantages of breast feeding. Maternal antibodies in the breast milk are IgA not IgE. T F T T T

13-Which of the following is NOT a contra-indication to MMR vaccination:

Children receiving high-dose cortico-steroidsthe following is NOT a contra-indication to MMR vaccination: Children with an anaphylactic allergy to egg

Children with an anaphylactic allergy to eggvaccination: Children receiving high-dose cortico-steroids Children with an allergy to neomycin Children with an acute

Children with an allergy to neomycinChildren with an anaphylactic allergy to egg Children with an acute febrile illness Children who have

Children with an acute febrile illnessallergy to egg Children with an allergy to neomycin Children who have received an immunoglobulin injection

Children who have received an immunoglobulin injection within the last 3 monthsallergy to neomycin Children with an acute febrile illness All of the above are contra-indications as

All of the above are contra-indications as written in the BNF except egg allergy - this is a common misconception. In children with a significant history of an anaphylactic reaction to eggs, or who have had egg allergy and chronic severe asthma, the vaccination should be administered in hospital. The vaccine is not however contraindicated in such patients.

Contraindications include: acute fever, recent immunoglobulin administration, administration of another live vaccine in the past 3 weeks, immunosuppression, allergy to neomycin or kanamycin, pregnancy. Steroids, such as prednisolone, given to children either orally or rectally at a daily dose of 2mg/kg/day for at least one week or 1mg/kg/day for one month should be deemed as a contraindication and administration on live vaccines should be postponed for at least 3 months after immunosuppressive treatment has stopped. 2

14-Which vaccination is given by the intradermal route usually?

Inactivated PolioWhich vaccination is given by the intradermal route usually? Meningococcal C MMR DTP BCG BCG is

Meningococcal Cis given by the intradermal route usually? Inactivated Polio MMR DTP BCG BCG is the only

MMRintradermal route usually? Inactivated Polio Meningococcal C DTP BCG BCG is the only vaccine given intradermally.

DTProute usually? Inactivated Polio Meningococcal C MMR BCG BCG is the only vaccine given intradermally. The

BCGroute usually? Inactivated Polio Meningococcal C MMR DTP BCG is the only vaccine given intradermally. The

BCG is the only vaccine given intradermally. The rest are given by the intramuscular or deep subcutaneous route. 5

15-Which statements concerning the MMR vaccination are correct?

Previous measles is a contraindication

The first dose is given at 6 months

A booster dose is given at 3-5 years

Parotid swelling is a recognised side effect

Idiopathic thrombocytopenic purpura is a rare complication

Any child who has had measles, mumps or rubella should be given the MMR vaccination regardless of previous infection (BNF). The first dose is given at 12- 15 months with a pre-school booster. ITP is a rare complication and the risk of developing ITP is much less with MMR than with the actual diseases of measles, mumps and rubella. Parotid swelling is also a recognised side effect. F F T T T

16-Which vaccination is NOT included in the 2, 3, 4 month ages of a child according to the UK immunisation schedule?

Polioages of a child according to the UK immunisation schedule? Hib DTP Meningococcal C BCG BCG

Hibof a child according to the UK immunisation schedule? Polio DTP Meningococcal C BCG BCG is

DTPa child according to the UK immunisation schedule? Polio Hib Meningococcal C BCG BCG is usually

Meningococcal Caccording to the UK immunisation schedule? Polio Hib DTP BCG BCG is usually given at birth

BCGthe UK immunisation schedule? Polio Hib DTP Meningococcal C BCG is usually given at birth in

BCG is usually given at birth in high risk neonates or at ages 10-14.

5

17-Regarding a squint in a child, which statement is correct?

The child does not require further investigation if it has been present for over 6 monthsRegarding a squint in a child, which statement is correct? May be regarded as within acceptable

May be regarded as within acceptable limits if transient and only lasting a few seconds up to the age of 18 monthsinvestigation if it has been present for over 6 months Is more frequent in children who

Is more frequent in children who have not been vaccinatedand only lasting a few seconds up to the age of 18 months Is more frequent

Is more frequent in children with myopia than hypermetropiaIs more frequent in children who have not been vaccinated In a younger child is more

In a younger child is more likely to be divergent rather than convergentIs more frequent in children who have not been vaccinated Is more frequent in children with

It is important to refer children with squints over the age of 6 months for further investigation and prevent permanent blindness in that eye. Transient squints of only a few seconds duration may be acceptable up to 18 months of age. Hypermetropia is a common cause of squints in children. Convergent squints are more common. 2

18-Consider the options presented below. Which screening does NOT occur in the United Kingdom?

Heel Prick Test to screen for congenital hypothyroidismbelow. Which screening does NOT occur in the United Kingdom? Red Reflex to screen for congenital

Red Reflex to screen for congenital cataractHeel Prick Test to screen for congenital hypothyroidism Echocardiogram in children at 6 weeks to screen

Echocardiogram in children at 6 weeks to screen for / diagnose cardiac structural diseasehypothyroidism Red Reflex to screen for congenital cataract Otoacoustic emission to screen for hearing impairment Heel

Otoacoustic emission to screen for hearing impairment6 weeks to screen for / diagnose cardiac structural disease Heel prick test to screen for

Heel prick test to screen for phenylketonuriaOtoacoustic emission to screen for hearing impairment Auscultation is used to pick up murmurs in children,

Auscultation is used to pick up murmurs in children, not routine echocardiograms at 6 weeks. The Guthrie test (heel prick test/blood spot screening test) in the UK screens for phenylketonuria, congenital hypothyroidism, sickle cell disorders, cystic fibrosis and Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD). 3

19-A Primary Prevention

B

Secondary Prevention

C Tertiary Prevention

D

Health Promotion

E Health Education

F

Child Health Surveillance

G Public health

The definitions below are best described by which of the options above? Each option may be used once, more than once, or not at all.

It

is important to consider the child in society and the importance of looking

at

child health in the community as a whole. Secondary prevention is

reduction of prevalence of disease by shortening duration or diminishing the

impact through early detection and prompt intervention (eg screening). Health promotion is any measure that improves health or prevents disease.

Public health is a science preventing disease, prolonging life and promoting health through the organised efforts of society.

Scenario 1 Reduction in number of new cases of a disease, disorder or condition (accidents)

Primary Prevention

Correct answer

Scenario 2 Any activity which promotes health through learning

Health Education

Correct answer

Scenario 3 Reduction of impairment and disability, and minimising suffering (e.g. multidisciplinary approach of a child with Down syndrome)

Tertiary Prevention

Correct answer

It is important to consider the child in society and the importance of looking at child health in the community as a whole. Primary prevention is reducing number of cases of disease, disorder, conditions or accident from the very onset. Secondary prevention is reduction of prevalence of disease by shortening duration or diminishing the impact through early detection and prompt intervention (e.g. screening). Tertiary prevention is the reduction of impairment and disability in a child with a pre-existing illness or condition. Health promotion is any measure that improves health or prevents disease. Public health is a science preventing disease, prolonging life and promoting health through the organised efforts of society.

20-A Polio

B Diptheria

C

Tetanus

D Pertussis

E

Measles

F Mumps

G

Rubella

H Haemophilus influenzae type B

It

is important to recognise the symptoms of these serious diseases especially if

a child has not been vaccinated against them.

Scenario 1 A child develops fever and parotid gland enlargement

Mumps

Correct answer

Scenario 2 A child has prolonged URTI with paroxysms of coughing, followed by a whoop with vomiting. Diagnosis is confirmed by a nasopharyngeal culture.

Pertussis

Correct answer

Scenario 3 A child has a throat infection with pharyngeal exudates. There is membrane formation and upper airway obstruction.

Diptheria

Correct answer

Scenario 4 A child develops mild fever and is then left with residual paralysis.

Polio

Correct answer

Scenario 5 A child has a maculopapular rash, fever, coryza, cough and conjunctivitis

Measles

Correct answer

These conditions are not common due to the widespread uptake of immunisations in the UK, however it is important to recognise the symptoms of these serious diseases especially if a child has not been vaccinated against them.

21-Which of the following are true regarding CD4 Lymphocytes?

Anaphylaxis is due to fixing antibodies

They are involved in delayed type hypersensitivity

They secrete IL-2 in response to antigen stimulus

They are the predominant intra-epithelial lymphocytes in the gut

They are processed in the thymus

CD4+ve lymphocytes are known as helper T cells and interact with MHC Class II molecules whereas CD8+ve T cells interact with MHC Class I molecules. CD4+ve cells are involved in antigen specific responses as well as delayed type hypersensitivity and secrete a number of cytokines including IL-2 in response to antigen stimulation. Intra-epithelial lymphocytes in the gut are dominated by T cells bearing the gamma/delta receptor and are not CD4+ve. All T cells are processed in the thymus where self-reactive cells are deleted. F T T F T

22-Which of the following are true, regarding antibodies?

Hereditary angio-oedema is associated with C1 esterase inhibitor deficiency

The activity of hereditary angio-oedema is exacerbated by the menstrual cycle

Urticaria may have a non-allergic cause

Anaphylaxis is due to fixing antibodies

Serum sickness is due to antibodies against antigens found on RBC during a blood transfusion

Hereditary angio-oedema is due to the absence or low level of C1 esterase inhibitor (C1-INH), although it may also be caused by the abnormal function of C1-INH in the presence of normal levels of the protein. Stress such as trauma or surgery may precipitate attacks, which may also be exacerbated by changes in the menstrual cycle. Urticaria occurs as a result of IgE interaction with basophils leading to the release of mediators, which result in mucosal oedema. While it is thus usually due to allergy, the trigger for an urticarial response may not always be found. Anaphylaxis is due to IgE antibodies. Serum sickness is due to antibodies forming to foreign proteins such as anti-sera to snake bites and occurs 7-10 days after injection of the foreign protein. Antibodies to red cells cause Type II hypersensitivity reactions (also known as cytotoxic reactions). T T T F F

23-Only IgE-mediated allergic reactions can be formally tested by skinprick testing. Adverse reactions to which of the following substances can be tested in this manner?

Morphineof the following substances can be tested in this manner? Radiocontrast media Scombrotoxins Colloid plasma expanders

Radiocontrast mediato which of the following substances can be tested in this manner? Morphine Scombrotoxins Colloid plasma

Scombrotoxinswhich of the following substances can be tested in this manner? Morphine Radiocontrast media Colloid plasma

Colloid plasma expandersreactions to which of the following substances can be tested in this manner? Morphine Radiocontrast media

LatexLatex can induce allergy through IgE bound to mast cells. All the others induce histamine

Latex can induce allergy through IgE bound to mast cells.

All the others induce histamine release via their direct effects on mast cells, except for scombroid fish poisoning, which is related to the heat-stable toxin in tuna, mackerel, mahi mahi, etc and causes immediate diffuse redness, diarrhoea and vomiting. 5

24-Which of the following adverse food reactions is mediated by IgE- dependent mechanisms and hence can be ascertained by skinprick testing?

Monosodium glutamate in Chinese foodand hence can be ascertained by skinprick testing? Scombroid fish poisoning Sulphites on prepacked salads

Scombroid fish poisoningby skinprick testing? Monosodium glutamate in Chinese food Sulphites on prepacked salads Salicylate-induced urticaria

Sulphites on prepacked saladsglutamate in Chinese food Scombroid fish poisoning Salicylate-induced urticaria Kiwi fruit Kiwi fruit is a

Salicylate-induced urticariafood Scombroid fish poisoning Sulphites on prepacked salads Kiwi fruit Kiwi fruit is a member of

Kiwi fruitSulphites on prepacked salads Salicylate-induced urticaria Kiwi fruit is a member of the latex-associated foods and

Kiwi fruit is a member of the latex-associated foods and adverse reactions to this fruit are mediated by IgE. All the others are examples of food intolerance, so that detailed history-taking is essential to making the correct diagnosis. Scombroid fish poisoning causes immediate diffuse redness, diarrhoea and vomiting following the consumption of fish such as tuna, mackerel and mahi mahi. Monosodium glutamate causes abdominal bloating and vomiting – the so-called ‘Chinese restaurant syndrome’. Sulphites on prepacked salads causing asthma is called the ‘Salad-bar syndrome’. 5

25-In a patient with anaphylaxis, which of the following should be given to inhibit the important late-phase reaction?

Antihistaminesshould be given to inhibit the important late-phase reaction? Epinephrine Leukotriene inhibitor Hydrocortisone NSAID 14

Epinephrineshould be given to inhibit the important late-phase reaction? Antihistamines Leukotriene inhibitor Hydrocortisone NSAID 14

Leukotriene inhibitorfollowing should be given to inhibit the important late-phase reaction? Antihistamines Epinephrine Hydrocortisone NSAID 14

Hydrocortisoneshould be given to inhibit the important late-phase reaction? Antihistamines Epinephrine Leukotriene inhibitor NSAID 14

NSAIDbe given to inhibit the important late-phase reaction? Antihistamines Epinephrine Leukotriene inhibitor Hydrocortisone 14

Hydrocortisone blocks the generation of leukotrienes and prostaglandins, and hence prevents the late-phase reaction often characterised by asthma. It should be given intravenously/intramuscularly at a dose of 100–200 mg.

None of the other agents listed above affect this aspect of anaphylaxis. Indeed leukotriene inhibitors and NSAIDs are not part of the emergency management of acute anaphylaxis.

Approximately 30% of deaths related to anaphylaxis occur as a consequence of this late-phase reaction. 4

26-In an 18-year-old, recurrent and/or severe infections with which of the following organisms would make you suspect immunodeficiency associated with hypogammaglobulinaemia?

Haemophilus influenzaeimmunodeficiency associated with hypogammaglobulinaemia? Streptococcus pyogenes Herpes simplex virus Candida spp

Streptococcus pyogeneswith hypogammaglobulinaemia? Haemophilus influenzae Herpes simplex virus Candida spp Pneumocystis jiroveci

Herpes simplex virusHaemophilus influenzae Streptococcus pyogenes Candida spp Pneumocystis jiroveci Infections with

Candida spp spp

Pneumocystis jiroveciStreptococcus pyogenes Herpes simplex virus Candida spp Infections with Haemophilus influenzae and Streptococcus

Infections with Haemophilus influenzae and Streptococcus pneumoniae occur with this condition, not Streptococcus pyogenes. Pneumocystis jiroveci (formerly P. carinii), viral and candidal infections are associated with T-cell deficiencies, including HIV infection. 1

27-Immunological investigations in a patient with renal disease are important in the diagnostic work-up, which of the following statements is correct?

Henoch–Schönlein purpura is associated with IgG in the mesangiumwork-up, which of the following statements is correct? SLE is typically associated with sparse deposits of

SLE is typically associated with sparse deposits of IgG and complement in the glomerulipurpura is associated with IgG in the mesangium C3 nephritic factor is associated with mesangiocapillary

C3 nephritic factor is associated with mesangiocapillary glomerulonephritis type Iwith sparse deposits of IgG and complement in the glomeruli Minimal-change glomerulonephritis is associated with

Minimal-change glomerulonephritis is associated with hypocomplementaemiaassociated with mesangiocapillary glomerulonephritis type I Antiglomerular basement-membrane antibodies are associated

Antiglomerular basement-membrane antibodies are associated with Goodpasture’s diseasemesangiocapillary glomerulonephritis type I Minimal-change glomerulonephritis is associated with hypocomplementaemia 15

Minimal-change glomerulonephritis is not associated with complement activation. C3 nephritic factor is associated with mesangiocapillary glomerulonephritis type 2, not type 1. SLE nephritis is an immune complex problem; hence deposits of IgG and complement are prolific.

Henoch–Schonlein purpura is typically associated with IgA in the mesangium, hence immunological examination of both a blood and renal biopsy will help to define the underlying process. 5

28-Anti-Ro antibodies in isolation (negative ANA) occur in which of the following conditions?

Sjögren’s syndrome(negative ANA) occur in which of the following conditions? Sicca syndrome Systemic lupus erythematosus (SLE)

Sicca syndromeof the following conditions? Sjögren’s syndrome Systemic lupus erythematosus (SLE) Scleroderma Polymyositis

Systemic lupus erythematosus (SLE)conditions? Sjögren’s syndrome Sicca syndrome Scleroderma Polymyositis ANA-negative lupus is uncommon.

Sclerodermasyndrome Sicca syndrome Systemic lupus erythematosus (SLE) Polymyositis ANA-negative lupus is uncommon. ANA-negative

Polymyositis ANA-negative lupus is uncommon. ANA-negative SLE patients are usually Ro- positive and have skin rashes with or without photosensitivity. In Sjögren’s syndrome, Ro and La antibodies commonly coexist. Sicca syndrome is not typically associated with autoantibodies. 3syndrome Systemic lupus erythematosus (SLE) Scleroderma 29-Haemolytic disease of the newborn is typically restricted

29-Haemolytic disease of the newborn is typically restricted to the presence of Rhesus antigens on red cells rather than ABO antigens. Predominantly, such anti-Rh antibodies cross the placenta during the third trimester.

