Beruflich Dokumente
Kultur Dokumente
6th November
1.
What is an allergen?
Any substance which causes an allergic reaction. Allergens are environmental antigens which provoke a type 1
hypersensitivity reaction. Atopic individuals have a genetic predisposition to development of type 1 hypersensitivity. In
their case harmless antigens stimulate an Ig-E response inappropriately which leads to the allergic reaction.
2.
What is histamine?
Histamine (C5H9N3) is released from mast cells and basophils in an allergic reaction. It is made by removing a CO2
molecule from the amino acid histidine with the enzyme L-histidine decarboxylase. It is then inactivated by other
enzymes and stored in granules in mast and basophil cells.
Histamine binds to histamine receptors of which there are 4 types H1- H4, all of which are members of the G proteincoupled family of receptors. H1 receptors are found on most cells but predominantly on smooth muscle, the CNS and
vascular endothelial cells. Binding to H1 brings around most of the effects associated with histamine release including
contraction of intestinal and bronchial smooth muscle, increased venule permeability and increased mucus secretion. H 2
receptors are bound to adenylate cyclise via another protein and receptor activation stimulates cAMP production and
2+
increases the concentration of Ca Binding of histamine to H2 receptors increases vasopermeability and vasodilatation,
stimulates exocrine glands and increases the production of stomach acid. When histamine binds to H 2 receptors a
negative feedback loop is established and degranulation is suppressed. H3 receptors are found in the nervous system
(mainly the CNS). They act as receptors for histamine when it is functioning as a neurotransmitter for histaminergic
neurons. Activation of the receptor leads to inhibition of histamine and cAMP formation, neurotransmitter release and
induction of sleepiness. H4 receptors are highly expressed in bone marrow and white blood cells and regulates
neutrophil release from bone marrow. They are also found in the colon, liver, lung, small intestine, spleen, testes,
thymus, tonsils, and trachea. They mediate chemotaxic signaling from mast cells by decreasing cAMP levels. Inhibition of
H4 receptors can be used to treat allergies and atopic asthma as if the mast cells cant release their cytokines,
lymphocytes dont flock to the area so no inflammatory response is brought about.
Itching caused by histamine is thought to be due to H1 and H4 receptors being stimulated by histamine. H3 antagonists
have the reverse effect and relieve the itching sensation. When histamine and H1 bind, phospholipase C is activated
which increases the amount of Ca2+ in the unmyelinated sensory neurons which causes an action potential to the brain.
Activation of H4 receptors also increases Ca2+ levels in the cell. As it exists in sensory neurons an action potential is
triggered. Itch receptors are only found in the epidermis and dermis, mostly in the stratum basale.
3.
What is antihistamine?
Antihistamines are also called H1 antagonists they counteract the physiological effects of histamine. This is achieved by
competing for the receptors. They suppress the vasodilatation, itching and scratching caused by histamine release.
4.
5.
What is Ig-E?
An antibody produced in the lungs, skin and mucosa. Normally makes up 0.05% of serum antibody levels but it is still
capable of providing a very strong response. IgE binds very tightly to Fc receptors on basophils, mast cells and
neutrophils before interacting with antigen. As a result of its binding to basophils and mast cells, IgE is involved in
allergic reactions. Binding of the allergen to the IgE on the cells results in the release of histamine and heparin granules.
IgE levels also rise in parasitic diseases, measuring IgE levels is helpful in diagnosing parasitic infections. Eosinophils have
Fc receptors for IgE and binding of eosinophils to IgE-coated helminths results in killing of the parasite.
Atopic individuals have up to 10x more IgE in their blood which leads to more degranulation of histamine, even when
there is only a small amount of antigen present. Mast cells are primed for histamine release from their long term IgE Fc
interaction.
Somatic rearrangement of antibodies (V (D) J rearrangement) involves the rearrangement of DNA in somatic cells so the
recombined genes are not passes between generations. Therefore each individual has their own unique Ig repertoire.
The process is regulated by enzymes. Exons are rearranged by cleaving the DNA before transcription which leads to a
variety of light and heavy chains being formed.
