Primary immunodeficiencies

Disease
Phagocyte cell function Chediak-Higashi Syndrome
Complement protein
B-cell development/ function Molecular Defects
T cell development/ function Granule structural defect
Combined B- & T- cell deficiencies

Symptoms
Phagocyte deficiency Recurrent infection with bacteria; chemotactic & degranulation
defects; absent NK activity; partial albinism
Chronic granulomatous disease
Chediak-hegashi syndrome
Leukocyte-adhesion deficiency Disease
Glucose-6-phosphate deficiency Leukocyte adhesion deficiency (LAD)
Myeloperoxidase deficiency
Molecular Defects
Phagocyte-Deficiency Diseases Deficiency of CD18 = βchain of β2 integrins; LFA-1, complement
receptor (CR3), CR4
Disease
Chronic Granulomatous Disease (CGD) Symptoms
Recurrent infection w/ extracellular bacterial pathogens because of
Molecular Defects defective opsonization, adhesion, mobilization & Chemotaxis
Deficiency of NADPH oxidase; failure to generate superoxide anion,
other O2 radicals
Disease
Symptoms Glucose-6-Phosphate dehydrogenase (G6PD) deficiency
Recurrent infections w/ catalase-positive bacteria & fungi
Molecular Defects
Deficiency of essential enzyme in hexose monophosphate shunt

Symptoms
Same as CGD
 Bruton X-linked hypogammaglobulinemia
First appear in childhood (>6 months)
Immunologic findings
Low immunoglobulin: all
Disease No circulating B cells
Myeloperoxidase deficiency Pre-B cells in the BM
(N) CMI
Molecular Defects Primary defect: a block in maturation of the B cell due to a
Granule enzyme deficiency deficiency of a tyrosine kinase

Symptoms Transient Hypogammaglobulinemia of infancy

Mild/ none Common variable (acquired) hypogammaglobulinemia
Immunoglobulin levels decrease with time
First appear in late teens to early 20s
Associated w/ autoimmunity in the patient or in the family
Complement Deficiencies A syndrome that is probably several different diseases
Low immunoglobulins à any class
C1sINH Hereditary Angioedema
B cells present in the peripheral blood
C2 Increased incidence of Connective
tissue d/o (SLE)
Selective Ig deficiency (dysgammaglobulinemia)
C1/C4//C2. Opsonization not efficient (LAD)
Several different diseases described
C3 Increased susceptibility to Selective IgA deficiency is the most common
pyogenic infection Repeated sinopulmonary infection, gastrointestinal disease
C5-C8. Recurrent Neisseria infection
Many w/ IgA deficiency have no symptoms
If both IgA and IgG2 subclass deficiencies, more likely to
B-cells deficiency
have infections
Recurrent pyogenic infection w/ extracellular pathogens
(-) Ig for opsonization & Complement activation
T-cell deficiencies
T cell intact
Px presents w/ viral/fungal infections
Bruton X-linked hypogammaglobulinemia
B-cell function: compromised by lack of T-cell help
Transient Hypogammaglobulinemia of infancy
Major defect: handling intracellular pathogens
Common variable (acquired) hypogammaglobulinemia
Px’s receiving immunosuppressive drugs for treatment of
Selective Ig deficiency (dysgammaglobulinemia) allograft may have similar problems with these organisms.
T-cell deficiencies Normal rxn : Deoxyadenosin➡️ Deoxyinosine
Di George syndrome (non-toxic)
Chronic mucocutaneous candidiasis ADA def: Deoxyadenosine ➡️ Deoxyadenosine Phosphate
(Toxic for T-cells & precursors)
Di George syndrome
Failure of development of third & fourth pharyngeal Severe Combined Immunodeficiency Disease (SCID)
pouches X-linked & Autosomal
Hypoplasmic thymus Early infancy (3 mths)
Hypoplastic parathyroid glands B & T cells: -/N not fxn N
Pneumocystic pneumonia ➡️ most common
Clinical features Def:
Class I & II molecules
Thymic apalsia T cell receptors
Recurrent viral & fungal infections Cytokine receptors
Hypoparathyroidism – hypocalcemic tetany Signal-transduction
Cardiac anomalies
Facial anomalies (fish mouth & flat face) Wiskott-Aldrich Syndrome (X-linked)
Triad:
Chronic mucocutaneous candidiasis Thrombocytopenia
Severe chronic skin & mucous membrane infections w/ the Eczema
fungal pathogen Candida albicans Immunodeficiency
Combined B & T cell deficiencies Inability to mount an IgM response to the capsular
Susceptible to bacterial, viral & fungal infections polysaccharide of bacteria, such as pneumococci
T cell def ➡️ predominates
Ataxia-Telangiectasia
Combined B & T cell deficiencies Develops 1-2 years of age
Adenosine deaminase (ADA) deficiency Sinopulmonary infections
Severe combined immunodeficiency disease (SCID) Autosomal recessive
Wiskott-Aldrich Syndrome Ataxia: uncoordinated muscle movements
Ataxia-telangiectasia Telangiectasia: dilation of small vessels; seen in sclera of eye
Immunodeficiency
Adenosine deaminase (ADA) def Selective IgA deficiency
1st human disease successfully treated w/ gene therapy Cell-mediated defects- variable
Other immunoglobulin- varaible
In summary:

Immune deficiency Predominating

opportunist

B-cells Pyogenic bacteria

T-cells Viruses, Fungi,

Mycobacteria

C3 Pyogenic bacteria

C5-8 Neisseria