Which of the following statements best explains the background physiology?

Antibodies to ABO blood groups are IgM, whereas antibodies to Rhesus antigens are IgGstatements best explains the background physiology? Antibodies to ABO blood groups are IgG, whereas antibodies

Antibodies to ABO blood groups are IgG, whereas antibodies to Rhesus antigens are IgMare IgM, whereas antibodies to Rhesus antigens are IgG Antibodies to ABO blood groups are IgA,

Antibodies to ABO blood groups are IgA, whereas antibodies to Rhesus antigens are IgGare IgG, whereas antibodies to Rhesus antigens are IgM Antibodies to Rhesus antigens are IgD, whereas

Antibodies to Rhesus antigens are IgD, whereas anti-ABO blood groups are IgMare IgA, whereas antibodies to Rhesus antigens are IgG Antibodies to Rhesus antigens are IgE, whereas

Antibodies to Rhesus antigens are IgE, whereas anti-ABO blood groups are IgGantibodies to Rhesus antigens are IgG Antibodies to Rhesus antigens are IgD, whereas anti-ABO blood groups

IgG antibodies to Rhesus antigens can cross the placenta during the last trimester, whereas ABO antibodies are IgM and hence cannot cross the placenta. The function of serum IgD is unknown. The transplacental passage of immunoglobulin only applies to IgG. 1

30-Which of the following are true regarding T-cells?

60-80% of total white cell count

They are more frequent than B cells

They mature in the thymus

They are associated with memory responses

Defects can occur in Di George Syndrome

Normal adult levels of white blood cells are 4,500-11,000 cells per microlitre of blood. Lymphocytes account for approximately 25-45% of the total white blood cell count; the normal range is 1,000-4,800 lymphocytes per microlitre of blood in adults and older children (> 5 years of age), with higher circulating numbers in infants and young children. Of the total lymphocytes, 60-80% are T cells and approximately 15% are B cells. Mature functional T cells undergo differentiation and maturation in the thymus. F T T T T

31-In skin prick testing for sensitivity to respi ratory allergens, the cutaneous reaction is influenced by which of the following?

Recent use of inhaled salbutamol

Regular inhaled steroids

Cigarette smoking

Severe eczema

Oral antihistamine use

The diagnosis of allergic disorders is dependent on a careful history exploring the relationship between symptom onset and exposure to potential allergens. Determination of specific IgE (either through serum antibody, by RAST or skin- prick tests) is useful in either confirming a clinical impression of allergy, or sometimes in identifying a particular culprit from a small number of carefully- selected potential allergens.

Skin-prick tests when carried out correctly provide a quick, visual, semi- quantitative determination of the presence of specific IgE (e.g. to house dust mite or to peanut) present on the surface of mast cells in the skin. A positive result is indicated by a wheal (± erythema) at the test site 10-15 minutes after placing prick tests for the allergen and a positive (histamine) control. The test is relatively non-invasive and parents and children often appreciate the benefit of seeing (if not scratching) the result, without the need to return to clinic at a later date for results. It is important that negative and positive controls are tested together with potential allergens. Testing may be difficult in children with extensive skin disease (eczema) and false positives are common in highly atopic individuals, leading to real difficulties in test interpretation. For this and other reasons, blind testing of a wide range of allergens in the search for a hidden culprit is rarely helpful and not recommended.

False negatives are likely in children who have taken recent antihistamine preparations (they should be avoided 48 hours prior to the test) and to a lesser extent in those recently exposed to systemic or topical (but not inhaled) steroids.

Skin-prick testing is often useful in confirming a clinical diagnosis of food allergy where diagnosis can be followed by dietary exclusion. The issues are more complex with aero-allergens (e.g. for house-hold pets or outdoor pollen) as avoidance is usually more difficult. F F F T T

32-Which of the following are true regarding complement?

IgA activates complement via the classical pathway

Severe burns activate complement

The alternative pathway is activated when complement levels in the classical pathway run out

C 2 is involved in both the classical and alternative pathways

C 5 is increased in meningococcal meningitis

The complement cascade consists of 3 separate pathways that converge in a final common pathway. The pathways include the classic pathway (C1qrs, C2, C4), the alternative pathway (C3, factor B, properdin), and the mannan-binding pathway (mannan-binding lectin [MBL]). These 3 pathways converge at the component C3.

The classical pathway is activated by immune complexes, whereas the alternative pathway is activated by lipopolysaccharide component of the cell wall of gram

negative bacteria. Both result in conversion of C3 to C3b, which activates the lytic complement sequence. The terminal complement pathway consists of all proteins activated after C3; the most notable of these is the C5-C9 group of proteins known collectively as the membrane attack complex (MAC), of which C5 has been implicated in meningococcal meningitis. F T F F T

33-Which of the following are true with regard to IgE?

It can cross the placenta

Serum concentration is equal to that of IgG

It is acutely increased in an acute asthma attack

It is associated with type II hypersensitivity

It is associated with mast cell function

The antigen-specific IgE interacts with mast cells and eosinophils to protect the host against the invading parasite. The same antibody-cell combination is also responsible for typical allergy or immediate (Type I) hypersensitivity reactions such as hayfever, asthma, hives and anaphylaxis. F F T F T

34-Vasculitis occurs in which of the following conditions?

Systemic lupus erythematosus

Immune thrombocytopenic purpura

Necrotising enterocolitis

Stevens – Johnson syndrome

Kawasaki disease

Vasculitides are characterised by inflammatory destruction of blood vessels, occurring in veins (phlebitis) or arteries (arteritis). Some conditions have vasulitis as their main feature and include:

HSP

Kawasaki Disease

Polyarteritis nodosa

Wegener’s granulomatosis

Takayasu’s arteritis

Giant cell arteritis (temporal arteritis)

In some conditions vasculitis may be a symtpom and include:

SLE

Lymphomas

Infections

In response to some drugs as part of Stevens-Johnson syndrome

Purpura in ITP results from thrombocytopenia. There is no exact cause for necrotising colitis known, but it is not thought to be due to a vasculitis. T F F T T

35-Which of the following are absolute contra-indications to Pertussis immunisation?

Epilepsy

Family history of convulsions after immunisation

Eczema

Autism

Previous severe local reaction to immunisation

Since 2006 acellular pertussis vaccines have been used for routine immunisation in the UK and this change, together with an assessment of vaccine reactions has led to a significant change in the contraindications and warnings relating to pertussis immunisation.

The only remaining absolute contraindications for pertussis-containing vaccines are:

Confirmed anaphylactic reaction to a previous dose of pertussis-containing vaccine, or

Confirmed anaphylactic reaction to neomycin, streptomycin or polymyxin B (which may be present in trace amounts in the vaccine).

Of particular note (and in contrast to previous advice), immunisation with pertussis-containing vaccines should not be withheld despite a previous history of convulsions, high fever, hypotonic-hyporesponsive episodes (HHE), persistent crying, screaming or severe local reaction following immunisation.

By the time of school entry children in the UK should have received 4 doses of pertussis-containing vaccines (DTaP/Hib/IPV at ages 2, 3 & 4 months, and DTaP

or dTaP at age 3.5 to 4 years (a preschool booster). The booster dose at school entry was added in 2006 at the same time that the change was made from whole-

cell to acellular pertussis component vaccines.

4 F

36-The following immunoglobulin are responsible for:

IgA leads to bacterial agglutination

IgD is involved in inhibition of viral replications

IgE : Type 1 sensitivity reaction

IgG : neutralisation of bacterial toxins

IgM : complement activation

Immunoglobulins are antibodies. They are made of gamma globulins and in humans there are five types.

1. IgA is found in mucosal areas, such as the gut and respiratory tract. It is also found in saliva, tears and breast milk. It prevents bacterial infection y leading to agglutination.

2. IgD upregulates cellular response to viral infections by activating basophils and mast cells.

3. IgE binds to allergens and triggers histamine. It is associated with a Type I hypersensitivity reaction.

4. IgG is split into 4 further subclasses. It provides the majority of antibody based immunity. It is the only antibody that crosses the placenta.

5. IgM leads to complement activation. T F T T T

37-Which of the following mediators attract cells in inflammation?

Interleukin 4

Interleukin 8

Leukotrine B4

C3b

C5a

IL-4: involved in proliferation of B cells, and the development of T cells and mast cells. Important role in allergic responses.

IL-8: Neutrophil chemotaxis

C3b acts as an opsonizer.

C5a is an anaphylatoxin, causing the release of histamine from mast cells. It is also an effective leucocyte chemoattractants, causing the accumulation of white blood cells, especially neutrophil granulocytes, at sites of complement activation.

Leukotrienes are important agents in the inflammatory response. Some such as LTB4 have a chemotactic effect on migrating neutrophils, and as such help to bring the necessary cells to the tissue. Leukotrienes also have a powerful effect in vasoconstriction particularly of venules and of bronchoconstriction, they also increase vascular permeability. F T T F T

38-Which of the following are true statements regarding common variable immune deficiency?

Patients are particularly prone to viral infections

Circulating B cell numbers are usually normal

IgG levels are normal

It typically manifests autosomal recessive inheritance

Patients are at an increased risk of malignancy

Common variable immunodeficiency (CVID) is a disorder that involves the following: (1) low levels of most or all of the immunoglobulin (Ig) classes, (2) a lack of B lymphocytes or plasma cells that are capable of producing antibodies, and (3) frequent bacterial infections.

CVID is a common immune disorder and is, in fact, the most prevalent primary immunodeficiency. It can be inherited in autosomal dominant or recessive manner. However, it is diverse, both in its clinical presentation and in the types of deficiency. Although decreased serum levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) are characteristic, approximately 50% of patients with the deficiency also have diminished serum immunoglobulin M (IgM) levels and T- lymphocyte dysfunction. The primary cause of CVID remains unknown. In patients with CVID, the risk of certain malignancies is high. Lymphomas of a B-

cell phenotype are of particular concern and malignancy is most likely associated with the Epstein-Barr virus. F T F F T

39-Which of the following antibodies are correctly linked with a disease with which they are associated?

Antiesterase Ab in myasthaenia

Antiendomysial Ab and coeliac disease

Anti-acetylcholine antibodies and spinal muscular atrophy

21 hydroxylase Ab and congenital adrenal hyperplasia

Antiepidermal Ab and vitiligo

Autoantibodies may be present in patients with myasthenia (antibodies against the acetylcholine receptor) and vitiligo but do not match those given in the question.

F T F F F

40-Which of the following is/are true regarding overwhelming septicaemia in post-splenectomy patients?

It

can be fully prevented with vaccination

It

usually involves gram-negative organisms

It

is only a significant problem for two/three years post splenectomy

It

is due to hypogammaglobulinaemia

Immunisation after removal of the spleen has a better outcome

There is an increased risk of pyogenic infections, including pneumonia, septicemia and meningitis caused by pneumococcus and other polysaccharide encapsulated organisms (e.g. Haemophilus influenzae type b) after splenectomy.

The mechanism for this immune deficiency is not entirely clear - it would seem to be multifactorial. Immunoglobulin levels generally remain normal. As

pneumococcal infection is numerically the greatest risk, prophylaxis with penicillin

is used. However, particularly in young children, awareness of the risks from other

infections should be maintained.

Vaccination with pneumococcal and Haemophilus influenzae type B vaccines may

diminish the risk but do not remove the need to give penicillin. Immunisation

should be performed prior to elective splenectomy.

4 F

41-In a 16-year-old female with systemic lupus erythematosus, which of the following investigations/statements is true?

CRP is typically normal in non-infected patients with active diseasewhich of the following investigations/statements is true? Rheumatoid factor is positive in < 5% of patients

Rheumatoid factor is positive in < 5% of patientsnormal in non-infected patients with active disease Neutropenia is more common than lymphopenia The low-dose

Neutropenia is more common than lymphopeniaRheumatoid factor is positive in < 5% of patients The low-dose oral contraceptive pillis contraindicated

The low-dose oral contraceptive pillis contraindicated5% of patients Neutropenia is more common than lymphopenia Pulmonary fibrosis is a common disease complication

Pulmonary fibrosis is a common disease complicationThe low-dose oral contraceptive pillis contraindicated The CRP is often normal in SLE even if the

The CRP is often normal in SLE even if the patient has active disease. An elevated CRP therefore may indicate the presence of infection.

Rheumatoid factor tests can be positive in up to 40% of affected individuals. Lymphopenia is more common than neutropenia. The oral contraceptive pill is not contraindicated and pulmonary fibrosis is an unusual late complication. 1

42-Which of the following arthritides is frequently associated with the eye inflammation described?

Juvenile idiopathic arthritis and uveitisfrequently associated with the eye inflammation described? Seronegative arthropathies and retinal vasculitis Systemic

Seronegative arthropathies and retinal vasculitisdescribed? Juvenile idiopathic arthritis and uveitis Systemic lupus erythematosus and pars planitis

Systemic lupus erythematosus and pars planitisuveitis Seronegative arthropathies and retinal vasculitis Behçet’s disease and uveitis Sarcoid and anterior

Behçet’s disease and uveitisvasculitis Systemic lupus erythematosus and pars planitis Sarcoid and anterior uveitis Behçet’s disease is

Sarcoid and anterior uveitisand pars planitis Behçet’s disease and uveitis Behçet’s disease is most commonly associated with

Behçet’s disease is most commonly associated with posterior uveitis, although hypopyon can also be seen. The other typical pairings should be juvenile idiopathic arthritis with scleritis, seronegative arthropathies with anterior uveitis, SLE with retinal vasculitis and sarcoid with uveitis. 4

43-High titres of antithyroid microsomal and antithyroglobulin antibodies would suggest which of the following diagnoses in a patient presenting with a complaint of tiredness?

Hashimoto’s thyroiditisReidel’s thyroiditis Graves disease Hypoparathyroidism Idiopathic hypothyroidism This finding in Hashimoto’s

Reidel’s thyroiditisHashimoto’s thyroiditis Graves disease Hypoparathyroidism Idiopathic hypothyroidism This finding in

Graves diseaseHashimoto’s thyroiditis Reidel’s thyroiditis Hypoparathyroidism Idiopathic hypothyroidism This finding in

Hypoparathyroidismthyroiditis Reidel’s thyroiditis Graves disease Idiopathic hypothyroidism This finding in Hashimoto’s

Idiopathic hypothyroidismthyroiditis Graves disease Hypoparathyroidism This finding in Hashimoto’s thyroiditis is

This finding in Hashimoto’s thyroiditis is characteristic, but lower titres can occur in Reidel’s thyroiditis and Graves disease. High titres of these antibodies in euthyroid individuals indicate the possibility of future thyroid failure, but this may be many years away; hence the need for thyroid function tests every 1–2 years in such individuals. 1

44-Which of the following statements in relation to skin disease is true?

Eye involvement is unusual in benign mucous membrane pemphigoidfollowing statements in relation to skin disease is true? The rash of herpes gestationis most commonly

The rash of herpes gestationis most commonly affects the chestinvolvement is unusual in benign mucous membrane pemphigoid Pemphigus is associated with subepidermal bullae

Pemphigus is associated with subepidermal bullaerash of herpes gestationis most commonly affects the chest Epidermolysis bullosa acquisita is strongly associated with

Epidermolysis bullosa acquisita is strongly associated with HLA-DR4the chest Pemphigus is associated with subepidermal bullae Nasal swabs should be routinely checked in patients

Nasal swabs should be routinely checked in patients with recurrent staphylococcal abscessesbullosa acquisita is strongly associated with HLA-DR4 Eye involvement is common in pemphigoid. Pemphigoid is

Eye involvement is common in pemphigoid. Pemphigoid is associated with subepidermal bullae, and in pemphigus they are intraepidermal. Epidermolysis bullosa acquisita is associated with DR-2 and not DR-4. The rash of herpes gestationis is typically found on the lower abdomen. 5

45-A 16-year-old suffers recurrent, proven bacterial chest infections requiring regular antibiotic treatment.

Which of the following is the best way to exclude antibody deficiency?

Serum immunoglobulinsfollowing is the best way to exclude antibody deficiency? Immunoglobulin subclasses Specific antibodies to haemophilus

Immunoglobulin subclassesway to exclude antibody deficiency? Serum immunoglobulins Specific antibodies to haemophilus and pneumococci

Specific antibodies to haemophilus and pneumococciexclude antibody deficiency? Serum immunoglobulins Immunoglobulin subclasses Complement levels Mannan-binding proteins 25

Complement levelsimmunoglobulins Immunoglobulin subclasses Specific antibodies to haemophilus and pneumococci Mannan-binding proteins 25

Mannan-binding proteinsSerum immunoglobulins Immunoglobulin subclasses Specific antibodies to haemophilus and pneumococci Complement levels 25

Normal specific antibodies to pneumococci, haemophilus and also tetanus will exclude a significant antibody deficiency. Immunoglobulins and subclasses can be normal even though there is a profound absence of specific antibodies. 3

46-A patient collapses during induction with a general anaesthetic.

