Congenital Immunodeficiencies

Question 1

X-Linked SCID

Answer 1

Mechanism of Defect: 
Common GAMMA (y) receptor gene mutation that causes problem with the expression of IL2RY Receptor on the cell surface which causes no clonal expansion for T cells.

Result:
Normal B cell counts, but ZERO T-cell count

Question 2

Autosomal recessive SCID due to ADA deficiency/ Purine Nucleoside Phosphorylase Deficiency

Answer 2

ADA enzyme deficiency or Purine Nucleoside Phosphorylase deficiency leads to accumulation of TOXIC METABOLITES in the LYMPHOCYTES

Question 3

X-Linked Agammaglobulinemia (Bruton Syndrome)

Answer 3

Mechanism of Defect: there is a defect in the signaling pathway for the Bruton Tyrosine Kinase (BTK) which causes NO EXPRESSION OF IG-G on the cell

Result: B-cells stop prematurely at Pre-B cell stage and also cause an increase in Ig-M, Ig-A, Ig-E. Literally NO IG-G expressed AT ALL.

Question 4

Ig Heavy Chain Deficiencies

Answer 4

Chromosomal deletion of the gene responsible for the production of the heavy chain locus at 14q32 at G.

literally no Ig G present in the blood

Question 5

DiGeorge Syndrome

Answer 5

Decreased T cells due to the destruction of the thymus over time

-normal B cell count; decreased T cell amounts

Question 6

X-linked Hyper-IgM Syndrome

Answer 6

This hyper-mutation of IgM syndrome is the body trying to compensate for the dysfunction of the gene coding for the CD40L which causes major problems with membrane bound Ig Production. (IgA, IgE, IgG)

Question 7

Common Variable Immunodeficiency (CVID)

Answer 7

Hypogammaglobinemia–> no gamma heavy chain produced so the B cells can’t get through Pre-B cell phase

Result: Reduced or no production of selective isotypes or subtypes of immunoglobulins; susceptibility to bacterial infections or no clinical problems

Question 8

The Bare Lymphocyte Syndrome

Defective Class II MHC Expression

Answer 8

T-, B+, NK+

Mutation in the class II MHC expression and impaired CD4+ T Cell activation; defective cell-mediated immunity and T cell-dependent humoral immunity and T-cell dependent humoral immunity

Question 9

Defects in T Cell Receptor (TCR) complex expression or signaling

Answer 9

Rare mutations that are the result of CD3 or Zap70 gene mutations on gene

Results in lower than average T-cell counts (CD4/CD8 Cells)

Question 10

Defects in Th1 differentiation

Answer 10

Rare mutation that results from mutations encoding the receptors for IL-12

Decreased T-cell mediated Macrophage activity, susceptibility to infection

Question 11

Defects in Th17 differentiation

Answer 11

Decreased T cell mediated inflammatory responses; mucocutaneous cadidiasis, bacterial skin abscesses

Question 12

X-linked Lymphoproliferative Syndrome

Answer 12

SUPER-ANTIGEN CONCEPT–>
EBV Virus will bind to the Th and bind to the B cell creating a “glue” that will continuously activate each other causing constant proliferation

Question 13

Chronic Granulomatous Disease

Answer 13

Defective activation of reactive oxygen species by phagocytes creating a problem with the innate response to bacterial infections with oxidase activity

Question 14

Leukocyte Adhesion Deficiency

Answer 14

Mutations in gene encoding the B-chain of the integrin protein molecule for attachment

Neutrophilia in the blood ; the neutrophil can’t role into the site of infection via diapedesis

Question 15

Complement C3 Deficiency

Answer 15

Defect in complement cascade that causes complete problem with any complement activity

Question 16

Complement C2, C4 deficiency

Answer 16

If C2, C4 deficiency is present then there will be a failure to clear immune complexes and development of lupus like syndromes with vascular destruction (Type 3 Hypersensitivity)

Question 17

Chediak-Higashi Syndrome

Answer 17

Problem with granule formation and release in Macrophages and Natural Killer cells; mutation in gene encoding a lysosomal trafficking regulatory protein

Question 18

Recurrent Pyogenic Bacteria

Answer 18

Defect in innate immune responses to pyogenic bacteria

Question 19

Wiskott-Aldrich Syndrome

Answer 19

Defect in “WASP” protein which is necessary for the immune synapse for CTL to kill other cells via perforin and granzyme release

Sx: Eczema, Thrombocytopenia, immune deficiency