Flashcards in Primary Immunodeficiency Deck (32)
What are frequent viral and fungal infection indicative of?
T cell disorder
What are frequent bacterial infections indicative of?
B cell disorder
What are the tests for B cell function?
– Serum protein electropheresis
– Quantitation of specific Ig levels in blood
What on the CBC can indicate a T cell disorder?
X linked agammaglobulinemia
Mutation in a signaling tyrosine receptor that is mandatory for growth and development of B cells- specifically BLK-critical for the pre-BCR signal
What is the only pure B cell defect?
X linked agammaglobulinemia
What are the findings with X linked agammaglobulinemia?
- No Ig
- No B cells
How is X linked agammaglobulinemia treated?
Hyper IgM syndrome
Mutation of CD40L, known as CD154, on T cells
What is the inheritance pattern of Hyper IgM syndrome?
What are the findings with Hyper IgM syndrome and why?
• High IgM, low IgG and IgA because B cells not
prompted to isotype switch
• Switch not possible because of inability of T cells to be
activated and provide the switch cytokines
Selective IgA “deficiency”
No IgA is found - not a "true" deficiency though
What are the findings with IgA deficiency?
• IgG and IgM levels are normal
• IgA absent
What is the problem of transfusions with IgA "deficiency?"
Clinical problem is that ~10% of patients may have IgG anti-IgA antibodies. These may cause anaphylactic reactions during RBC transfusion or IVIg infusions
EBV X-linked agammaglobulinemia
• Underlying defect is a mutation in a signaling regulator of CD8 cells
• The mutation is activated by EBV infection of B cells
• If patient survives the EBV, B cell depletion by
cytotoxic T cells ensues and causes agammaglobulinemia
How does EBV X-linked agammaglobulinemia lead to death?
Ultimately die of global immune system dysfunction
because CD8 autoimmune attack on immune effector cells
Common Variable Immunodeficiency (CVID)
Fundamental defect is the inability of a B cell to differentiate to a plasma cell.
What are the findings of CVID?
• Decreased IgG, A and M levels are first abnormalities coming out from a normal childhood
• Progresses to overt T cell symptoms and then multiple autoimmune diseases, especially in the gut-PA, Celiac disease
What does CVID often culminate as?
Are there B cells present in CVID?
Yes! They just cannot differentiate into plasma cells
What is the treatment for CVID?
IVIG will work until T cell defects become prominent
There is no thymus present - deletion of 22q11.2
• Structural mutations in the 3rd and 4th branchial pouches (also called pharyngeal arches) - associated with Tetralogy of Fallot
What is often found with thyme aplasia?
Absent or deficient parathyroid glands and symptomatic
What are the findings with SCID?
Decreased or absent TRECS
Pathogenesis of Wiskott-Aldrich Syndrome
X linked recessive mutation of the WAS gene (cytoskeletal regulation)
What are the signs of Wiskott-Aldrich Syndrome?
• Moderate T cell deficiency
What are the signs of Ataxia-Telangiectasia?
• Oculocutaneous telangiectasia
• Recurrent infection of all kinds
• High rate of neoplasia-esp leukemia/lymphoma
• Extreme sensitivity to radiation-induced DNA damage and faulty repair
Bare lymphocyte syndrome
Defects in formation and transport of MHC I and II complexes to the cell membrane
Job (hyper-IgE) syndrome
• Autosomal dominant
• Eczema, recurrent T & B cell infections
• High IgE, impaired T cell function- especially Th17
Chediak Higashi Syndrome
• Recessive mutation
• Decreased intracellular protein transport
• Azurophilic granule formation affected in Ly and PMN
Chronic Granulomatous Disease
• X linked recessive, can be one of several mutations in NADPH respiratory burst system