Which of the following investigations will be most useful in subsequently establishing an IgE-mediated process (anaphylactic mechanism)?

Elevated serum tryptase at approximately 1 hour after collapsean IgE-mediated process (anaphylactic mechanism)? Total serum IgE level Skin-prick tests to anaesthetic agents

Total serum IgE levelserum tryptase at approximately 1 hour after collapse Skin-prick tests to anaesthetic agents Serum/plasma C3 and

Skin-prick tests to anaesthetic agentsat approximately 1 hour after collapse Total serum IgE level Serum/plasma C3 and C4 levels Specific

Serum/plasma C3 and C4 levelsTotal serum IgE level Skin-prick tests to anaesthetic agents Specific IgE to latex Although tryptase measurements

Specific IgE to latextests to anaesthetic agents Serum/plasma C3 and C4 levels Although tryptase measurements indicate mast-cell

Although tryptase measurements indicate mast-cell degranulation, they do not point to the triggering mechanism.

Total serum IgE is a test with little clinical value except in the interpretation of specific IgE measurements.

Skin-prick tests performed at neat and 1:10 dilutions are the recognised investigations for identifying which anaesthetic agents were problematic.

Plasma complement levels are rarely helpful.

Specific IgE to latex for investigating latex allergy may be helpful but is unlikely to be the cause of a reaction at induction, i.e. before the surgeon has a gloved hand inside the patient. 3

47-In a patient with suspected hereditary angio-oedema (HAE), which of the following is most likely to be helpful in identifying this clinical condition?

Persistently low C3 levels, including between attackslikely to be helpful in identifying this clinical condition? Persistently low C4 levels, including between attacks

Persistently low C4 levels, including between attacksPersistently low C3 levels, including between attacks Search for a paraprotein Drug history of taking ACE

Search for a paraproteinincluding between attacks Persistently low C4 levels, including between attacks Drug history of taking ACE inhibitors

Drug history of taking ACE inhibitorslow C3 levels, including between attacks Persistently low C4 levels, including between attacks Search for a

Presence of urticaria with angio-oedematous swellingsA lack of C1 inhibitor occurs in approx 85% of cases of HAE and a

A lack of C1 inhibitor occurs in approx 85% of cases of HAE and a functional deficiency in the remaining 15%. C4 levels usually remain low even between attacks, whereas C3 levels remain normal. The measurement of C4 is therefore helpful in identifying those 15% of patients who have a normal amount of C1 inhibitor which functions poorly but gives normal levels when measured. Paraproteins can occasionally bind C1 inhibitor to create a functional deficiency. ACE inhibitors may exacerbate the angioedema in HAE and hence should be avoided. Urticaria is never a feature of HAE. A drug history would be useful but would not identify the HAE condition. 2

48-A teenager complains of an immediate intense itching in her throat when eating apples, but says that she can eat cooked ones. She mentions that she has allergic rhinitis but the current symptoms occur in April and May and not the typical June/July period associated with grass pollen.

What is the most likely diagnosis?

Birch-associated oral allergy syndromewith grass pollen. What is the most likely diagnosis? Food intolerance Allergy to the wax coating

Food intolerancelikely diagnosis? Birch-associated oral allergy syndrome Allergy to the wax coating on apples Latex allergy

Allergy to the wax coating on applesBirch-associated oral allergy syndrome Food intolerance Latex allergy Salicylate sensitivity The birch

Latex allergyFood intolerance Allergy to the wax coating on apples Salicylate sensitivity The birch pollen-induced oral allergy

Salicylate sensitivityAllergy to the wax coating on apples Latex allergy The birch pollen-induced oral allergy syndrome occurs

The birch pollen-induced oral allergy syndrome occurs with stoned fruits, apples, carrots and potatoes. However, this only happens with the raw form as cooking denatures the allergen. The birch-tree pollen season is usually in April/May, giving the typical rhinitis symptoms. Actual throat swelling is unusual. Immediate symptoms (minutes) are untypical of food intolerance and the wax coating on apples is not a cause of allergies. Latex allergy can be associated with certain foods such as bananas, avocado, kiwi and melon, but this allergen is heat-stable. Most apples contain a considerable amount of salicylate, which can induce urticaria in aspirin-sensitive individuals; however, this is not usually associated with pharyngeal itching. 1

49-A teenager who has been doing work experience presents with red weals and itchy hands within 20 minutes of wearing latex gloves.

Which of the following mechanisms is most likely to be relevant?

Contact dermatitisof the following mechanisms is most likely to be relevant? Complement-mediated Immune complex-mediated Delayed-type

Complement-mediatedmechanisms is most likely to be relevant? Contact dermatitis Immune complex-mediated Delayed-type hypersensitivity

Immune complex-mediatedto be relevant? Contact dermatitis Complement-mediated Delayed-type hypersensitivity IgE-mediated sensitivity This

Delayed-type hypersensitivitydermatitis Complement-mediated Immune complex-mediated IgE-mediated sensitivity This is an immediate

IgE-mediated sensitivityImmune complex-mediated Delayed-type hypersensitivity This is an immediate hypersensitivity (type-1) reaction and

This is an immediate hypersensitivity (type-1) reaction and hence will be IgE- mediated. Delayed-type (4) hypersensitivity, (e.g. contact dermatitis, Mantoux test), has an onset that usually exceeds 24 hours. Complement-mediated (type-2 hypersensitivity) and immune complex (type-3 hypersensitivity) reactions typically produce vascular damage and therefore bullae and petechiae would predominate in the skin. 5

50-During the last trimester, IgG is actively transported across the placenta to supply passive immunity to the foetus.

Which disease occurring during pregnancy is most likely to lead to the neonate having low immunoglobulin levels and hence being prone to bacterial infections?

Intestinal lymphangiectasialevels and hence being prone to bacterial infections? Systemic lupus erythematosus Myasthenia gravis Ulcerative

Systemic lupus erythematosusprone to bacterial infections? Intestinal lymphangiectasia Myasthenia gravis Ulcerative colitis Prematurity Typically,

Myasthenia gravisIntestinal lymphangiectasia Systemic lupus erythematosus Ulcerative colitis Prematurity Typically, intestinal

Ulcerative colitisSystemic lupus erythematosus Myasthenia gravis Prematurity Typically, intestinal lymphangiectasia has its

Prematuritylupus erythematosus Myasthenia gravis Ulcerative colitis Typically, intestinal lymphangiectasia has its onset during

Typically, intestinal lymphangiectasia has its onset during pregnancy, and is sometimes diagnosed when the neonate is investigated for bacterial infection. Although systemic lupus erythematosus with severe nephrotic syndrome could also produce hypogammaglobulinaemia, this would be a rare occurrence in a neonate. Myasthenia gravis due to the transfer of maternal IgG antibodies across the placenta can result in neonatal myasthenia. Significant protein loss from the gut in

ulcerative colitis is highly unusual, especially in a neonate. Prematurity does reduce the time for placental transfer of IgG whilst the foetus is in utero and hence produces a so-called ‘physiological hypogammaglobulinaemia’, but this is not a disease. 1

51-You see a schoolboy who has a part-time job ‘washing up’ at a restaurant. He presents with an eczematous rash on his hands suggestive of contact dermatitis, possibly related to wearing latex gloves at work. You discuss confirmatory tests.

Which of the following tests is most likely to be helpful establishing the diagnosis?

Atopy patch testingis most likely to be helpful establishing the diagnosis? Skin-prick testing Patch testing Intradermal testing Direct

Skin-prick testingbe helpful establishing the diagnosis? Atopy patch testing Patch testing Intradermal testing Direct exposure tests to

Patch testingthe diagnosis? Atopy patch testing Skin-prick testing Intradermal testing Direct exposure tests to gloves Patch

Intradermal testingAtopy patch testing Skin-prick testing Patch testing Direct exposure tests to gloves Patch testing is the

Direct exposure tests to glovestesting Skin-prick testing Patch testing Intradermal testing Patch testing is the classical method for investigating

Patch testing is the classical method for investigating contact dermatitis (which is T-lymphocyte mediated). Skin-prick testing investigates IgE-mediated reactions, typically to aeroallergens and food. The atopy patch test is a research tool used to investigate the possible role of food in exacerbations of eczema. Direct exposure to gloves will simply support the history. Intradermal testing is usually reserved in the UK for drug testing. 3

52-A 15-year-old girl with partial lipodystrophy presents with a 3- month history of increasing swelling of her legs, which is now up to her knees. Urinalysis shows heavy proteinuria but no haematuria. A diagnosis of nephrotic syndrome is therefore made.

Which investigation is most likely to help in the definition of the underlying renal pathology?

IgA enterocyte antibodiesto help in the definition of the underlying renal pathology? Complement studies Antineutrophil cytoplasmic antibodies

Complement studiesof the underlying renal pathology? IgA enterocyte antibodies Antineutrophil cytoplasmic antibodies (ANCA) Antiglomerular

Antineutrophil cytoplasmic antibodies (ANCA)renal pathology? IgA enterocyte antibodies Complement studies Antiglomerular basement membrane antibodies (anti-GBM) 29

Antiglomerular basement membrane antibodies (anti-GBM)underlying renal pathology? IgA enterocyte antibodies Complement studies Antineutrophil cytoplasmic antibodies (ANCA) 29

Antistreptolysin titre (ASOT)Nephrotic syndrome in an individual with partial lipodystrophy is likely to be mesangiocapillary nephritis with

Nephrotic syndrome in an individual with partial lipodystrophy is likely to be mesangiocapillary nephritis with C3 nephritic factor. The latter is an autoantibody, and interacts with the complement pathway to give a low C3 with a normal C4 level. Serum immunoglobulins are likely to show reduced IgG and raised IgM levels, which is typical of the nephrotic syndrome. Anti-GBM antibodies are likely to be negative as the patient is young and there is no haematuria or pulmonary involvement, which would be suggestive of Goodpasture’s syndrome. 2

53-A 16-year-old youth presents with lethargy and abdominal bloating. He has lost 5 kg in weight over the last 6 months. Examination confirms a thin teenager with obvious pallor.

Which is the most appropriate serological test to investigate possible malabsorption?

Striated muscleserological test to investigate possible malabsorption? IgG antiendomysial antibodies IgA antigliadin antibodies IgA

IgG antiendomysial antibodiestest to investigate possible malabsorption? Striated muscle IgA antigliadin antibodies IgA enterocyte antibodies IgA

IgA antigliadin antibodiesmalabsorption? Striated muscle IgG antiendomysial antibodies IgA enterocyte antibodies IgA antiendomysial antibodies

IgA enterocyte antibodiesIgG antiendomysial antibodies IgA antigliadin antibodies IgA antiendomysial antibodies Small-bowel, duodenal biopsy

IgA antiendomysial antibodiesIgA antigliadin antibodies IgA enterocyte antibodies Small-bowel, duodenal biopsy obtained via an upper endoscopy

Small-bowel, duodenal biopsy obtained via an upper endoscopy is the ‘gold standard’ investigation for coeliac disease. However, serological testing using IgA antiendomysial antibodies is the most discriminating of the above choices. The newer test, becoming increasingly available, is IgA antitransglutaminase. IgG antiendomyseal antibodies will be of value in the diagnosis of coeliac disease in IgA-deficient individuals, because in these individuals the IgA antiendomysial antibody test will be negative, therefore it is vital to check IgA levels in patients with suspected coeliac disease. 5

54-Antibodies to which one of the following are found most frequently in patients with myasthenia gravis?

Acetylcholine esterasewhich one of the following are found most frequently in patients with myasthenia gravis? Acetylcholine receptors

Acetylcholine receptorswhich one of the following are found most frequently in patients with myasthenia gravis? Acetylcholine esterase

Myelinfollowing are found most frequently in patients with myasthenia gravis? Acetylcholine esterase Acetylcholine receptors 30

Striated muscleTensilon Myasthenia is characterised by fatigability of striated muscle. It is an autoimmune disease with

TensilonStriated muscle Myasthenia is characterised by fatigability of striated muscle. It is an autoimmune disease with

Myasthenia is characterised by fatigability of striated muscle. It is an autoimmune disease with antibodies against acetylcholine receptors. There are at least four subgroups of myasthenia which differ in age and sex spread, systemic muscle/ocular muscle/both, thymic involvement, antibody titres, HLA associations and treatment. Antibodies to acetylcholine esterase (the enzyme which breaks down acetylcholine) would, in theory, increase the amount of available acetylcholine. Myelin is not a primary target for autoantibodies in this disease. Tensilon (edrophonium) has short-acting anticholinesterase activity and is used to aid diagnosis of the disease. Electromyography (EMG) may be helpful in diagnosis, and around 90% of patients have raised titres of anti-acetylcholine receptor antibodies. 2

55-Which of the following is associated with hereditary angio-oedema?

Low levels of C1 inhibitorof the following is associated with hereditary angio-oedema? High levels of C1 inhibitor C3 deficiency High

High levels of C1 inhibitorwith hereditary angio-oedema? Low levels of C1 inhibitor C3 deficiency High levels of C4 complement during

C3 deficiencyLow levels of C1 inhibitor High levels of C1 inhibitor High levels of C4 complement during

High levels of C4 complement during an attackof C1 inhibitor High levels of C1 inhibitor C3 deficiency Deficiency of the membrane-attack complex (C5b–9)

Deficiency of the membrane-attack complex (C5b–9)C3 deficiency High levels of C4 complement during an attack This disorder is due to low

This disorder is due to low levels of the C1 inhibitor of the complement system and is one of the commonest complement deficiencies. Low levels of the C1 inhibitor allow C1 to act on C4 and C2. This in turn produces kinin-like products that cause the angio-oedema. Low levels of C4 are found during an attack. C3 levels are normal. Membrane-attack complex deficiencies leave patients particularly susceptible to neisserial infection. In a few cases C1 inhibitor levels are normal but defective. The skin lesions are not itchy, unlike allergic urticaria. Painful intestinal involvement can occur. Triggers include stress, infection and menstruation. Danazol may be used in treatment. Acquired C1 inhibitor deficiency may be associated with lymphoproliferative disease and infection. 1

56-Which of the following is associated with the correct disease?

HLA DR4 – ankylosing spondylitisof the following is associated with the correct disease? HLA B27 – Behçet’s disease HLA B5

HLA B27 – Behçet’s diseasethe correct disease? HLA DR4 – ankylosing spondylitis HLA B5 – haemochromatosis HLA A3 – multiple

HLA B5 – haemochromatosisspondylitis HLA B27 – Behçet’s disease HLA A3 – multiple sclerosis HLA Cw6 –

HLA A3 – multiple sclerosisBehçet’s disease HLA B5 – haemochromatosis HLA Cw6 – psoriasis Regions of HLA are found on

HLA Cw6 – psoriasis– haemochromatosis HLA A3 – multiple sclerosis Regions of HLA are found on chromosome 6: HLA-A

Regions of HLA are found on chromosome 6:

HLA-A

Haemochromatosis (A3)

HLA-B

Behçet’s syndrome (B5)

 

Ankylosing spondylitis (B27)

 

Reiter’s syndrome (B27)

HLA-C

Psoriasis (Cw6)

HLA-DR

Goodpasture’s syndrome (DR2)

 

Multiple sclerosis (DR2)

 

Addison’s disease(DR3)

 

Rheumatoid disease (DR4)

5

57-Which of the following statements concerning hyperacute rejection after renal transplantation is correct?

Occurs at least three days after surgeryhyperacute rejection after renal transplantation is correct? Is successfully treated with ciclosporin A Is caused by

Is successfully treated with ciclosporin Ais correct? Occurs at least three days after surgery Is caused by ciclosporin A Is mediated

Is caused by ciclosporin Aafter surgery Is successfully treated with ciclosporin A Is mediated by preformed circulating antibodies Is largely

Is mediated by preformed circulating antibodiestreated with ciclosporin A Is caused by ciclosporin A Is largely a B-cell-mediated response Hyperacute rejection

Is largely a B-cell-mediated responseA Is mediated by preformed circulating antibodies Hyperacute rejection of a donor kidney may only take

Hyperacute rejection of a donor kidney may only take a few minutes once the organ has been vascularised. Preformed circulating antibodies react with MHC class 1 antigens on the transplanted kidney. A reaction ensues involving complement molecules, an influx of polymorphs and the aggregation of platelets.

Blood vessels supplying the organ become obstructed causing ischaemia. Ciclosporin A has no role in the treatment of hyperacute reactions: the only treatment is removal of the organ. However, circulating antibodies mean the next organ must be MHC 1-matched. Matching for MHC 2 is well known to prolong graft survival. The use of ciclosporin has revolutionised donor organ survival. It modifies T-cell responses, but is itself nephrotoxic. 4

58-Which of the following diseases is correctly matched to the immunodeficiency?

