Takayasu arteritis (TA) predominantly affects the aorta and its major branches in young women. Histologically, the active phase shows granulomatous panarteritis with lymphoplasmacytic and giant cell infiltration of the media and adventitia. Which immunological mechanism drives the granulomatous destruction of the elastic arterial wall?

• A Molecular mimicry between Mycobacterium tuberculosis HSP65 and human aortic endothelial antigens activates cytotoxic CD8+ T-cells to kill endothelial cells, primarily driven by the innate immune system
• B Dendritic cells in the adventitial vasa vasorum present local aortic antigens (including HSP60) to autoreactive Th1 and Th17 CD4+ cells; Th1 cells (IFN-γ) activate macrophages to form giant cells and granulomata; Th17 cells (IL-17) recruit neutrophils; cytotoxic CD8+ cells further damage smooth muscle cells via perforin/granzyme, leading to medial destruction and subsequent fibrosis causing stenosis ✓
• C NK cells expressing perforin in the aortic wall directly lyse smooth muscle cells; IL-6 from NK cells recruits macrophages that form secondary granulomas
• D Immune complex deposition of anti-endothelial cell antibodies (AECA) in the arterial wall activates complement and recruits neutrophils, with secondary granuloma formation as a reaction to endothelial cell debris

Explanation

Takayasu arteritis pathogenesis involves a T-cell-driven granulomatous inflammation initiated in the adventitia. Antigen-presenting dendritic cells within the vasa vasorum (which supply the adventitia and outer media of large vessels) present aortic-derived peptides (including heat shock proteins) to autoreactive CD4+ T-helper cells. Th1 cells produce IFN-γ, activating macrophages to form Langhans-type giant cells and granulomata in the media; Th17 cells produce IL-17, recruiting neutrophils. Cytotoxic CD8+ T-cells expressing perforin and granzymes directly kill smooth muscle cells. The resulting medial destruction and fibrosis produce the characteristic stenotic lesions (and occasionally aneurysmal dilation). The disease is T-cell mediated (not immune complex mediated), though ANCA and AECA may be present as secondary phenomena.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.