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Pathology · Immunopathology: granuloma and TNF
Sample itemA 48-year-old woman with rheumatoid arthritis begins infliximab. Six months later she develops fever, weight loss and miliary shadows on chest radiograph, and biopsy shows poorly formed granulomas with many bacilli. What explains the reactivation of tuberculosis?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
B. Neutralised TNF-alpha, which is needed to maintain granuloma integrity and macrophage activation
Granulomas arise when CD4+ Th1 cells secrete IFN-gamma that activates macrophages, and TNF-alpha made by macrophages helps recruit cells and maintain the granuloma wall. TNF blockers such as infliximab disrupt granulomas and cause latent tuberculosis to reactivate, so screening for latent TB is required before starting them.
Option by option
A. Depletion of B cells with loss of protective antibody
B-cell depletion describes rituximab, and antibody is not the main defence against intracellular mycobacteria.
B. Neutralised TNF-alpha, which is needed to maintain granuloma integrity and macrophage activation (correct)
Correct. TNF blockade breaks down the structure that contains the bacilli.
C. Inhibition of complement activation by the drug
Infliximab acts on TNF and not on complement, which is not the main control of mycobacteria.
D. Complete loss of IFN-gamma gene expression
The drug neutralises TNF; it does not delete IFN-gamma genes.
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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