Ataxia–telangiectasia – absent NBT (neutrophil nitroblue tetrazolium) reductiondiseases is correctly matched to the immunodeficiency? Bruton’s disease – impaired phagocytosis

Bruton’s disease – impaired phagocytosisabsent NBT (neutrophil nitroblue tetrazolium) reduction Chronic granulomatous disease (CGD) –

Chronic granulomatous disease (CGD) – hypogammaglobulinaemiaBruton’s disease – impaired phagocytosis Chédiak–Higashi – reduced IgA levels

Chédiak–Higashi – reduced IgA levelsgranulomatous disease (CGD) – hypogammaglobulinaemia DiGeorge syndrome – absent T-cell function

DiGeorge syndrome – absent T-cell functionChédiak–Higashi – reduced IgA levels Ataxia–telangiectasia presents in childhood with

Ataxia–telangiectasia presents in childhood with cerebellar ataxia, impaired cell- mediated immunity and productions of antibody. It is an autosomal-recessive condition. Bruton’s disease is an X-linked hypogammaglobulinaemia due to absent mature B cells. Recurrent pyogenic infections occur once maternal antibody levels fall. CGD (chronic granulomatous disease) is caused by a failure of intracellular killing (no respiratory burst). There are various types and screening for CGD is by the nitroblue tetrazolium (NBT) test. Chédiak–Higashi is a disorder affecting neutrophil chemotaxis and is inherited as an autosomal- recessive. DiGeorge syndrome consists of hypoparathyroidism (hypocalcaemic convulsions in newborns), cardiac anomalies, abnormal facies and absent T-cell function (impaired cell-mediated immunity). In this condition the third and fourth branchial arches, and therefore the thymus and parathyroid, fail to develop. As a result, cardiac outflow tract anomalies occur (interrupted aortic arch, truncus arteriosus and teratology of Fallot). 5

59-You are reviewing an HLA tissue typing result. The sample has been found to be HLA B5-positive on typing.

Which of the following diseases is most closely associated with HLA B5?

Dermatitis herpetiformishas been found to be HLA B5-positive on typing. Which of the following diseases is most

Behçet’s syndromeGrave’s disease Addison’s disease Sjögren’s syndrome The major histocompatibility complex (MHC) is

Grave’s diseaseBehçet’s syndrome Addison’s disease Sjögren’s syndrome The major histocompatibility complex

Addison’s diseaseBehçet’s syndrome Grave’s disease Sjögren’s syndrome The major histocompatibility complex (MHC)

Sjögren’s syndromesyndrome Grave’s disease Addison’s disease The major histocompatibility complex (MHC) is a cluster of

The major histocompatibility complex (MHC) is a cluster of genes located on the short arm of chromosome 6, and it codes for a series of molecules known as the ‘human leucocyte antigens’ (HLA). HLA molecules are distributed throughout the body, and it is through differential HLA expression that cells are classified as ‘self’ or ‘non-self’. Class-I molecules (subtypes A, B and C) are expressed on all cell types except erythrocytes and trophoblasts. They interact with CD8-positive T cells and are involved in driving cytotoxic reactions.

Behçet’s syndrome is associated with HLA B5 positivity, as is polycystic kidney disease and ulcerative colitis. All the other stems mentioned in this question are associated with the B8-DR3 subtype, as are autoimmune hepatitis, idiopathic membranous glomerulonephritis, myasthenia gravis and systemic lupus erythematosus. 2

60-A patient presents with eczema, thrombocytopenia and recurrent infections. What is the most likely diagnosis?

Wiskott–Aldrich syndromeand recurrent infections. What is the most likely diagnosis? Hyper-IgE syndrome Gaucher’s disease IgA deficiency

Hyper-IgE syndromethe most likely diagnosis? Wiskott–Aldrich syndrome Gaucher’s disease IgA deficiency Malignancy

Gaucher’s diseaseWiskott–Aldrich syndrome Hyper-IgE syndrome IgA deficiency Malignancy Wiskott-Aldrich syndrome is an

IgA deficiencysyndrome Hyper-IgE syndrome Gaucher’s disease Malignancy Wiskott-Aldrich syndrome is an X-linked disease,

MalignancyHyper-IgE syndrome Gaucher’s disease IgA deficiency Wiskott-Aldrich syndrome is an X-linked disease,

Wiskott-Aldrich syndrome is an X-linked disease, characterised by eczema, thrombocytopenia and repeated infections and is caused by mutations in the WASP gene. The WASP protein is expressed in cells of all haematopoietic lineages. It may serve a cytoskeletal organising role for signalling elements that are particularly important in platelets and T cells. The platelets are small and have a shortened half-life. Affected male infants often present with bleeding and most do not survive childhood, dying of complications of bleeding, infection or lymphoreticular malignancy. The immunological defects include low serum concentrations of IgM, while IgA and IgG are normal and IgE is frequently

increased. The number and class distribution of B lymphocytes are usually normal.

1

61-A patient presents with facial abnormalities that may include abnormal ears, a shortened philtrum, micrognathia and hypertelorism.

Which cells is this patient lacking?

T lymphocytes

T

lymphocytes

B lymphocytes

B

lymphocytes

Erythrocytes

Erythrocytes

Melanocytes

Melanocytes

Leucocytes

Leucocytes

This classic example of isolated T-cell deficiency results from maldevelopment of thymic epithelial elements derived from the third and fourth pharyngeal pouches. The gene defect has been mapped to chromosome 22q11 in most patients with the DiGeorge syndrome, and to chromosome 10p in others. Signs of defective development of organs dependent on cells of embryonic neural crest origin include: congenital cardiac defects, particularly those involving the great vessels; hypocalcaemic tetany, due to failure of parathyroid development; and absence of a normal thymus. Facial abnormalities may include abnormal ears, a shortened philtrum, micrognathia and hypertelorism. Serum immunoglobulin concentrations are frequently normal, but antibody responses, particularly of IgG and IgA isotypes, are usually impaired. T-cell levels are reduced, whereas B-cell levels are normal. Affected individuals usually have a small, histologically normal thymus located near the base of the tongue or in the neck, allowing most patients to develop functional T cells in numbers that may or may not be adequate for host defence. 1

62-A 16-year-old girl presents to Accident & Emergency with an acute hereditary angioedema involving the larynx.

What is the appropriate immediate management?

Antihistamines

Antihistamines

IV hydrocortisione

IV hydrocortisione

Fresh frozen plasma

Fresh frozen plasma

C1 inhibitor concentrateRecombinant C1 inhibitor This condition is due to deficiency of C1 inhibitor. This causes uncontrolled

Recombinant C1 inhibitorC1 inhibitor concentrate This condition is due to deficiency of C1 inhibitor. This causes uncontrolled activation

This condition is due to deficiency of C1 inhibitor. This causes uncontrolled activation of the classical complement pathway, resulting in angioedema. Patients often present with orofacial swelling, which can cause respiratory obstruction and abdominal pain. They do not usually get urticaria or pruritis (this is not a type-I hypersensitivity reaction) and it does not respond to antihistamines. C4 levels fall during an acute attack, while C3 levels may remain stable. It needs to be treated with the inhibitor, present in fresh frozen plasma or C1 inhibitor concentrate; concentrate is the preferred option. Recombinant preparations are not yet in routine clinical use. 4

63-Immunoglobulin structure – which of the following regions forms the antigen binding site?

The heavy chainof the following regions forms the antigen binding site? The light chain The constant region of

The light chainregions forms the antigen binding site? The heavy chain The constant region of one heavy and

The constant region of one heavy and one light chainthe antigen binding site? The heavy chain The light chain The hinge region The variable region

The hinge regionchain The constant region of one heavy and one light chain The variable region of one

The variable region of one heavy and one light chainregion of one heavy and one light chain The hinge region The immunoglobulin is a Y

The immunoglobulin is a Y shaped molecule that consists of four polypeptide chains. Two chains are heavy and 2 are light. Each heavy and light chain has 2 regions, the constant and variable. The constant region is identical in all antibodies of the same type. The antigen binding site is situated within the variable region of the immunoglobulin structure, made up of both the heavy and light chains, specifically within the hypervariable regions. 5

64-Which immunoglobulin can fix complement via the alternative pathway?

IgAthe hypervariable regions. 5 64- Which immunoglobulin can fix complement via the alternative pathway? IgM IgG

IgMthe hypervariable regions. 5 64- Which immunoglobulin can fix complement via the alternative pathway? IgA IgG

IgGthe hypervariable regions. 5 64- Which immunoglobulin can fix complement via the alternative pathway? IgA IgM

IgEthe hypervariable regions. 5 64- Which immunoglobulin can fix complement via the alternative pathway? IgA IgM

IgDthe hypervariable regions. 5 64- Which immunoglobulin can fix complement via the alternative pathway? IgA IgM

IgA is unusual in that it can fix complement via the alternative pathway. IgG and IgM can fix complement via the classical pathway through the Fc portion of the immunoglobulin. 1

65-Periodic fever can be associated with high levels of:

IgM1 65- Periodic fever can be associated with high levels of: IgG IgA IgE IgD Hyper-IgD

IgGPeriodic fever can be associated with high levels of: IgM IgA IgE IgD Hyper-IgD is associated

IgAfever can be associated with high levels of: IgM IgG IgE IgD Hyper-IgD is associated with

IgEfever can be associated with high levels of: IgM IgG IgA IgD Hyper-IgD is associated with

IgDfever can be associated with high levels of: IgM IgG IgA IgE Hyper-IgD is associated with

Hyper-IgD is associated with attacks of periodic fever every 4–8 weeks, with each attack lasting 3–7 days. Other symptoms and/or signs include abdominal pain, diarrhoea, vomiting, lymphadenopathy, arthralgia or arthritis and skin lesions. IgD levels in periodic fever are raised and range from 145 to 5300 U/ml (normal levels are < 100 U/ml). 5

66-Coeliac disease can be associated with low levels of:

IgM5 66- Coeliac disease can be associated with low levels of: IgG IgA IgE IgD There

IgGCoeliac disease can be associated with low levels of: IgM IgA IgE IgD There is an

IgAdisease can be associated with low levels of: IgM IgG IgE IgD There is an increased

IgEdisease can be associated with low levels of: IgM IgG IgA IgD There is an increased

IgDcan be associated with low levels of: IgM IgG IgA IgE There is an increased incidence

There is an increased incidence of coeliac disease (also known as Gluten Sensitivity Enteropathy (GSE)) in people with selective IgA deficiency. As serological diagnosis of coeliac disease is based on the detection of IgA antibodies to transglutaminase or of anti-endomysial antibody, it is important to check total serum IgA before excluding the diagnosis on the basis of serology. 3

67-A 15-year-old boy presents with fever, rash and arthralgia. He has ++ protein and + blood on urinalysis. Investigations reveal the following:

erythrocyte sedimentation rate 32; C-reactive protein 12; full blood count normal; and U+Es normal. Antistreptolysin-O titres are raised.

What immunological phenomenon is taking place?

Type-I hypersensitivity reactionType-II hypersensitivity reaction Type-III hypersensitivity reaction Type-IV hypersensitivity reaction Cryoglobulinaemia

Type-II hypersensitivity reactionType-I hypersensitivity reaction Type-III hypersensitivity reaction Type-IV hypersensitivity reaction Cryoglobulinaemia He

Type-III hypersensitivity reactionhypersensitivity reaction Type-II hypersensitivity reaction Type-IV hypersensitivity reaction Cryoglobulinaemia He has a

Type-IV hypersensitivity reactionhypersensitivity reaction Type-III hypersensitivity reaction Cryoglobulinaemia He has a poststreptococcal

Cryoglobulinaemiahypersensitivity reaction Type-IV hypersensitivity reaction He has a poststreptococcal glomerulonephritis, an immune

He has a poststreptococcal glomerulonephritis, an immune complex disease, which is a type 3 hypersensitivity reaction. Other infectious causes of immune complex disease include hepatitis B and C, cytomegalovirus and malaria. 3

68-A 13-year-old boy has suffered from recurrent sinus infections for the past 2 years and has a history of intermittent diarrhoea. He has a family history of autoimmune disease – his mother has coeliac disease and sister autoimmune haemolytic anaemia. His full blood count is normal.

What is his most likely diagnosis?

Coeliac diseaseblood count is normal. What is his most likely diagnosis? Systemic lupus erythematosus Selective IgA deficiency

Systemic lupus erythematosusnormal. What is his most likely diagnosis? Coeliac disease Selective IgA deficiency Common variable immunodeficiency

Selective IgA deficiencydiagnosis? Coeliac disease Systemic lupus erythematosus Common variable immunodeficiency Wiskott–Aldrich

Common variable immunodeficiencySystemic lupus erythematosus Selective IgA deficiency Wiskott–Aldrich syndrome This boy most likely has

Wiskott–Aldrich syndromeSelective IgA deficiency Common variable immunodeficiency This boy most likely has common variable immune deficiency.

This boy most likely has common variable immune deficiency. The history of invasive infection and gut involvement and the family history of immune cytopaenia are suggestive. Selective IgA deficiency, although more common, is often asymptomatic but it can also be associated with autoimmune disease. 4

69-An HIV positive child develops Pneumocystis jiroveci pneumonia. He is deficient of what immunological component?

Complement

Complement

T cells

T

cells

B cells

B

cells

IgM

IgM

IgAPatients with HIV have a deficiency of CD4 lymphocytes which are also known as helper

Patients with HIV have a deficiency of CD4 lymphocytes which are also known as helper T cells. They are involved with antigen specific responses as well as delayed type hypersensitivity. The risk of developing P. jiroveci pneumonia is greatest with a CD4 count of 200 x 10 9 /l or below. 2

70-A young boy has his second episode of Neisseria meningitis.

What is he deficient in?

C1episode of Neisseria meningitis. What is he deficient in? C2 C3 C4 C5 Opportunistic bacterial infections,

C2of Neisseria meningitis. What is he deficient in? C1 C3 C4 C5 Opportunistic bacterial infections, such

C3of Neisseria meningitis. What is he deficient in? C1 C2 C4 C5 Opportunistic bacterial infections, such

C4of Neisseria meningitis. What is he deficient in? C1 C2 C3 C5 Opportunistic bacterial infections, such

C5Neisseria meningitis. What is he deficient in? C1 C2 C3 C4 Opportunistic bacterial infections, such as

Opportunistic bacterial infections, such as meningococcus and gonorrhoea, occur because of defects in the lytic complement pathway (C5–C9). The complement system comprises a series of glycoproteins that are activated as part of a cascade sequence. Activation of this cascade eventually leads to assembly of components C5–C9 of the complement system. These form the membrane attack complex (MAC), which forms a transmembrane channel that causes cell lysis by osmotic shock. The pathway may be activated in a classic way, by antigen–antibody immune complexes, apoptotic cells, C-reactive protein (CRP) bound to ligand, and certain viruses and bacteria, or in an alternative way by bacterial endotoxin, fungal cell walls, viruses, and certain tumour cells. Deficiencies of C3, C1q or factors H or I lead to increased susceptibility to infection with capsulated bacteria. 5

71-Cells from a patient with severe combined immunodeficiency disease (SCID) lack the adenosine deaminase enzyme.

This will have a direct effect on:

Synthesis of deoxynucleoside diphosphates (dNDPs)the adenosine deaminase enzyme. This will have a direct effect on: Degradation of guanine nucleotides Purine

Degradation of guanine nucleotidesdeaminase enzyme. This will have a direct effect on: Synthesis of deoxynucleoside diphosphates (dNDPs) Purine salvage

Purine salvageThis will have a direct effect on: Synthesis of deoxynucleoside diphosphates (dNDPs) Degradation of guanine nucleotides

De novo synthesis of purine nucleotides synthesis of purine nucleotides

Degradation of adenine nucleotidesDe novo synthesis of purine nucleotides Lymphocytes need efficient salvage and interconversion pathways for purines and

Lymphocytes need efficient salvage and interconversion pathways for purines and pyrimidines during rapid bursts of proliferation, particularly in the lymphoid germinal centres and fetal thymus. Adenosine deaminase (ADA) deficiency was the first established cause of severe combined immunodeficiency disease (SCID), the condition also being the first example of enzyme replacement therapy (initially using red cell transfusions which contain ADA) in clinical medicine, and later being the first disease to be treated by gene therapy, although with only partial success. ADA has an important role in the intermediate pathways of purine metabolism. Purine-nucleoside phosphorylase (PNP) is also active in this pathway, but is a much rarer cause of SCID. It is interesting that deficiencies in both these enzymes predominantly affect lymphocytes, despite their presence in most other cells of the body. 3

72-Deranged cellular immunity:

Often presents with severe viral infections

Is

associated with DiGeorge syndrome

Is

associated with gram positive severe infections

Is

associated with prematurity

Occurs in agammaglobulinaemia

Cell mediated immunity is mediated by T-cells and has, as one of it’s major roles, the control of viral infections. Abnormalities of cell mediated immunity occur in DiGeorge syndrome because of the absence of T-cell maturation secondary to thymic abnormalities. Protection from bacterial infection is classically associated with B-cell abnormalities and the consequent inability to

produce antibodies although such clear cut distinctions are slightly artificial. Prematurity is associated with immaturity of the immune system but this mainly manifests as abnormal antibody production. X-linked agammaglobulinaemia is a pure B-cell defect and affected children have normal cell mediated immunity.

