Granulomatous inflammation

Pathophysiology

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• A distinct pattern of chronic inflammation characterized by aggregates of activated macrophages (epithelioid cells), often with a surrounding collar of lymphocytes. It’s a Type IV hypersensitivity reaction initiated by persistent, hard-to-eradicate antigens.

• Mechanism: Macrophages present antigens to CD4+ Th1 cells. Th1 cells then secrete IFN-γ, which activates macrophages, transforming them into epithelioid cells and fusing them to form multinucleated giant cells (e.g., Langhans giant cells). TNF-α is crucial for forming and maintaining granulomas.

  • This is the reason why anti-TNF therapy can promote sequestration of granulomas and cause disseminated disease.
  • Therefore, every individual considered for anti-TNF therapy has to be tested for latent TB beforehand.

• Purpose: To “wall off” a persistent offending agent that the immune system cannot easily eliminate, such as certain microbes or foreign bodies.

• Macrophages within the granuloma cause ↑ calcitriol activation due to ↑ 1α-hydroxylase activity → hypercalcemia