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Paper II — 2013 September (Supplementary) (2010 Scheme) — Q10

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Paper II
2013 September (Supplementary) (2010 Scheme) · 40 marks · 120 min

Question

Gamma interferon.

Q102 marksShort Notes

Answer

Interferon-gamma (IFN-γ, “immune/type II interferon”) is a cytokine produced mainly by activated T lymphocytes (Th1 cells and CD8+ cytotoxic T cells) and NK cells, distinct from the type I interferons (IFN-α/β), which are produced by virtually all cell types in direct response to viral infection.

Key functions:

  • Macrophage activation — the single most important function of IFN-γ; markedly enhances the microbicidal capacity of macrophages (increased phagocytosis, respiratory burst, nitric oxide production), making it central to defence against intracellular pathogens, particularly Mycobacterium tuberculosis.
  • Upregulation of MHC expression — increases expression of both MHC class I and (especially) MHC class II molecules on antigen-presenting cells, enhancing antigen presentation and T-cell activation.
  • Promotion of Th1 differentiation — drives naive CD4+ T cells toward the Th1 phenotype, reinforcing cell-mediated immune responses (a positive feedback loop, since Th1 cells are themselves a major source of IFN-γ).
  • Antiviral activity — has some direct antiviral effect, though weaker/less broad than type I interferons.
  • Granuloma formation/maintenance — essential for forming and maintaining the caseating granulomas that contain M. tuberculosis infection; this is the mechanistic basis for the recognized risk of tuberculosis reactivation in patients treated with anti-TNF or other agents that disrupt this pathway.

Clinical/laboratory relevance: the basis of Interferon-Gamma Release Assays (IGRAs), which measure IFN-γ released by a patient’s sensitized T cells on exposure to M. tuberculosis-specific antigens in vitro — used for diagnosing latent TB infection, with better specificity than the tuberculin skin test since IGRAs are unaffected by prior BCG vaccination. Deficiency of the IFN-γ/IL-12 signalling axis (e.g., in certain rare inherited immunodeficiencies) predisposes to severe, disseminated mycobacterial infections (including with normally weakly pathogenic environmental/BCG strains).

  1. 1General Properties of Viruses and Virus Host Interaction

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