T T F F F

73-A boy was born at 26 weeks gestation. He had severe hyaline membrane disease and was ventilated for 3 weeks. He is now three months old and has just been discharged from hospital. He should receive pertussis vaccination even if:

His Apgar scores were 3 at 1, and 5 at 5 minutes

He had a pneumothorax and 4 convulsions in the first week

He was hypoglycaemic and very jittery for a short period

After a pneumothorax, a cranial ultrasound scan showed an intraventricular haemorrhage with some loss of cerebral substance

He continues to have uncontrolled convulsions two or three times a week

Children with cerebral damage, a personal history of convulsions, or a family history of febrile convulsions are at increased risk of a febrile fit following pertussis and measles immunisation. However, these are not absolute contraindications and they are not at any greater risk of permanent adverse effects from the vaccines and should receive them. Children whose epilepsy is poorly controlled should not be immunised until control is achieved, although convulsions themselves are not a contraindication.

The only absolute contraindications for pertussis-containing vaccines are:

Confirmed anaphylactic reaction to a previous dose of pertussis-containing vaccine, or

Confirmed anaphylactic reaction to neomycin, streptomycin or polymyxin B

(which may be present in trace amounts in the vaccine).

74-The following are live vaccines

T T T T F

BCG

Measles

Oral polio

Pertussis

Rubella

IM (Salk) polio vaccine is inactivated, while oral polio is an activated live vaccine. The pertussis vaccine is acellular and made from part of the pertussis cell.

T T T F T

75-With regard to the Measles, Mumps and Rubella (MMR) vaccine:

It

should not be given if there is a history of previous measles infection

It

should not be given if there has been a previous measles immunisation

It

is contraindicated in a child on oral corticosteroids

It

is contraindicated where there is a personal history of febrile convulsions

It

is contraindicated if there is a family history of epilepsy

Live vaccine is contraindicated in children who may be immunosuppressed (such as oral steroids). Steroids, such as prednisolone, given to children either orally or rectally at a daily dose of 2mg/kg/day for at least one week or 1mg/kg/day for one month should be deemed as a contraindication and administration of live vaccines should be postponed for at least 3 months after immunosuppressive treatment has stopped.

Previous infection or immunisation is not a contraindication, and 2 MMR doses are recommended. A fit within 72 hours of a previous dose would be a

contraindication, although febrile convulsions and a family history of epilepsy are

not.

F F T F F

76-Which of the following pathogens are associated with the accompanying immune disorder?

Mycobacterium and cellular immunity

Gram -ve bacteria and complement deficiency

Enterovirus and antibody defects

Staphylococcus and complement deficiency

Haemophilus influenzae and neutrophil defect

The pathogens associated with an underlying immune disorder are:

Mycobacterium – cellular immunity

Gram -ve and Gram +ve bacteria – neutrophil defects

Enterovirus – antibody defects

Staphylococcus – complement deficiency

Neisseria – complement deficiency

Haemophilus influenzae – antibody defects

Salmonella – type 1 cytokine defects and cell-mediated defects

Mycoplasma – antibody defects

Herpes virus – defects in cell-mediated immunity.

T F T T F

77-Which of the following statements regarding chronic cutaneous candidiasis are true?

It is associated with poor T-cell function

It can be successfully treated with bone marrow transplantation

It is totally eradicated with fluconazole

It can cause failure to gain weight in infancy

It may be associated with an endocrinopathy in adult life

The exact underlying defect in chronic cutaneous candidiasis is still poorly understood; there is, however, poor T-cell proliferation and cytokine production. There is persistent Candida infection, which is recurrent and not eliminated by antifungal treatment. Oesophageal involvement can lead to gastro-oesophageal reflux and dropping off the weight centiles. In over 50% of cases, there is, in the second to third decade of life, an endocrinopathy that may involve combinations of hypoparathyroidism, Addison’s disease, pernicious anaemia, hypothyroidism

and diabetes mellitus.

T T F T T

78-Which of the following children should not receive live vaccines?

Those requiring regular intravenous immunoglobulin therapy

Those on a prednisolone dose of 3 mg/kg per day for longer than 1 week

Children with graft-versus-host disease

Children on chemotherapy

Children who have had a solid organ transplant

Intravenous immunoglobulin treatment will negate the live virus. The other categories bestow vulnerability and could lead to evolution of the disease. Post- transplant children are maintained on lifelong immunosuppression. 4 T

79-In which of the following diseases should a complement abnormality be suspected?

Recurrent folliculitis

Pneumocystis carinii infection

Recurrent swelling after trauma

Delayed separation of the cord

Pancreatitis

A decreased C3 level is seen in:

Systemic lupus erythematosus (antinuclear antibodies (ANA), antidouble- stranded DNA)

Mesangiocapillary glomerulonephritis

Membranoproliferative glomerulonephritis (type 2)

Post-streptococcal glomerulonephritis

Infective endocarditis

Infected ventricular shunts

Chronic Gram-negative infection.

Increased complement activation is seen in:

Hereditary angioneurotic oedema (C1 inhibitor deficiency)

Pregnancy

Paroxysmal nocturnal haemoglobinuria

Glomerulonephritis grade 2.

The level is not changed in focal sclerosis, focal segmental glomerulonephritis, Henoch–Schönlein purpura or haemolytic-uraemic syndrome.

A defect in the complement system should be suspected in:

Focal swelling after trauma

Recurrent meningococcal infection (C5–C9) (encapsulated organisms)

Recurrent staphylococcal infection

Lupus-like syndrome (major histocompatibility complex, chromosome 6).

Complement abnormality is not suspected in recurrent folliculitis, Pneumocystis carinii infection (combined immunodeficiency) or delayed separation of the cord

(leukocyte adhesion defect), or inherent complement deficiency in membranoproliferative disorders. Pancreatitis involves the consumption of normal levels of complement. F F T F F

80-This substance is derived from arachidonic acid. The arachidonic acid is cleaved into cyclooxygenase derivatives and lipoxygenase derivatives. This substance is produced by the latter and is synthesised by leukocytes and mast cells. Leukocytes and mast cells are mediators of inflammation and allergic reactions by increasing chemotaxis and vascular permeability and inducing smooth muscle constriction. They also cause arteriolar constriction and bronchoconstriction.

What is the substance?

Thromboxaneconstriction and bronchoconstriction. What is the substance? Prostacyclin Prostaglandin Leukotriene Eosinophil

Prostacyclinand bronchoconstriction. What is the substance? Thromboxane Prostaglandin Leukotriene Eosinophil Leukotrienes are

ProstaglandinWhat is the substance? Thromboxane Prostacyclin Leukotriene Eosinophil Leukotrienes are synthesised by

Leukotrieneis the substance? Thromboxane Prostacyclin Prostaglandin Eosinophil Leukotrienes are synthesised by leukocytes and

EosinophilThromboxane Prostacyclin Prostaglandin Leukotriene Leukotrienes are synthesised by leukocytes and mast cells.

Leukotrienes are synthesised by leukocytes and mast cells. They mediate inflammation and allergic reactions in the following ways:

By increasing neutrophil/eosinophil chemotaxis and vascular permeability, and inducing smooth muscle constriction

By causing arteriolar constriction and bronchoconstriction.

Leukotriene D4 is identified as the slow-reacting substance of anaphylaxis (SRS- A) and is responsible for smooth muscle contraction. Leukotrienes are derived from arachidonic acid and not palmitic acid. The arachidonic acid is cleaved into cyclooxygenase derivatives, which produce prostaglandins, prostacyclins and thromboxanes. The other pathway produces leukotrienes. Leukotrienes do not act synergistically with SRS-A as leukotrienes are produced by mast cells to dampen the inflammatory response and decrease granulocyte formation at the site of invasion. 4

81-An 18-month-old male presents with recurrent pneumonia, ear infections and tonsillitis. The family history includes a previous male infant death at 2 years of age from pneumococcal meningitis. The parents are therefore very concerned and wish further investigations to be carried out.

After the results have returned, it is found that the child has absent or decreased levels of immunoglobulins A, G and M. He has reduced responses to blood group antibodies to immunisations and an increased percentage of E rosettes with red blood cells. His PHA and nitroblue tetrazolium (NBT) tests are normal.

The following differential diagnosis may be considered, but the ultimate disorder is which of the following?

Common variable immune deficiencybut the ultimate disorder is which of the following? X-linked agammaglobulinaemia Chronic granulomatous disease

X-linked agammaglobulinaemiais which of the following? Common variable immune deficiency Chronic granulomatous disease Severe combined

Chronic granulomatous diseasevariable immune deficiency X-linked agammaglobulinaemia Severe combined immunodeficiency syndrome

Severe combined immunodeficiency syndromeX-linked agammaglobulinaemia Chronic granulomatous disease Chédiak–Higashi syndrome X-linked

Chédiak–Higashi syndromedisease Severe combined immunodeficiency syndrome X-linked agammaglobulinaemia is the most common

X-linked agammaglobulinaemia is the most common immunoglobulin deficiency. The gene is localised to the long arm of the X chromosome, with the abnormality being in the gene for the B-cell tyrosine kinase. It is more common in males. This disorder is associated with an increased risk of blood malignancies. It presents after 3–6 months of age when the level of IgG resulting from in utero placental transfer has decreased. The child presents with recurrent bacterial infections in the first 2 years of life, namely lung and sinus infections. Prenatal diagnosis is possible. Bone marrow transplantation is carried out if medical interventions fail. 2

82-A 4-year-old, fair-haired, fair-skinned child presents to the outpatient department with a history of recurrent chest infections, ataxia and muscle weakness. He has a long history of fatigue and malaise, and a GP has wondered whether he suffers from infectious mononucleosis. He is currently on sodium valproate for seizures, which have been observed since the age of 2 years. On examination, he has bilateral nystagmus, photophobia and an increased red light reflex. He shows signs of sensory and motor neuropathy, and marked muscle weakness.

Which of the following is the most likely informative investigation to be undertaken?

Full blood countthe most likely informative investigation to be undertaken? Clotting profile Bacterial and viral serology Chromosomal

Clotting profileinformative investigation to be undertaken? Full blood count Bacterial and viral serology Chromosomal studies White cell

Bacterial and viral serologyto be undertaken? Full blood count Clotting profile Chromosomal studies White cell count and natural killer

Chromosomal studiesblood count Clotting profile Bacterial and viral serology White cell count and natural killer cell function

White cell count and natural killer cell function testsprofile Bacterial and viral serology Chromosomal studies Investigations depict a decreased antibody-dependent

Investigations depict a decreased antibody-dependent cell-mediated cytolysis of the tumour-like reaction. There is decreased function of natural killer cells, a prolonged bleeding time, impaired platelet aggregation, decreased neutrophil number and a pancytopenia when associated with bacterial and viral illnesses.

The suspected diagnosis here is Chediak Higashi syndrome. Affected children present with ataxia, seizures, muscle weakness and an illness similar in picture to lymphoma with lymphotropic viruses, e.g. Epstein Barr virus. Ocular symptoms include nystagmus photophobia and an increased red reflex. 5

83-A 4-year-old, fair-haired, fair-skinned child presents to the outpatient department with a history of recurrent chest infections, ataxia and muscle weakness. He has a long history of fatigue and malaise, and a GP has wondered whether he suffers from infectious mononucleosis. He is currently on sodium valproate for seizures, which have been observed since the age of 2 years. On examination, he has bilateral nystagmus, photophobia and an increased red light reflex. He shows signs of sensory and motor neuropathy, and marked muscle weakness.

What is the most probable diagnosis?

Wilms’ tumourmarked muscle weakness. What is the most probable diagnosis? Chédiak–Higashi syndrome Infectious mononucleosis

Chédiak–Higashi syndromeWhat is the most probable diagnosis? Wilms’ tumour Infectious mononucleosis Epstein–Barr virus-driven

Infectious mononucleosisWilms’ tumour Chédiak–Higashi syndrome Epstein–Barr virus-driven Burkitt’s lymphoma

Epstein–Barr virus-driven Burkitt’s lymphomaWilms’ tumour Chédiak–Higashi syndrome Infectious mononucleosis Guillain–Barré syndrome 47

Guillain–Barré syndromeChédiak–Higashi syndrome Infectious mononucleosis Epstein–Barr virus-driven Burkitt’s lymphoma 47

This autosomal recessive disorder occurs due to dysfunctional and reduced natural killer cells. Pathologically, the leukocytes contain giant cytoplasmic granules. Other cells can also contain these granules, giving features of the disease. Melanocytes do not, however, disperse pigments within the cells; hence there are features of partial albinism. There are no hyperpigmented lesions of the lumbosacral area. Schwann cells are affected, causing sensory and motor neuropathies. People with this disorder have an increased susceptibility to infections due to defective chemotaxis, degranulation and bactericidal activity of the neutrophils. There is an increased incidence of malignancies and a high mortality rate with respect to infection.

Affected children present with ataxia, seizures, muscle weakness and an illness similar in picture to lymphoma with lymphotrophic viruses, e.g. Epstein–Barr virus. Ocular symptoms include nystagmus, photophobia and an increased red reflex. 2

84-A 4-month-old male infant is referred with a chronic history of superficial skin abscesses and painful lymphadenopathy. Routine investigations reveal chronic anaemia and neutrophilia with a raised erythrocyte sedimentation rate, and Grampositive cocci have grown in a pus sample obtained from a perianal abscess 4 weeks previously. On examination, you find a pale child with a marked swelling of the left submandibular region. He has reduced air entry with crepitations at the left lower lobe consistent with a left lower lobe pneumonia. Abdominal examination reveals hepatomegaly and previous scarring from peri-anal abscesses. Routine sputum and stool samples are sent from the clinic, which reveal that he has grown Serratia marcescens from his sputum sample. He has had Salmonella infection in the previous 3 months.

Which is the most informative investigation to consider?

Immunoglobulin levelsWhich is the most informative investigation to consider? Skin biopsy of an abscess lesion Nitroblue tetrazolium

Skin biopsy of an abscess lesioninformative investigation to consider? Immunoglobulin levels Nitroblue tetrazolium (NBT) test Clotting screen Neutrophil

Nitroblue tetrazolium (NBT) testImmunoglobulin levels Skin biopsy of an abscess lesion Clotting screen Neutrophil function test Chronic

Clotting screenbiopsy of an abscess lesion Nitroblue tetrazolium (NBT) test Neutrophil function test Chronic granulomatous disease may

Neutrophil function testlesion Nitroblue tetrazolium (NBT) test Clotting screen Chronic granulomatous disease may manifest soon after birth

Chronic granulomatous disease may manifest soon after birth with superficial skin sepsis and painful regional lymphadenopathy. Lesions heal incompletely with sinus formation. Due to the inability to kill catalasepositive micro-organisms,

chronic deep infections occur, and common recurrent skin abscesses with Staphylococcus, Escherichia coli, Serratia, Klebsiella and Candida may be seen. Less common infections include those involving Shigella, Salmonella and Pseudomonas.

In the NBT test the colourless nitroblue tetrazolium is reduced to blue formazan by the activity of the phagocyte oxidase (phox) enzyme system. Flow cytometry can provide quantification of the activity in the cells. A negative NBT test (remains colourless) may confirm the diagnosis of chronic granulomatous disease. 3

85-A 4-month-old male infant is referred with a chronic history of superficial skin abscesses and painful lymphadenopathy. Routine investigations reveal chronic anaemia and neutrophilia with a raised erythrocyte sedimentation rate, and Grampositive cocci have grown in a pus sample obtained from a perianal abscess 4 weeks previously. On examination, you find a pale child with a marked swelling of the left submandibular region. He has reduced air entry with crepitations at the left lower lobe consistent with a left lower lobe pneumonia. Abdominal examination reveals hepatomegaly and previous scarring from peri-anal abscesses. Routine sputum and stool samples are sent from the clinic, which reveal that he has grown Serratia marcescens from his sputum sample. He has had Salmonella infection in the previous 3 months. You have instigated a Nitroblue tetrazolium (NBT) test.

The diagnosis is which of the following?

