Primary Immunodeficiency

Question 1

What are frequent viral and fungal infection indicative of?

Answer 1

T cell disorder

Question 2

What are frequent bacterial infections indicative of?

Answer 2

B cell disorder

Question 3

What are the tests for B cell function?

Answer 3

– Serum protein electropheresis

– Quantitation of specific Ig levels in blood

Question 4

What on the CBC can indicate a T cell disorder?

Answer 4

Lymphocytopenia

Question 5

X linked agammaglobulinemia

Answer 5

Mutation in a signaling tyrosine receptor that is mandatory for growth and development of B cells- specifically BLK-critical for the pre-BCR signal

Question 6

What is the only pure B cell defect?

Answer 6

X linked agammaglobulinemia

Question 7

What are the findings with X linked agammaglobulinemia?

Answer 7

• No Ig

- No B cells

Question 8

How is X linked agammaglobulinemia treated?

Answer 8

Pooled IVIG

Question 9

Hyper IgM syndrome

Answer 9

Mutation of CD40L, known as CD154, on T cells

Question 10

What is the inheritance pattern of Hyper IgM syndrome?

Answer 10

X-linked

Question 11

What are the findings with Hyper IgM syndrome and why?

Answer 11

• 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

Question 12

Selective IgA “deficiency”

Answer 12

No IgA is found - not a “true” deficiency though

Question 13

What are the findings with IgA deficiency?

Answer 13

• IgG and IgM levels are normal

* IgA absent

Question 14

What is the problem of transfusions with IgA “deficiency?”

Answer 14

Clinical problem is that ~10% of patients may have IgG anti-IgA antibodies. These may cause anaphylactic reactions during RBC transfusion or IVIg infusions

Question 15

EBV X-linked agammaglobulinemia

Answer 15

• 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

Question 16

How does EBV X-linked agammaglobulinemia lead to death?

Answer 16

Ultimately die of global immune system dysfunction

because CD8 autoimmune attack on immune effector cells

Question 17

Common Variable Immunodeficiency (CVID)

Answer 17

Fundamental defect is the inability of a B cell to differentiate to a plasma cell.


Question 18

What are the findings of CVID?

Answer 18

• 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

Question 19

What does CVID often culminate as?

Answer 19

Lymphoma

Question 20

Are there B cells present in CVID?

Answer 20

Yes! They just cannot differentiate into plasma cells

Question 21

What is the treatment for CVID?

Answer 21

IVIG will work until T cell defects become prominent

Question 22

Thymic aplasia

Answer 22

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

Question 23

What is often found with thyme aplasia?

Answer 23

Absent or deficient parathyroid glands and symptomatic

hypocalcemia

Question 24

What are the findings with SCID?

Answer 24

Decreased or absent TRECS

Question 25

Pathogenesis of Wiskott-Aldrich Syndrome

Answer 25

X linked recessive mutation of the WAS gene (cytoskeletal regulation)

Question 26

What are the signs of Wiskott-Aldrich Syndrome?

Answer 26

• Eczema
• Thrombocytopenia,
• Moderate T cell deficiency

Question 27

What are the signs of Ataxia-Telangiectasia?

Answer 27

• Oculocutaneous telangiectasia
• Recurrent infection of all kinds
• High rate of neoplasia-esp leukemia/lymphoma
• Extreme sensitivity to radiation-induced DNA damage and faulty repair

Question 28

Bare lymphocyte syndrome

Answer 28

Defects in formation and transport of MHC I and II complexes to the cell membrane

Question 29

Job (hyper-IgE) syndrome

Answer 29

• Autosomal dominant
• Eczema, recurrent T & B cell infections
• High IgE, impaired T cell function- especially Th17

Question 30

Chediak Higashi Syndrome

Answer 30

• Recessive mutation
• Decreased intracellular protein transport
• Azurophilic granule formation affected in Ly and PMN
• Albinism

Question 31

Chronic Granulomatous Disease

Answer 31

• X linked recessive, can be one of several mutations in NADPH respiratory burst system

Question 32

What are the complications of Chronic Granulomatous Disease?

Answer 32

• Neutrophils can phagocytize but can’t kill because cannot generate sufficient hydrogen peroxide
• Infections with catalase + organisms (Staph, fungi) are frequent - catalase counters the baseline H2O2