Primary Immunodeficiency (lecture)

Question 1

Deficiency in B cells will result in susceptibility to what type of pathogen?

Answer 1

Extracellular

Question 2

X-linked Agammaglobulinemia and X-linked Hyper-IgM Syndrome both result in deficiency of _-___

Answer 2

B-cells

Question 3

Male with extensive personal history of bacterial infections that began after 6 months of age and a family history of other males being similarly affected. Serology reveals a complete absence of any immunoglobulins. What is the gene that is responsible for his immunodeficiency?

Answer 3

This is XLA - the mutated gene is Bruton’s tyrosine kinase (btk)

Question 4

Male with extensive personal history of infections that began after 6 months of age and a family history of other males being similarly affected. Serology reveals an increase in IgM with absence of other Ig isotypes. Lymphnode histology reveals a lack of germinal centers. What is the gene that is responsible for his immunodeficiency?

Answer 4

This is X-linked Hyper-IgM Syndrome: It results from a mutation in the CD40 ligand gene (Xq26). The inability of B cells to link with CD40 ligand of T helper cells prevents Ig class switching from IgM to IgX.

Question 5

What cytokine is released from Th1 cells that results in activation of macrophages?

Answer 5

IFN-gamma

Question 6

2 y.o. male presents with recurrent severe viral, fungal, and bacterial infections. He is found to have B cells, but lacks T cells and NK cells. Family history reveals a brother that was born 3 years prior to him was similarly affected. What is the mutation responsible for this disease?

Answer 6

X-linked SCID is caused by a mutation of the common gamma chain of interleukin receptors. This results in an inability to stimulate NK and T cells.

Question 7

What does is CATCH-22 in DiGeorge Syndrome?

Answer 7

Cardiac abnormalities
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia/Hypoparathyroid
22 is the chromosome mutation (22q11)

Question 8

What is the inheritance pattern of DiGeorge?

Answer 8

Trick question - It is due to sporadic de novo mutations and is Autosomal Dominant

Question 9

What is the underlying issue in Leukocyte Adhesion Deficiency Type 1?

Answer 9

Inability of leukocytes to adhere to endothelial cells’ ICAM-1 receptor due to a mutation in leukocytes’ LFA-1.

Question 10

Young male with recurrent fungal and bacterial infections. Nitroblue tetrazolium dye reduction test of phagocytes shows no reaction. What is the underlying defect and findings on histology of the bowel?

Answer 10

Chronic Granulomatous Disease is due to a defect of superoxide anion production (esp . cytochrome b558/p91-phox). Histology will show microgranulomas, pigmented macrophages, and acute on chronic inflammation.