Chédiak–Higashi syndrome(NBT) test. The diagnosis is which of the following? Chronic granulomatous disease Lactoferrin deficiency

Chronic granulomatous diseasewhich of the following? Chédiak–Higashi syndrome Lactoferrin deficiency Shwachman syndrome Systemic lupus

Lactoferrin deficiencysyndrome Chronic granulomatous disease Shwachman syndrome Systemic lupus erythematosus Chronic

Shwachman syndromeChronic granulomatous disease Lactoferrin deficiency Systemic lupus erythematosus Chronic granulomatous disease

Systemic lupus erythematosusdisease Lactoferrin deficiency Shwachman syndrome Chronic granulomatous disease may manifest soon after birth

Chronic granulomatous disease may manifest soon after birth with superficial skin sepsis and painful regional lymphadenopathy. Lesions heal incompletely with sinus formation. Due to the inability to kill catalasepositive micro-organisms, chronic deep infections occur, and common recurrent skin abscesses with Staphylococcus, Escherichia coli, Serratia, Klebsiella and Candida may be seen. Less common infections include those involving Shigella, Salmonella and Pseudomonas.

All these pathogens display a lack of oxidative respiratory burst and produce oxygen free radicals. The neutrophil is unable to activate one or more oxidases to consume oxygen to produce superoxide or hydrogen peroxide following phagocytosis. Superoxide stimulates the hexose monophosphate shunt, and halides are produced. The interaction of reactive oxygen molecules, myeloperoxidase and halides with phagocytic vacuoles results in the effective killing of catalase- containing bacteria. Gram-negative rods and catalase-negative organisms are killed normally as they generate hydrogen peroxide. Aspergillus is a common secondary pathogen, but herpesvirus is not found as a pathogen.

Other clinical manifestations include respiratory tract infections, sinusitis, urinary tract infections, obstructive uropathy and liver infections (abscesses) with hepatosplenomegaly. Gastrointestinal involvement includes necrotic granulomas, colitis, oesophageal strictures, perinatal abscess and pyloric strictures. Chronic osteomyelitis of the small bones of the hands and feet may be difficult to treat.

The differential diagnosis includes neutrophil-killing defects, Chédiak–Higashi syndrome, lactoferrin deficiency, mobility disorders such as lazy leukocyte syndrome and Shwachman syndrome. Chronic illnesses, including systemic lupus erythematosus, rheumatoid arthritis, tuberculosis, toxoplasmosis, hyper-IgE syndrome and malnutrition, may also be associated. 2

86-A 4-month-old male infant is referred with a chronic history of superficial skin abscesses and painful lymphadenopathy. Routine investigations reveal chronic anaemia and neutrophilia with a raised erythrocyte sedimentation rate, and Grampositive cocci have grown in a pus sample obtained from a perianal abscess 4 weeks previously. On examination, you find a pale child with a marked swelling of the left submandibular region. He has reduced air entry with crepitations at the left lower lobe consistent with a left lower lobe pneumonia. Abdominal examination reveals hepatomegaly and previous scarring from peri-anal abscesses. Routine sputum and stool samples are sent from the clinic, which reveal that he has grown Serratia marcescens from his sputum sample. He has had Salmonella infection in the previous 3 months.

After a Nitroblue tetrazolium (NBT) test, the diagnosis has been confirmed as chronic granulomatous disease.

Appropriate management on discharge may be which of the following?

Prophylactic antibioticsAmphotericin White cell and granulocyte infusions Interferon- γ infusions All of the above Chronic granulomatous

AmphotericinProphylactic antibiotics White cell and granulocyte infusions Interferon- γ infusions All of the above Chronic

White cell and granulocyte infusionsProphylactic antibiotics Amphotericin Interferon- γ infusions All of the above Chronic granulomatous disease may manifest

Interferon-γ infusions γ infusions

All of the abovecell and granulocyte infusions Interferon- γ infusions Chronic granulomatous disease may manifest soon after birth

Chronic granulomatous disease may manifest soon after birth with superficial skin sepsis and painful regional lymphadenopathy. Lesions heal incompletely with sinus formation. Due to the inability to kill catalasepositive micro-organisms, chronic deep infections occur, and common recurrent skin abscesses with Staphylococcus, Escherichia coli, Serratia, Klebsiella and Candida may be seen. Less common infections include those involving Shigella, Salmonella and Pseudomonas.

Antimicrobial prophylaxis along with early and aggressive treatment of infections are the basis of treatment, with interferon used in acute infection (commonly used daily in the US but in Europe is not used routinely due to expense). 5

87-A 4-month-old male infant is referred with a chronic history of superficial skin abscesses and painful lymphadenopathy. Routine investigations reveal chronic anaemia and neutrophilia with a raised erythrocyte sedimentation rate, and Grampositive cocci have grown in a pus sample obtained from a perianal abscess 4 weeks previously. On examination, you find a pale child with a marked swelling of the left submandibular region. He has reduced air entry with crepitations at the left lower lobe consistent with a left lower lobe pneumonia. Abdominal examination reveals hepatomegaly and previous scarring from peri-anal abscesses. Routine sputum and stool samples are sent from the clinic, which reveal that he has grown Serratia marcescens from his sputum sample. He has had Salmonella infection in the previous 3 months. After investigation, the diagnosis has been confirmed as chronic granulomatous disease.What is the pattern of inheritance?

Autosomal dominance inheritance

Autosomal recessive inheritance

X-linked recessive inheritance

X-linked dominant inheritance

Co-dominant inheritance

Chronic granulomatous disease may manifest soon after birth with superficial skin sepsis and painful regional lymphadenopathy. Lesions heal incompletely with sinus formation. Due to the inability to kill catalasepositive micro-organisms, chronic deep infections occur, and common recurrent skin abscesses with Staphylococcus, Escherichia coli, Serratia, Klebsiella and Candida may be seen. Less common infections include those involving Shigella, Salmonella and Pseudomonas. All these pathogens display a lack of oxidative respiratory burst and produce oxygen free radicals. The neutrophil is unable to activate one or more oxidases to consume oxygen to produce superoxide or hydrogen peroxide following phagocytosis. Superoxide stimulates the hexose monophosphate shunt, and halides are produced. The interaction of reactive oxygen molecules, myeloperoxidase and halides with phagocytic vacuoles results in the effective killing of catalase-containing bacteria. Gram-negative rods and catalase-negative organisms are killed normally as they generate hydrogen peroxide. Aspergillus is a common secondary pathogen, but herpesvirus is not found as a pathogen. Other clinical manifestations include respiratory tract infections, sinusitis, urinary tract infections, obstructive uropathy and liver infections (abscesses) with hepatosplenomegaly. Gastrointestinal involvement includes necrotic granulomas, colitis, oesophageal strictures, perinatal abscess and pyloric strictures. Chronic osteomyelitis of the small bones of the hands and feet may be difficult to treat. The differential diagnosis includes neutrophil-killing defects, Chédiak–Higashi syndrome, lactoferrin deficiency, mobility disorders such as lazy leukocyte syndrome and Shwachman syndrome. Chronic illnesses, including systemic lupus erythematosus, rheumatoid arthritis, tuberculosis, toxoplasmosis, hyper-IgE syndrome and malnutrition, may also be associated. F T T F F

88-A 15-year-old girl presents to the outpatient clinic with a chronic history of abdominal pain at the time of her menstrual cycle. Her parents have wondered whether she has been in contact with any environmental pollens or grasses, as at times she has a hoarse voice and her skin comes out in mild oedematous swellings. The parents feel that this could be a psychosomatic element, as it often occurs at times of illness, stress and cold. On examination, there is no fever, rash, arthropathy or oedema. Cardiovascular, respiratory and abdominal examination is unremarkable.

A possible diagnosis could be which of the following?

Idiopathic chronic urticariaexamination is unremarkable. A possible diagnosis could be which of the following? Systemic lupus erythematosus 52

Systemic lupus erythematosusexamination is unremarkable. A possible diagnosis could be which of the following? Idiopathic chronic urticaria 52

Autoimmune Henoch–Schönlein purpuraKawasaki’s disease Hereditary angioneurotic oedema Hereditary angioneurotic oedema is caused by a deficiency or a

Kawasaki’s diseaseAutoimmune Henoch–Schönlein purpura Hereditary angioneurotic oedema Hereditary angioneurotic oedema is caused by

Hereditary angioneurotic oedemaHenoch–Schönlein purpura Kawasaki’s disease Hereditary angioneurotic oedema is caused by a deficiency or

Hereditary angioneurotic oedema is caused by a deficiency or a defect in C1 esterase inhibitor protein, the amount found being <25% the normal value. The protein modulates the intravascular activation of complement, and its deficiency leads to angioedema. There is an inability to synthesise normally functioning C1 inhibitor. The condition is genetically inherited in an autosomal dominant fashion. This disorder usually presents in late childhood or adolescence, ie aged 10–20, when attacks become more frequent. Hereditary angioneurotic oedema causes 2% of all angioedemas. It is found that 85% of individuals have very low levels of inhibitor and 15% have normal or raised non-functioning protein; this may therefore be used in a functional assay. This disorder involves the deeper layers of the skin. Clinically, hereditary angioneurotic oedema presents with:

Abdominal pain and cramps due to swelling of the intestinal tissues secondary to visceral oedema

Subcutaneous oedema and swelling (72 hours maximum)

Laryngeal oedema (presenting as a hoarse voice and sometimes causing fatal obstruction); these may be unresponsive to antihistamines

Symptoms related to phases of the menstrual cycle

Triggers including a prodromal rash, skin trauma (as the protein involved is within the fibrin cascade), menstruation and emotional stress. There is no urticarial rash or inflammation suggestive of pruritus.

Investigations

During an attack, C4 and C2 levels are decreased. There is an excessive stimulation of C2, C4 and related vasopeptides, due to uninhibited activity of complement. The deficiency of C1 inhibitor permits C1 to continuously cleave its substrates C4 and C2 to cause them to become deficient. The C1 and C3 levels are normal, as is the number of B cells. C2b splits off to become the vasoactive component.

Treatment

Treatment used to date includes anabolic steroids, to increase protein levels. This prevents acute attacks, and the symptoms resolve in 2–3 days. Fresh frozen plasma and C1 esterase concentrate are used in the acute phase to restore normal

levels of inhibitor. Androgen agonists, ie danazol or stanozolol, are used in the chronic phase. The side-effects of danazol include androgenic problems in childhood. Other drugs used include alpha-aminocaproic acid and tranexamic acid. Steroids, adrenaline and antihistamines are not effective. 5

89-Theme: Complement receptor abnormalities

A CR3 complement receptor

B Alternative pathway (C5, C6, C7, C8, C9)

C C1 esterase inhibitor

D Decrease in complement receptor (CR2)

E Alternative pathway (C3 convertases)

F Alternative pathway (delay accelerating factor (DAF))

G Classical pathway (C234)

H Classical pathway, mannose-binding lectin

I C1Q, C1R, C2, C3, C4

J Properdin

Match the complement abnormalities above to the following diseases:

Scenario 1 Pyogenic bacterial infection

CR3 complement receptor

Correct answer

Scenario 2 Glomerulonephritis-associated systemic lupus erythematosus (SLE)

C1Q, C1R, C2, C3, C4

Correct answer

Scenario 3 Recurrent neisserial infection

Alternative pathway (C5, C6, C7, C8, C9)

Correct answer

Scenario 4 Non-recurrent neisserial infection

Properdin

Correct answer

Scenario 5 Susceptibility to infection

Classical pathway, mannose-binding lectin

Correct answer

Scenario 6 Hereditary angioneurotic oedema

C1 esterase inhibitor

Correct answer

Scenario 7 Recurrent pyogenic infections

CR3 complement receptor

Correct answer

Scenario 8 Renal diseases

Alternative pathway (C3 convertases)

Correct answer

Scenario 9 Paroxysmal nocturnal haemoglobinuria

Alternative pathway (delay accelerating factor (DAF))

Scenario 10 Pyogenic infections

Correct answer

Decrease in complement receptor (CR2)

Correct answer

The following table summarises the complement proteins and the diseases with which they are associated.

Pathway

Complement protein

Disease(s)

Classical

C1q, C1R, C2, C4

SLE, glomerulonephritis

Alternative

D

Recurrent neisserial infections

 

Properdin

Non-recurrent meningococcal infections

Lectin

Mannose-binding lectin (MBL)

Susceptibility to infections (otitis media)

C3 deficiency

C3, factor I, factor H

SLE, severe infections, glomerulonephritis

syndrome

Membrane

 

Recurrent neisserial infections

attack

C5, C6, C7, C8, C9

Complex control proteins

C1 inhibitor, delay accelerating factor (DAF), homologous restriction factor (HRF)

Hereditary angioneurotic oedema

Complement

CR3

Recurrent pyogenic infections

receptor

C1 activity is increased in C1 inhibitor deficiency. C3a, C4a and C5a all have the ability to bind to mast cells and leukocytes to trigger the release of histamine and mediators. They are involved in anaphylaxis, vasodilatation, swelling and inflammation, bee-sting anaphylaxis and extrinsic allergic alveolitis. C5a is a potent neutrophil chemotactic agent that promotes macrophages to CR1 and CR3 receptors to neutralise. C3a mediates the suppression of antibody responses. C3b enhances cellmediated toxicity and solubilisation of the immune complexes. Low C3 and CH50 levels correlate strongly with a very poor outcome in patients with multiorgan failure. C5b enhances the antibody response involved in the chemotaxis of neutrophils, monocytes and eosinophils. Individuals with a deficiency of C5 are at an increased risk of developing meningococcal sepsis.

The membrane attack complex (C5–C9)

The membrane attack complex (MAC) assembles following the cleavage of C5 to form C5b via the classical or alternative pathway. It inserts into cell membranes to form a channel that traverses the membrane and leads to cell lysis. Its binding to cells is inhibited by very low-density lipoprotein, and autologous cells contain membrane control proteins that partially protect them from the action of MAC. MAC is active only against autologous cells. Paroxysmal nocturnal haemoglobinuria is caused by a decreased number of control membrane proteins so there is an increased sensitivity to MAC.

Complement receptors

These receptors participate in various functions of the host defence system, including the C1 and C4 neutralisation of viruses. There are four complement receptors:

CR1: found in leukocytes in tissues and the circulation. It has a role in immune complex handling and is decreased in SLE as an acquired defect.

CR2: important in the lymphocyte reaction with other cells. Epstein–Barr virus may act as a ligand.

CR3 and CR4: form a receptor that also includes IFA-1 (a lymphocyte receptor). If the level of this receptor is decreased, pyogenic infection results as the neutrophils are unable to bind the bacteria coated in C3. Cryoglobulinaemia displays a low C4 but a normal C3 level.

90-Theme: Human leukocyte antigens

A HLA DR2/W2, DR/W2, B8

B HLA DR3

C HLA DQW2, DR3/7

D HLA A28

E HLA B5

F HLA B27

G HLA DR5

H HLA A3/B14

I HLA B8/DR3

J HLA DR4

Scenario 1 Which of the above HLA associations is responsible for ankylosing spondylitis, psoriatic arthropathy, Reiter’s disease and reactive arthritis? This reactive arthritis may occur after a gut infection with Salmonella, Shigella, Yersinia enterocolitica or Campylobacter and thus presents with bloody diarrhoea.

HLA B27

Correct answer

Scenario 2 Which of the above HLA associations is responsible for Behçet’s disease and the arthritis of inflammatory bowel disease? Ten per cent of suffers of inflammatory bowel disease present with arthritis, and some therefore have associated ankylosing spondylitis.

HLA B5

Correct answer

Scenario 3 Which of the above HLA associations would be suggestive in a 3-year old child who has been weaned on to a gluten-containing diet and subsequently suffers from abdominal protrusion, buttock-wasting and steatorrhoea, and presents with positive anti-gliadin antibodies.

