Primary Immunodeficiencies

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Selective IgA deficiency

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-The most common immunodeficiency
-Serum IgA <10 mg/dL
-15% also show IgG2 or IgG4 subclass deficiency
-May be asymptomatic or present with recurrent sinopulmonary infections and autoimmune, GI, and endocrine disorders

Front 2

What is the most common immunodeficiency?

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IgA deficiency

Front 3

What are some functions of IgA?

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-Neutralization
-Best IG for crossing epithelium
-Diffusion into extravascular sites

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X-linked agammaglobulinemia (X-LA)

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Bruton's agammaglobulinemia

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-affected male children have no B cells and little serum Ig
-Lymph nodes are small, tonsils are absent, and the serum has no IgA, IgM, or IgE
-Small amounts of IgG are found
-Responsible gene is found on the long arm of the X chromosome
-Rare disorder
-Expression begins at 4-6 months after maternal IgG is exhausted
-Victims are prone to recurrent bacterial infections

Front 5

Where are many of the genes responsible for immunodeficiencies found?

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Long arm of X chromosome

Front 6

Immunodeficiency with increased IgM

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-Rare disorder
-Increased serum IgM and deficient production of IgG and IgA
-May develope in first year of life or later
-Most common form is result of X linked recessive trait
-Genetic defect is in the CD40 ligand (CD154) on helper T cells, which must bind to CD40 on B cells in order to initiate antibody class switch from IgM to IgG or IgA
-Pts present with recurrent bacterial infections including otitis media, pneumonia, and septicemia.
-Some pts may have opportunistic viral or fungal infections due to a defect in cellular immunity (CD40 also on macrophages and dendritic cells)

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Common Variable Immunodeficiency (CVI)

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Adult onset aggammaglobulinemia

Hint 7

-onset at any age, but common in 2nd and 3rd decade
-clinical presentation is variable
-affects males and females equally
-Recurrent otitis medi or sinopulmonary infections occur along with persistent diarrhea
-Slow decline in total serum immunoglobulin due to a defect in B cell development; usually low serum levels of IgG and IgA

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DiGeorge Syndrome

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Congenital Thymic Aplasia

Hint 8

-Defect in thymus and parathyroids due to defect in development from the third and fourth pharyngeal pouches
-CATCH-22- Cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcemia resulting from chromosome 22q11 deletions
-T cell deficiency is variable depending on the extent the thymus gland is affects
-May have increased infections
-often presents as triad: Hypocalcemia, Diminished T cell function and Congenitival heart disease
-also associated with abnormal facies, growth retardation, cognitive defects, psychiatric, and behaviarol problems

Front 9

Wiskott-Aldrich Syndrom

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-Complete syndrome presents as eczema, recurrent pyogenic infection, and thrombocytopenia with unusally small platelets
-Diagnosed at birth by thrombocytopenia and family history
-X linked immunodeficiency that normally affects males
-May have elevated serum IgA and IgE but decrease IgM
-Defective T cell function and apprearance results results in recurrent infections

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What are some functions of IgM?

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-mainly activation of complement
-neutralization
-transport across epithelium

Front 11

What is the main function of IgE?

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-Sensitization of mast cells

Front 12

Severe Combined Immunodeficiency (SCID)

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-SCID infants develop recurrent serious infection early in life including abundant growth of Candida albican in the mouth and skin, pneumonia due to Pneumocystis jiroveci, prolonged diarrhea due to rotavirus or bacterial infection of the GI tract, fatal infections from live organism vaccines
-SCID usually fatal within first two years without bone marrow transplant
-Deficiencies in ADA or PNP in up to 50% of cases. Without these enzymes there is toxic accumulation of dATP and dGTP, especially in proliferating lymphocytes

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Chronic Granulomatous Disease

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-Patients get opportunistic infections which leads to compliations such as hepatosplenomegaly, lymphadenopathy, chronic draining lymph nodes, pneumonia, and chronic infected ulcerations and granuloma formation
-Onset 2 yrs
-X linked disorder most common but several genetic forms exist
-Defect in production of NADPH oxidase enzymes in phagocytic cells leads to a diminished respiratory burst which leads to a defect in intracellular killing of microbes

Front 14

Hereditary Angioedema (HAE)

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-characterized by recurrent attacks of edema of subcutaneous and submucosal tissues with typical attacks lasting 1-4 days usually without serious effect
-Edema of Upper Resp tract could obstruct patients breathing
-Edema in the intesines can lead to pain, cramps, and vomitting
-Rare
-Deficiency in complement control protein, C1 inhibitor, a serine protease inhibitor
-Deficiency in C1 inhibitor allows the complement cascade ot be easily activated and also allows for excess bradykinin production. C2-kinin and bradykinin acto on the post capillary venules to allow leakage of plasma and hence edema
-Treatment would include replacement of C1 inhibitor product

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Complement Component Deficiency

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-Pts missing proteins of the classical or alternative pathway may have serious infections and unexpectedly high incidence of autoimmune disease, especially SLE-like and glomerulonephritis (deficiency in C1, C2, or C4 proteins)
-Deficiencies of complement components can cause recurrent bacterial infections due to deficient complemtn opsonization and complement-assisted antibody production. Often deficiency of C3 protein
-Deficiencies of the membrane attack complex lead to a higher risk of Neisseria species infections