The macrophage to epitheliod conversion in Mycobacterium tuberculosis infection is mediated by:
Ref: Robbins Pathologic Basis of Disease, 8th edition, Pg: 183Explanation:T Cell-Mediated (Type IV) HypersensitivityThe cell-mediated type of hypersensitivity is initiated by antigen-activated (sensitized T lymphocytes, including CD4+ and CD8+ Tcells.Tubercle bacilli colonizing the lungs are persistent or nondegradable antigensThe perivascular infiltrate is dominated by macrophages over a period of 2 or 3 weeks.The activated macrophages often undergo a morphologic transformation into epithelium-like cells and are then referred to as epithelioid cells.A microscopic aggregation of epithelioid cells, usually surrounded by a collar of lymphocytes, is referred to as a granuloma.This pattern of inflammation, called granulomatous inflammation is typically associated with strong T-cell activation with cytokine production.M. tuberculosis enters macrophages by endocytosis mediated by several macrophage receptors: mannose receptors bind lipoarabino- mannan. a glvcolipid in the bacterial cell wall, and complement receptors bind opsonized mycobacteria.M. tuberculosis organisms replicate within the phagosome by blocking fusion of the phagosome and lysosomeAbout 3 weeks after infection, a T-helper 1 (TH1) response is mounted that activates macrophages to become bactericidal.Differentiation of TH1 cells depends on IL-12, which is produced by antigen-presenting cells that have encountered the mycobacteria.Mature TH1 cells, both in lymph nodes and in the lung, produce IFN-g.INF-g is the critical mediator that enables macrophages to contain the M. tuberculosis infection.IFN-g stimulates formation of the phagolysosome in infected macrophages, exposing the bacteria to an inhospitable acidic environment.Macrophages activated by IFN-y differentiate into the "epithelioid histiocytes" that characterize the granulomatous response, and may fuse to form giant cells.Activated macrophages also secrete TNF. which promotes recruitment of more monocytes.
TNF alpha
IFN-g
IL-4
TGF-Beia
Cells and Tissues of Immune System