HLA DQW2, DR3/7

HLA associations

Correct answer

HLA DR/W2, DR/W3 and B8

Systemic lupus erythematosus

HLA B8/DR3

Dermatomyositis herpetiformis

HLA DR5/DR2

Kaposi’s sarcoma

HLA DR3

Chronic active hepatitis, Graves’ disease, myasthenia gravis, Addison’s disease and Sjögren’s syndrome, idiopathic membranous nephropathy, systemic lupus erythematosus

HLA DR2

Goodpasture syndrome, narcolepsy, multiple sclerosis, juvenile insulindependent diabetes mellitus

HLA DQW2,

Coeliac disease

DR3/7

HLA A3/B14

Idiopathic haemochromatosis

HLA A28

Schizophrenia

HLA B5

Behçet’s disease and arthritis of inflammatory bowel disease (IBD) (ulcerative colitis)*

HLA B27

Ankylosing spondylitis, psoriatic arthropathy**, Reiter’s disease, reactive arthritis***

HLA DR4

Rheumatoid arthritis

HLA DR5

Hashimoto’s disease, pernicious anaemia

HLA B35

Subacute thyroiditis

HLA DR2, 3, 4

Insulin-dependent diabetes mellitus

HLA A1, B8,

Linkage equilibrium in nephrotic syndrome, acquired immunodeficiency syndrome (AIDS)

DR3

*IBD arthritis:

10% of IBD sufferers get arthritis. Some get ankylosing spondylitis associated with HLA B27

**Psoriasis May:

show a weak HLA B27 link

***Reactive arthritis:

After Salmonella, Shigella, Yersinia enterocolitica, Camplyobacter and Reiter’s disease, i.e. causes of bloody diarrhoea

91-Theme: Hypersensitivity

Match the following types of hypersensitivity with the three clinical scenarios given:

A Type I – immediate and anaphylactic hypersensitivity

B Type II – cell-bound hypersensitivity

C Type III – immune complex hypersensitivity

D Type IV – delayed T-cell hypersensitivity

E Type V – stimulatory hypersensitivity

F Type VI – killer hypersensitivity

G Type VII

H Type VIII

I Type IX

J Type X

Scenario 1 A 3-year-old boy is currently undergoing stem cell bone marrow transplantation due to severe combined immunodeficiency. On examination, he is found to have an erythematous maculopapular blanching rash with marked erythema of the palms of the hands and soles of the feet. He is found to have associated abdominal pain, diarrhoea and jaundice. The boy is currently in his third week of treatment, and his recent phytohaemagglutinin (PHA) test confirms that his bone marrow has grafted. You are suspicious that he may be suffering from veno-occlusive disease with an associated rejection abnormality.

Which type of hypersensitivity is involved?

Type IV – delayed T-cell hypersensitivity

Correct answer

Scenario 2 A 12-year-old girl presents to the emergency department with a nonblanching purpuric rash over her lower limbs and buttocks. She is complaining of a mild abdominal pain and a virus-like illness. On examination, she is found to have red-purple purpura throughout her lower abdomen and posteriorly over her buttocks. She is also found to have swelling of the left ankle and right knee. Her investigations show her to have ++ protein and +++ blood in her urine; growth has,

however, proven negative. The girl’s blood pressure is currently normal, as are her other observations. You wonder whether this child is suffering from meningococcaemia or a vasculitis.

What type of hypersensitivity is involved?

Type III – immune complex hypersensitivity

Correct answer

Scenario 3 A child presents to the outpatient department with exophthalmia, biorbital proptosis, lid lag and loss of weight. Her thyroid function tests prove her to have a raised thyroxine (T4) level, and she is suspected of having hyperthyroidism.

Which type of hypersensitivity reaction is involved?

Type V – stimulatory hypersensitivity

Correct answer

There are six types of hypersensitivity:

Type 1 – This is an immediate and often anaphylactic reaction involving IgE, IgG4, mast cells and basophils. It involves a vasodilatory response, activation of eosinophils and leukotrienes, and the release of vasodilators such as histamine, serotonin and bradykinins. Histamine is a spasmogen, causing bronchial smooth muscle contraction. A wheal and flare is formed. The process is involved in:

Atopic disease

Asthma

Hay fever (pollen)

Eczema

Anaphylaxis

Food and drug intolerance

Bee and wasp stings.

For the purpose of exams, remember that sodium cromoglicate stabilises the mast cell membrane.

Type 2 – This is cell-bound hypersensitivity, which is antibody dependent and involves the cytotoxic cells. Here, circulating antibody (IgG and IgM) binds to cell–cell surface antigen receptors and activates complement, which causes cell

lysis/damage and macrophage opsonisation with neutrophil activation. This type of hypersensitivity is involved in:

Graves’ disease

Haemolytic anaemia

Myasthenia gravis

Idiopathic thrombocytopenic purpura (ITP)

Goodpasture syndrome

Hyperacute graft rejection

Reduction of ABO incompatibility

Role in cancer

Blockage of antibody.

Type 3 – This involves circulating immune complexes and is complement mediated. It is activated via IgG and IgA. There are three mechanisms for producing disease:

1. The combined effects of low fever and a weak antibody response

2. As a complication of autoimmune disease in which the continued production of antibody to self antigen forms complexes

3. The formation of immune complexes at the body surfaces, e.g. in the lungs.

Type 4 – This involves the cell-mediated immune system. It involves a delayed T-cell-mediated reaction. It is associated with:

Acute early rejection

Graft-versus-host disease (late rejection)

Rheumatoid arthritis

Contact dermatitis

Acute allergic alveolitis

The reaction in tuberculosis with the tuberculin skin test (72 hours) and granulomatosis (21–28 days)

The Heaf test response.

This delayed hypersensitivity is seen with:

Sarcoidosis

Malignant lymphomas such as Hodgkin’s disease

DiGeorge syndrome (absent or decreased T-cells)

Corticosteroid treatment

Leprosy (borderline)

Malnutrition

Wiskott–Aldrich syndrome

Crohn’s disease

Extrinsic allergic alveolitis

Schistosomiasis

Extreme old age – it decreases with age

It is not associated with the Arthus reaction.

Type 5 – This is stimulatory with IgG antibody, which results in:

Long-acting thyroid stimulation, which causes the prolonged stimulation of thyroid hormone

Graves’ diseases and hyperthyroidism.

Type 6 – This class involves killer cells, which lyse targets coated with antibody, e.g. tumours or helminths.

Note: Types 7–10 do not exist

92-Regarding tuberculin testing:

It

traditionally involves an injection into the extensor surface of the left forearm

The Heaf test should ideally be read between 48 and 72 hours

A

positive result occurs when the area of induration is > 5 mm

Is

negative if the Heaf grade is ‘1’

Induration > 15 mm requires further investigation and possible antituberculous chemotherapy

Tuberculin testing traditionally involves an injection into the flexor surface of the left forearm. The Heaf test is ideally read at 7 days (between 3 and 10 days) and the Mantoux test is read at 48–72 hours (but up to 96 hours). A positive result occurs when the area of induration is > 5 mm. N.B. the area of ‘flare’ is irrelevant.

The Heaf test is graded 0–4. Heaf grades 0–1 are negative and grades 2–4 are positive. Strongly positive reactions (i.e. Heaf grade 3–4 or induration > 15 mm) require further investigation and possible antituberculous chemotherapy. F F T T T

93-Theme: Immunisation

A No live vaccines

B No vaccines at all

C Normal immunisation schedule D

D Normal schedule with separate pertussis vaccine

E Normal schedule without BCG (Bacilel Camille–Guérin)

F Normal schedule and unconjugated pneumococcal vaccination

G Normal schedule without polio vaccine

H Normal schedule with substitution of single vaccines for MMR (measles,

mumps, rubella)

I Normal schedule without MMR

J Normal schedule without MMR or BCG

For each of the following children, choose the most appropriate immunisation policy from the above list. Each item may be used once, more than once or not at all.

Scenario 1 A child born in the UK with vertically acquired human immunodeficiency virus (HIV) infection.

Normal schedule without MMR or BCG

Correct answer

Some experts advise that measles vaccine can be given if the child has a CD4 count > 200. Mumps and rubella vaccines can be given singly.

Scenario 2 A child diagnosed on the autistic spectrum.

Normal immunisation schedule D

Correct answer

Autism is not a contraindication to any immunisation.

Scenario 3 A child who has sickle cell trait.

Normal immunisation schedule D

Correct answer

Children with sickle cell trait should receive the universal schedule. Those with sickle cell disease should receive the unconjugated vaccine at age 2-3 years, in addition to the conjugated vaccine as part of the universal schedule (see http://www.immunisation.nhs.uk/Immunisation_Schedule).

Note that BCG is NOT part of the UK’s universal schedule but may be offered in areas of high TB incidence.

94-With regard to Bacillus Calmette-Guérin (BCG):

High-risk infants should have a positive Heaf test before immunisation proceeds

It is safe in asymptomatic HIV-positive patients

It may be given at the same time as other live vaccines

It should be given after a positive tuberculin test

Offers some protection against leprosy

High-risk infants do not require skin testing before immunisation up to the age of 3 months. BCG should be given only after a negative tuberculin test. It can be given at the same time as other live vaccines; otherwise a gap of 3 weeks should be observed. There is a risk that a suboptimal response to both may occur if this gap is not observed. Live oral polio vaccine (OPV), which works by inducing gut immunity, is the exception and can be given at any time. HIV infection is an absolute contraindication to BCG vaccination. F F T F T

95-The following are notifiable diseases:

Acquired immune deficiency syndrome (AIDS)

Mumps

Tuberculosis (TB)

Rubella

Malaria

Mumps, TB, rubella and malaria are all notifiable diseases. F T T T T

96-IgA deficiency:

is the commonest form of primary immunodeficiency

usually presents as growth faltering

has an association with coeliac disease

is a contraindication to BCG (bacille Calmette–Guérin) immunisation

increases the risk of transfusion reactions

IgA deficiency is relatively common, affecting between 1 in 300 and 1 in 600 people. Most cases are subclinical in childhood, though they may present with atopy or recurrent infections of the respiratory tract or gastrointestinal system. There are known associations with autoimmune disorders, coeliac disease, Crohn’s disease, ulcerative colitis and malignancies in older patients. Many patients will develop antibodies against immunoglobulin A (IgA), and are at increased risk of anaphylaxis following transfusions as the donated blood will harbour IgA. T F T F T

97-Nitric oxide:

inhibits the aggregation of platelets

is the active moiety of glycerol trinitrate

production is inhibited by steroids

dilates the arterial circulation

increases pulmonary vascular resistance

Nitric oxide (NO) can be derived from endothelial cells, neuronal cells and macrophages. It inhibits the aggregation of white cells and platelets. Steroids inhibit macrophage nitric oxide synthases and reduce NO production. The main source of NO is the vascular endothelium, which is continuously dilated by basal synthesis of NO. Pulmonary vascular resistance is reduced by NO, and hence the gas may be used in patients who are difficult to ventilate. It is the active moiety of nitro-vasodilators, including glyceryl trinitrate. T T T T F

98-Lyme disease:

may present with a larva migrans rash

is best treated with cotrimoxazole in children

is caused by a spirochaete

causes cerebellar ataxia

causes Guillain–Barré syndrome

Lyme disease is caused by the spirochaete Borrelia burgdorferi, and is transmitted by ticks carried by wild deer and other animals. The characteristic rash is called erythema migrans, and evolves around a central bite up to 21 days after exposure. Most cases respond to a 3-week course of Amoxil or erythromycin. Complications include arthritis, cardiac involvement, and hepatitis. Neurological complications include cranial nerve palsies, Guillain–Barré syndrome, cerebellar ataxia and aseptic meningitis. Diagnosis is usually based on history and clinical findings, with supportive serology for Borrelia. F F T T T

99-Erythema nodosum is associated with:

sarcoidosis

Bartonella henselae infection

Crohn’s disease

ulcerative colitis

streptococcal infection

Erythema nodosum describes red or dark raised ovoid lesions of 1–3 cm on the shin, usually in girls over the age of 6 years. Systemic causes include sarcoidosis, Crohn’s disease, ulcerative colitis and vasculitis. Infective causes include Streptococcus infection, mycoplasma, tuberculosis, cat scratch disease (Bartonella henselae), Epstein–Barr virus, and histoplasmosis. Sulfonamides and the contraceptive pill can also cause this reaction. 4T

100-The following are absolute contraindications to measles–mumps–rubella ( MMR) vaccination:

autism

attention deficit disorder

HIV infection

previous mumps infection

hepatitis B infection

MMR is a live vaccine, and is contraindicated in patients with significant immunodeficiency, including those who have been on steroids during the previous 3 months, or those undergoing chemotherapy during the previous 6 months. The vaccine should be delayed if the child is febrile, or has another live vaccination in the previous 3 weeks. It should not be given during pregnancy. In the UK , it is recommended that children with HIV should not receive BCG, or vaccines for yellow fever or oral typhoid. However, they should be given routine inactivated vaccines and inactivated polio immunisation. MMR may be given as long as the child is not severely immunosuppressed at the time. Autism and attention deficit disorders are not contraindications to MMR , nor is there any evidence that MMR causes autism. 4 F

101-An 18-month-old male presents with recurrent pneumonia, ear infections and tonsillitis. The family history includes a previous male infant death at 2 years of age from pneumococcal meningitis. The parents are therefore very concerned and wish further investigations to be carried out.

After the results have returned, it is found that the child has absent or decreased levels of immunoglobulins A, G and M. He has reduced responses to blood group antibodies to immunisations and an increased percentage of E rosettes with red blood cells. His PHA and nitroblue tetrazolium (NBT) tests are normal. The ultimate disorder is X-linked agammaglobulinaemia.

Which of the following are appropriate treatments (more than one answer may be given)?

A course of benzylpenicillin for an acute pneumonia and tonsillitis

Azithromycin for 3 days every fortnight as a prophylactic antibiotic

Intravenous immunoglobulin

A booster vaccine to DPT, Hib and meningitis C

Bone marrow transplantation

X-linked agammaglobulinaemia is the most common immunoglobulin deficiency causing a deficiency in all the immunoglobulin classes. The gene is localised to the long arm of the X chromosome, with the abnormality being in the gene for the B- cell tyrosine kinase. It is more common in males. This disorder is associated with an increased risk of blood malignancies. It presents after 3–6 months of age when the level of IgG resulting from in utero placental transfer has decreased. The

child presents with recurrent bacterial infections in the first 2 years of life, namely lung and sinus infections. Causes of hypogammaglobulinaemia include:

1. Common variable immune deficiency

2. Hypogammaglobulinaemia with raised IgM (X linked)

3. Transient immune deficiency of infancy.

Prenatal diagnosis is possible. Investigations show a profound failure of Bcell development so plasma cells from the bone marrow are absent. There is an abnormal B-cell function and number so there are isohaemagglutinins or surface immunoglobulins. Investigations undertaken include those stated, including finding an increase in OKT3 (49–63% of cases). Neutrophil, lymphocyte, PHA, nitroblue tetrazolium (NBT), sweat test and T-cell function are all normal. The PHA test measures T-cell proliferation. The T-cell lymphocytes are identified by their ability to form rosettes with sheep red blood cells. T-cell proliferation gives the total percentage of lymphocytes; the number is increased if no B-cells are present. Monoclonal antibodies are now used to identify and characterize T-cells. Monoclonal antibodies against T3 receptors measure the total Tcell number, T4 receptors, the T helper cell population and T8 receptors in the T suppressor/cytotoxic (Ts/c) group. Treatment includes prophylactic antibiotics and intravenous immunoglobulins. Bone marrow transplantation is carried out if medical interventions fail. F T T T T

102-In Wiskott–Aldrich syndrome:

there are reduced numbers of large platelets

psoriasis is common

inheritance is X-linked

immune cells have defective motility

vasculitis is common

Wiskott–Aldrich syndrome (WAS) is X-linked. There is classically a triad of thromobocytopenia, eczema, and immunodeficiency. Platelets are small and have reduced volume. Associated features include vasculitis and autoimmunity, and a predisposition to lymphoproliferative diseases in later life. The underlying defect is due to loss of the WAS protein, which is important for cytoskeletal organisation and cell motility. The disease can be cured by bone marrow transplantation, and this should ideally be undertaken in children aged less than 5 years if a fully matched donor is available. F F T T T

103-In haematopoietic stem cell transplantation:

umbilical cord blood may be used

CD34 identifies stem cells

the donor and recipient must have identical major histocompatibility complex ( MHC) antigens

donor T cells cause graft versus host disease

growth retardation is a late complication

Haematopoietic stem cells ( HSC ) may be derived from bone marrow harvests or leukopheresis after a course of granulocyte-colony stimulating factor (GCSF). Umbilical cord blood collected at the time of delivery is a rich source of HSC and cord blood banks are being established. CD34 is a cell surface molecule that is routinely used to identify and select HSC. Patients may have a fully MHC-matched sibling donor, or there may be an unrelated matched volunteer donor. The risk of graft versus host disease (GVHD) is greatly increased if mismatched donors are used, although on occasion parental haplo-identical donors have to be used. GVHD is mediated by donor T cells, and T cells can be removed from the graft to reduce the risk. Late complications of HSCT include impaired immune reconstitution, growth retardation, autoimmunity and endocrine dysfunction. T T F T T

104-The polymerase chain reaction (PCR):

requires monoclonal antibodies

requires forward and reverse primers

requires restriction digestion enzymes

is used to quantify human immunodeficiency virus (HIV) load

may be used to amplify RNA

In polymerase chain reaction ( PCR ) reactions, two oligonucleotide primers (15–30 base pairs in size) are mixed with the target DNA , a mixture of deoxyribonucleoside triphosphates (dNTPs) and thermostable Taq polymerase. Primers are designated forward and reverse, depending on which strand of DNA they bind. There are three stages to each PCR cycle:

Heating to 95°C causes the DNA strands to separate (denaturation)

Cooling to 54°C allows the primers to anneal to each strand

Heating to 72°C results in incorporation of dNTPs.

