A 45-year-old woman is found to have sarcoidosis with bilateral hilar lymphadenopathy. Biopsy shows tight, well-formed non-necrotizing granulomas with Langhans giant cells. Serum ACE is elevated. CD4:CD8 ratio in BAL is 5:1. Which immunological mechanism is central to sarcoid granuloma formation?

• A Type IV hypersensitivity (Th1 CD4+ lymphocytes secreting IFN-gamma activating macrophages into epithelioid cells) ✓
• B Type III hypersensitivity (immune complex deposition activating complement causing granuloma)
• C Type I hypersensitivity (IgE-mediated mast cell activation inducing eosinophil-rich granuloma)
• D Natural killer cell-mediated cytotoxicity against unrecognized antigen-presenting macrophages

Explanation

Sarcoidosis granulomas are driven by Type IV (cell-mediated, delayed-type) hypersensitivity. CD4+ Th1 lymphocytes accumulate and secrete IFN-gamma, which activates macrophages to transform into epithelioid cells and fuse into Langhans-type giant cells. IL-12 and IL-18 from antigen-presenting macrophages amplify Th1 polarization. The elevated CD4:CD8 ratio (>3.5:1) in BAL is diagnostic of sarcoidosis. ACE is produced by activated macrophages/epithelioid cells and reflects granuloma burden. There is no immune complex or IgE involvement in sarcoid.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.