14: Immunodeficiencies

Question 1

defect in humoral (B cell) immunity

Answer 1

infection by extracellular bac

Question 2

defect in CMI (T cell)

Answer 2

infection by viruses and intracellular bac, fungi

Question 3

Decreased serum Ig Levels, Normal skin test reaction

Answer 3

B cell deficiency

Question 4

Normal serum Ig levels, decreased skin test reaction

Answer 4

T cell deficiency

Question 5

germinal centers decreased or absent

Answer 5

B cell deficiency

Question 6

normal follicles, but decreased paracortical regions

Answer 6

T cell deficiency

Question 7

X linked agammaglobulinemia

Answer 7

• Absence of mature B cells due to mutation/deletion in B cell tyrosine kinase

Question 8

Common variable immunodeficiency

Answer 8

• mature B cells can’t differentiate into plasma cells resulting in decreased antibodies
• congenital or sporadic and linked with autoimmune diseases

Question 9

Selective IgA deficiency

Answer 9

• most common immunodeficiency
• Asymptomatic (IgM compensates for missing IgA)
• make all the antibodies except IgA
• B cells with surface IgA don’t differentiate into plasma cells

Question 10

X- linked Hyper IgM syndrome

Answer 10

• Overabundace of IgM antibody and lack of other antibody isotypes
• Inherited deficiency of CD40L on T cells means CD40 not engaged on B cells and isotype switching can’t occur

Question 11

Hyper IgM type 2 syndrome

Answer 11

• Overabundance of IgM antibody and lack of other antibody isotypes
• inherited mutation in the gene activation-induced cytidine deaminase which prevents isotype switching

Question 12

DiGeorge Syndrome “congenital thymic hypoplasia”

Answer 12

• Deficiency of T cells due to hypoplasia or agenesis of the thymus, no thymic shadow
• Defective maturation of T cells –> poor CMI against viruses and fungi
• Associated with maternal alcoholism and 22q11 deletions

Question 13

SCID (general)

Answer 13

• Failure of B and T cells to develop from bone marrow stem cells
• Spleen, lymph nodes, tonsils, and appendix not populated by B or T cells
• bone marrow transplantation or gene therapy is curative

Question 14

Autosomal recessive SCID

Answer 14

• deficiency of adensosine deaminase which catalyzes the deamination of adensoine and deoxyadenosine
• the accumulating adensosine and deoxyadenosine are toxic to lymphocytes

Question 15

RAG1/RAG2 deficiency SCID

Answer 15

• Failure of VDJ rearrangement in immunoglobulin and T cell receptor genes due to mutations in the RAG genes
• without recombination –> cell death

Question 16

X-linked SCID

Answer 16

• Mutation in gene for common gamma chain for cytokine receptors
• lymphocytes can’t develop properly without cytokine receptors

Question 17

Chronic Granulomatous Disease

Answer 17

• recurrent bacterial infections from early childhood (especially catalase+ bacteria)
• Defect in NADPH oxidase means neutrophils can’t produce superoxide anion during respiratory burst
• Increased levels of the cytokine G-CSF accounts for elevated neutrophil levels
• negative NBT dye reduction test

Question 18

Myeloperoxidase Deficiency (MPO)

Answer 18

• Decreased or absent myeloperoxidase ( coverts H2O2 to HOCl)
• NO increased susceptibility to infection due to compensatory mechanisms (may be decreased ability to fight fungal infections)

Question 19

Chediak Higashi Syndrome

Answer 19

• Recurrent bacterial infections, metallic silver hair, bleeding tendencies, impaired vision, hepatospenomegaly
• Neutrophils contain large cytoplasmic granules due to fusing of lysosomes –> reduces ability to kill microbes and impairs T cell and NK cell function

Question 20

Leukocyte Adhesion deficiency

Answer 20

• Defect in B chain of LFA1 and Mac1 adhesion molecules
• neutrophils cant adhere to endothelial cell wall for ecxtravasation
• recurrent bacterial and fungal infections of skin, lungs, blood, wound healing problems, EXTREME LEUKOCYTOSIS

Question 21

Wiskott-Aldrich Syndrome

Answer 21

• TRIAD: immunodeficiency, eczema, thrombocytopenia
• defective cytosolic protein that helps regulate the actin cytoskeletion of bone marrow-derived cells
• normal numbers of T and B cells which cannot traffic to sites of inflammation and b and T cells cannot interact properly
• Recurrent bacterial infection, predisposition to severe autoimmune diseases