The process results in exponential expansion of DNA after each cycle. Target RNA may be amplified by using reverse transcriptase (RT) to convert it to template DNA before use in a PCR reaction. HIV is an RNA virus that can be detected and quantified using an RT- PCR reaction. This is now routinely used to follow the efficacy of anti-retroviral treatment on HIV load. F T F T T

105-Kawasaki disease is associated with:

hydrops of the gallbladder

myocarditis

erythema of BCG vaccination site

desquamation of the perineum

cranial nerve palsy

The established criteria for the diagnosis of Kawasaki disease are 5 days of fever plus four of the following:

cervical lymphadenopathy

non suppurative conjunctivitis

exanthem

swelling or desquamation of the hands or feet

oropharyngeal inflammation.

Additional features include irritability, meningitis, iridocyclitis and arthritis. Dilatation or hydrops of the gallbladder is recognised. Erythema of a BCG immunisation site is a characteristic feature. Peripheral and cranial nerve palsies may occur. The development of coronary arteritis may lead to aneurysms and thrombosis, though all parts of the heart may be involved. 4T

106-Members of the innate immune system include:

T lymphocytes

antimicrobial peptides

insulin-like growth factors

complement C3

lectins

The innate or non-specific immune system is the first line of defence against pathogens. It
The innate or non-specific immune system is the first line of defence against pathogens. It

The innate or non-specific immune system is the first line of defence against pathogens. It has many components, including mechanical barriers (skin, mucous secretions) and soluble factors (complement, mannose-binding lectin) as well as neutrophils and macrophages. Anti-microbial peptides, such as β-defensins are proteins secreted by endothelial cells. Specific immunity is provided by T cells and

B cells, and results in the generation of immune memory, resulting in rapid

responses on subsequent challenge by a given pathogen. F T F T F

107-Apoptosis:

causes cellular shrinkage

is

an inflammatory process

is

mediated by caspases

is

induced by tumour necrosis factor (TNF)

is

induced by insulin

Apoptosis results in programmed cell death and is non-inflammatory. Apoptosis is needed for embryonic development in utero and tissue homeostasis in adult life. Apoptosis may be induced by soluble factors such as TNF-binding death receptors or the withdrawal of growth factors (e.g. insulin-like growth factors). During apoptosis cells shrink, chromatin condenses, with endonuclease activation and DNA cleavage. Caspases are important mediators of apoptotic signals within cells. Mutations in some genes or over-expression of others (e.g. bcl-2) may lead to a failure of apoptosis and the formation of tumourogenic cell populations. T F T T F

108-Disease-associated prions:

replicate in red blood cells

resist proteinases

may be detected by polymerase chain reaction (PCR)

are inherited with mitochondria

accumulate in the tonsils

According to the prion hypothesis, disease-causing prions are corrupted versions of naturally occurring prion proteins found on cell surfaces. Once corrupted they resist proteinase degradation, are heat stable, and are insensitive to ultraviolet light damage. Prions cause transmissible spongiform encephalopathies (TSEs) such as

BSE in cattle and Creutzfeldt–Jacob disease (CJD) in man. In 1996, new-variant CJD was first described and is thought to be caused by bovine prions entering the human food chain. Such prions are detectable in tonsil tissue. They do not encode genetic material and thus are not detectable by PCR. F T F F T

109-Following delivery, infants born to HIV-infected mothers should:

receive high-dose cotrimoxazole

commence triple therapy

avoid breast feeding

be immunised with BCG

receive high-dose immunoglobulin

In the UK , the current guidelines recommend treatment of infants of HIV-positive mothers with zidovudine (AZT) from birth. Nelfinavir is an alternative agent that may be used, in particular if the mother is known to have developed resistance to AZT. Triple therapy is not usually indicated at birth, but may be initiated if there were a rising viral load or a falling CD4 count. PCR for HIV is usually performed within 48 hours, and repeated at 6 weeks. If both are negative, therapy can be stopped and the baby followed up until antibody negative. Babies should not be breast fed, and should not receive BCG vaccination. Cotrimoxazole would usually be given from 6 weeks of age. There is no indication for immunoglobulin therapy. F F T F F

110-Recognised causes of thrombocytopenia are:

phenytoin

carbamazepine

heparin

protamine sulphate

tranexamic acid

Drug-induced thrombocytopenia may be as a result of direct toxicity on the megakaryocytes or as a result of immune-mediated platelet consumption. Common causes in children include phenytoin, carbamazepine, chloramphenicol, and co- trimoxazole. Heparin may induce immune-mediated platelet elimination 7–10

days after starting treatment. Protamine sulphate is used to reverse heparin anticoagulation effects and tranexamic acid is a pro-coagulant. T T T F F

111-Meningitis is suspected in a 3-week-old baby. Which of the following treatment combinations is MOST appropriate?

Vancomycin and cefotaximeof the following treatment combinations is MOST appropriate? Cefotaxime and aciclovir Ampicillin and cefotaxime Benzyl

Cefotaxime and aciclovircombinations is MOST appropriate? Vancomycin and cefotaxime Ampicillin and cefotaxime Benzyl penicillin and gentamicin

Ampicillin and cefotaximeVancomycin and cefotaxime Cefotaxime and aciclovir Benzyl penicillin and gentamicin Vancomycin and gentamicin

Benzyl penicillin and gentamicinCefotaxime and aciclovir Ampicillin and cefotaxime Vancomycin and gentamicin Under the age of 4 weeks, the

Vancomycin and gentamicinAmpicillin and cefotaxime Benzyl penicillin and gentamicin Under the age of 4 weeks, the common causes

Under the age of 4 weeks, the common causes of meningitis include: group B streptococci; Escherichia coli; Listeria monocytogenes. Other pathogens such as Haemophilus influenzae, Staphylococcus, and Klebsiella spp are less frequent. From the list of answers, the most appropriate presumptive therapy would be with cefotaxime and ampicillin. Cefotaxime provides broad spectrum cover against streptococci and Gram-negative organisms and the inclusion of ampicillin is essential to cover Listeria infections. 3

112-The MOST appropriate treatment for suspected scabies infestation in a 3- year-old child would be which of the following?

Benzyl benzoatein a 3- year-old child would be which of the following? Ketoconazole Permethrin Hydrocortisone Chlorhexidine The

Ketoconazolechild would be which of the following? Benzyl benzoate Permethrin Hydrocortisone Chlorhexidine The immune response

Permethrinbe which of the following? Benzyl benzoate Ketoconazole Hydrocortisone Chlorhexidine The immune response to the mite

Hydrocortisoneof the following? Benzyl benzoate Ketoconazole Permethrin Chlorhexidine The immune response to the mite Sarcoptes

ChlorhexidineBenzyl benzoate Ketoconazole Permethrin Hydrocortisone The immune response to the mite Sarcoptes scabiei humanis

The immune response to the mite Sarcoptes scabiei humanis causes itchy skin eruptions, often with an eczematous rash and excoriations. There may be burrows on the palms, soles and digits. The mite can survive for up to 36 hours away from the human host. All family members should be treated, and clothing and bed-linen should be washed. Treatment should be with permethrin (Lyclear) or malathion (Derbac) lotions. Older preparations, such as benzyl benzoate, should be avoided in children. Ketoconazole is an antifungal agent and is not indicated. There may be an indication for systemic antibiotics if lesions become infected. 3

113-Osteomyelitis of the femur is suspected in a 4-year-old child. From the list below, which is the MOST likely organism to be involved?

Group B streptococcusbelow, which is the MOST likely organism to be involved? Salmonella Mycoplasma pneumoniae Staphylococcus aureus

SalmonellaMOST likely organism to be involved? Group B streptococcus Mycoplasma pneumoniae Staphylococcus aureus Haemophilus

Mycoplasma pneumoniaeorganism to be involved? Group B streptococcus Salmonella Staphylococcus aureus Haemophilus influenzae B Osteomyelitis

Staphylococcus aureusGroup B streptococcus Salmonella Mycoplasma pneumoniae Haemophilus influenzae B Osteomyelitis 3–10 years is

Haemophilus influenzae BSalmonella Mycoplasma pneumoniae Staphylococcus aureus Osteomyelitis 3–10 years is more common in boys than

Osteomyelitis 3–10 years is more common in boys than in girls and there may be a history of trauma. The most commonly involved organism is Staphylococcus aureus and treatment should be intravenous flucloxacillin (plus fusidic acid). Other causes are Streptococcus pneumoniae or possibly Escherichia coli. In infants under 2 years of age alternative organisms include Group B streptococcus and Haemophilus influenzae type B. In patients with sickle cell disease, Salmonella and Gram-negative infections should be considered. Treatment may require surgical debridement and antibiotics should be given for 6 weeks. 4

114-Theme: Viral infections

A Herpes simplex virus

B Human herpes virus 6

C Influenza virus

D Adenovirus

E Epstein–Barr virus

F Cytomegalovirus

G Hepatitis A

H Hepatitis B

I Measles

J Mumps

K Rubella

Scenario 1 A 15-month-old infant presents to the emergency department with

a 3-day history of high fevers without any localising signs. She suffers a short

self-limiting febrile convulsion and is admitted for observation. The next day the fever lapses, but a red macular–papular rash develops over her trunk and abdomen.

Human herpes virus 6

Correct answer

HHV-6 is thought to infect 90% of infants by 2 years of age. The pattern of high fevers for 3 days without an obvious cause is characteristic. Febrile seizures are a relatively common mode of presentation. The roseola rash often appears as fever subsides, and may be macular or macular–papular and usually begins centrally, spreading later to the limbs and resolving in 48–72 hours. Although other viruses such as measles may cause a similar rash, the timing and fever pattern favour

HHV-6.

Scenario 2 A 10-year-old boy complains of headache and goes to bed early. The next morning he is found to be drowsy and confused. He is admitted to hospital where CT imaging reveals bilateral temporal lobe enhancement.

Herpes simplex virus

Correct answer

Though most of the viruses listed may cause meningoencephalitis, temporal lobe involvement is characteristic of herpes simplex virus infection. Cerebrospinal fluid (CSF) examination usually reveals a raised cell count, often with red cells present, and raised protein, but normal glucose level. The presence of the virus may be confirmed using PCR detection techniques. Treatment would be with high-dose intravenous aciclovir for 21 days.

Scenario 3 A 42-year-old man develops mild jaundice 1 month after a trip to Thailand. His 4-year-old son now presents with vomiting and diarrhoea. The child has been febrile and is thus receiving regular doses of paracetamol. His liver function tests are slightly deranged.

Hepatitis A

Correct answer

In early childhood hepatitis A usually causes self-limiting diarrhoea and vomiting. Mild hepatitis is common, though children rarely develop jaundice. There is often a nursery or home contact who has passed on the virus through the faecal–oral route. In this case it seems to have been the father. Though hepatitis B is prevalent in the far east, it is only transmitted by the blood borne route and does not cause diarrhoea.

115-A 4-year-old, fair-skinned red-haired boy presents to the emergency department with a long history of chronic viral illnesses associated with diarrhoea. He appears atopic with rhinorrhoea and eczema. The GP has given him four courses of antibiotics for presumed chronic otitis media. On examination, the boy is small, has a fever of 38.4°C and appears pale with small bruises over his shins. He has marked eczema over the extensor surfaces and behind the ears but no associated superinfection. He has conjunctivitis with red conjunctivae and thrush. Cardiovascular, respiratory and abdominal examination is unremarkable. The bloody diarrhoea grows Campylobacter.

Investigations reveal a white cell count of 5.5x10 9 cells/l, a haemoglobin of 10.4 g/dl and a platelet count of 30x10 9 cells/l, and he is lymphopenic. An immunoglobulin profile reveals a decreased level of IgM. The boy is commenced on oral erythromycin.

What is the most likely diagnosis?

Acute leukaemiaon oral erythromycin. What is the most likely diagnosis? Hyper-IgM syndrome Wiskott–Aldrich syndrome Ataxia

Hyper-IgM syndromeWhat is the most likely diagnosis? Acute leukaemia Wiskott–Aldrich syndrome Ataxia telangiectasia

Wiskott–Aldrich syndromemost likely diagnosis? Acute leukaemia Hyper-IgM syndrome Ataxia telangiectasia X-linked agammaglobulinaemia

Ataxia telangiectasialeukaemia Hyper-IgM syndrome Wiskott–Aldrich syndrome X-linked agammaglobulinaemia Infections found and type of

X-linked agammaglobulinaemiaWiskott–Aldrich syndrome Ataxia telangiectasia Infections found and type of associated immune deficiency

Infections found and type of associated immune deficiency

T-cell deficiency

B-cell deficiency

Neutrophil defect

Wiscott–Aldrich syndrome

Bruton’s disease

Chronic granulomatous disease

Ataxia telangiectasia

   

Primary immunodeficiencies are:

X-linked agammaglobulinaemia

Hyper-IgG syndrome

Severe combined immunodeficiency syndrome

Wiskott–Aldrich syndrome

Ataxia telangiectasia

DiGeorge syndrome

Hereditary angioneurotic oedema.

Antibody/B cells and Bacteria

T cells:

Viruses, especially herpes simplex, cytomegalovirus (CMV), Epstein–Barr and herpes zoster

Mycobacteria, especially live in macrophages Candida

Complement (rare):

Impaired C5–C9 complex of the complement cascade

Bacteria (meningococcal)

Lytic terminal complement pathway

Phagocytes:

Bacteria, especially in those immuno-compromised or undergoing cancer chemotherapy

Fungi

3

116-The MMR vaccine:

Is contraindicated in patients allergic to neomycin

Should not be given within 3 weeks of another live vaccine (except oral polio vaccine [Sabin])

Is safe in pregnancy

Commonly results in a rash with or without fever from day 5 to day 10, lasting approximately 2 days

Is contraindicated in patients who have received an injection of immunoglobulin within 3 months

The MMR vaccine is contraindicated in patients who are allergic to neomycin or kanamycin. In children who have had a previous anaphylactic reaction to egg, immunisation is not absolutely contraindicated and should be discussed with a local paediatrician or immunisation coordinator. The MMR vaccine should not be given within 3 weeks of another live vaccine, because this results in a suboptimal response. Likewise, it is contraindicated in patients who have received an injection of immunoglobulin within 3 months, because no response will be mounted in the presence of immunoglobulin that may contain antibodies to measles, mumps or

rubella. Pregnancy should be avoided for at least 1 month after immunisation, which may well result in a rash with or without fever from about day 5–10 lasting about 2 days. It is therefore sensible to provide advice on temperature control at the time of immunisation. T T F T T

117-Theme: Immunisations

A Acellular pertussis vaccine

B Conjugate pneumococcal vaccine

C Hepatitis A vaccine

D Hepatitis B vaccine

E Influenza vaccine

F Palivizumab (anti-RSV [respiratory syncytial virus] immunoglobulin)

G Ribavirin

H Salk polio vaccine

I Single measles vaccine

J Unconjugated pneumococcal vaccine

For the following situations, choose one vaccine from the list above that should be used instead of, or in addition to, the routine scheduled vaccines. Each item may be used once, more than once or not at all.

Scenario 1 An ex-premature baby is discharged in October with home oxygen. He has had the first three sets of the universal schedule (while an inpatient).

Palivizumab (anti-RSV [respiratory syncytial virus] immunoglobulin) answer

Correct

Ex-pre-term infants with chronic lung disease are at a much higher risk from respiratory infections. RSV is a major concern for babies with chronic lung disease, leading to high rates of hospital admission, PICU admission and even mortality. The evidence for passive immunisation against RSV shows that it will

not prevent infection or hospital admission with RSV bronchiolitis (in babies with chronic lung disease). However, it seems to reduce the severity of the illness, such that it reduces the need for PICU admission (NNT = 10 to prevent 1 PICU admission). There is some debate about whether this is cost-effective. Most neonatal ICUs will arrange the immunisation of babies with chronic lung disease.

Scenario 2 A 4-year-old whose sibling is receiving chemotherapy for AML.

Influenza vaccine

Correct answer

A child receiving chemotherapy for AML will be significantly immunosuppressed. If such a child has siblings, it is important that they are immunised against influenza, which can be devastating to an immunocompromised child. Previously a sibling would have received inactivated polio rather than live oral polio vaccine; however, since the change to the universal schedule (where all polio is inactivated) this is no longer a consideration.

Scenario 3 A 3-year-old infant has a splenectomy following a road traffic accident.

Unconjugated pneumococcal vaccine

Correct answer

This child may or may not have been part of the conjugated pneumococcal vaccine catch-up programme; however, as she is over 2 years old, it is important that she receive the unconjugated vaccine. At this age she will be able to make a good antibody response to the vaccine and the unconjugated vaccine protects against 30- 40 pneumococcal serotypes (compared with 7 serotypes for the conjugated vaccine).