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Somatic hypermutations occur commonly (1x10 mutations per base pair per generation). Individual nucleotides are
substituted altering the specificity of the antibody. It is more common in IgG and IgA than in IgM antibodies and affects
the heavy chain more than the light chain.
Type
Description
IgA
Found in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents
colonization by pathogens. Also found in saliva, tears, and breast milk.
IgD
Functions mainly as an antigen receptor on B cells that have not been exposed to antigens. It has
been shown to activate basophils and mast cells to produce antimicrobial factors.
IgE
Binds to allergens and triggers histamine release from mast cells and basophils, and is involved in
allergy. Also protects against parasitic worms.
IgG
In its four forms, provides the majority of antibody-based immunity against invading pathogens. The
only antibody capable of crossing the placenta to give passive immunity to fetus.
IgM
Expressed on the surface of B cells and in a secreted form with very high avidity. Eliminates
pathogens in the early stages of B cell mediated (humoral) immunity before there is sufficient IgG.
6.
7.
8.
What is eczema?
A form of dermatitis/ inflammation of the epidermis. Symptoms include dry, itchy, red sin which is often
thickened in affected areas from scarring - a protective response caused by continual scratching. Lumps and
blisters may be present form separation of dermis and epidermis. Infections often occur as bacteria enter
through weakened epithelium (stratum corneum often completely removed by scratching -> reduced physical
barrier to external environment). There are several types of eczema; atopic (allergic), irritant, contact, discoid
(random regions on otherwise normal skin) and seborrhoeic (nappy areas, scalp, folds of nose and mouth often caused by yeast). Crusty skin is caused by oozing of tissue fluid containing proteins. When the liquid
evaporates the proteins remain, usually occurs in conjunction with an infection (Staph. aureus -> yellow crust).
th
Prevalence of eczema has rapidly increased in the 20 century. 75% of children get eczema at some point,
10% still have it at adulthood.
Atopic, or endogenous, eczema has a genetic influence. Skin reacts abnormally
easily to allergens which causes a flaky, red appearance. Flexures are commonly
affected skin hardens on flexures making the joint harder to move which can cause
deep cracks and fissures. Sufferers are usually diagnosed before the age of 1 (50%)
and usually have serum IgE levels up to 10 times higher than normal -> easy to
trigger major immune response.
Treatments: avoid the irritant (to avoid an inflammatory response hard to implement), moisturisers (frequent
application even when not flared up), steroids (reduce inflammation), antibiotics (treat any secondary
st
infections), 1 generation antihistamines (sedative effect to help sleep and reduce the itch).
9.
Autoimmune disease incidence has gone up (MS, type 1 diabetes, rheumatoid arthritis, atherosclerosis,
alzeimhers, Parkinsons disease, certain cancers)
Infection
1.
2.
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4.
Entry to body skin, mucosa, mucus secretions, gut bacteria, stomach acid normal barriers
Replication and spreading of bacteria within body
Disease symptoms
Exit from the body and infection of other individuals
Innate
Viral infections within cells lead to interferon production acts on cells for protection and antiviral response
Natural killer cells recognise injected cells and kill them without being damaged in the process. Stops viral replication
Specific
Lymphocytes migrate to lymph nodes
Spleen removes old red blood cells
Antigens are usually proteins but can also be carbohydrates, lipids or DNA
Antibodies recognise part of the antigen
CD8 T cells kill virally infected cells
MHC is a protein complex on the surface of cells which binds to antigen fragments. Reacts with CD8 cells
Memory B cells provide a bigger, faster response to secondary infections
Biological barriers
Skin functions:
Skin epidermis is acidic and dry inhospitable to bacteria. Resident flora includes Staphylococcus (epidermidis and aureus) and
streptococci.
Skin dermis contains fibroblasts, lymphocytes, adipocytes, mast cells, macrophages, nerves, lymphatics, connective tissue,
Pacinian corpuscles, Merkel cells, Meisseners corpuscles, deep and superficial vascular plexuses.