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Microbiology · Immunology: IL-12 and interferon-gamma axis
Sample itemA 7-year-old boy develops disseminated infection after BCG vaccination, followed by recurrent non-tuberculous mycobacterial infection and Salmonella bacteraemia. HIV is negative, immunoglobulins and lymphocyte counts are normal, and the dihydrorhodamine oxidation test is normal. Which defect is most likely?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
A. Defect in the IL-12 and interferon-gamma pathway of Th1 immunity
Intracellular pathogens are controlled when IL-12 from macrophages drives Th1 cells to produce interferon-gamma, which activates macrophage killing. Mutations in IL-12Rbeta1, IL-12p40 or the interferon-gamma receptor cause Mendelian susceptibility to mycobacterial disease, with severe BCG, atypical mycobacteria and Salmonella infection. A normal oxidative burst test argues against chronic granulomatous disease.
Option by option
A. Defect in the IL-12 and interferon-gamma pathway of Th1 immunity (correct)
Impaired IL-12 and interferon-gamma signalling selectively cripples control of mycobacteria and Salmonella.
B. Defect in the integrin CD18 chain
CD18 deficiency causes leukocyte adhesion deficiency with delayed umbilical cord separation and neutrophilia.
C. Defect in Bruton tyrosine kinase
BTK deficiency causes agammaglobulinaemia, in which immunoglobulins would be low.
D. Defect in phagocyte NADPH oxidase
NADPH oxidase deficiency causes chronic granulomatous disease, which would give an abnormal dihydrorhodamine test.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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