A 27-year-old woman undergoes laparotomy for right lower quadrant pain and is found to have an inflamed terminal ileum. The involved segment of the intestine is removed, and the lesion observed on light microscopy is seen in the image.
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Which of the following cell types most likely mediated the formation of this patient's lesion?
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This patient has abdominal pain, ileal inflammation, and a noncaseating granuloma on biopsy, all of which are consistent with Crohn disease (CD). Noncaseating granulomas are seen only in a minority of patients with CD but, when present, are highly suggestive of the diagnosis. Microscopically, granulomas contain a large number of epithelioid macrophages that may fuse together to form multinucleated cells (Langhans giant cells), surrounded by a band of lymphocytes.
Granulomas are considered caseating or noncaseating:
Caseating: Central necrosis is present and has a granular, cheesy appearance. Caseating granulomas are typically seen in infectious etiologies (eg, tuberculosis, leprosy, syphilis, cat scratch disease) due to cell death (both macrophage and bacterial) and the release of cellular contents.
Noncaseating: No central necrosis is present. Noncaseating granulomas are typically seen in autoinflammatory conditions (eg, CD, sarcoidosis, common variable immune deficiency).
Granuloma formation is a product of chronic T-lymphocyte and macrophage activation in response to a difficult-to-eradicate antigen (eg, mycobacterium, self-antigens). Macrophages release tumor necrosis factor–alpha and other proinflammatory cytokines (eg, IL-6, IL-1, IL-12) that promote macrophage migration and Th1 cell differentiation. Th1 cells are thought to be important in granuloma organization; they produce IL-2 and interferon-gamma, which promote further T-cell response, activation of macrophages, and differentiation of macrophages into giant cells. Th17 cells are a proinflammatory subset of Th1 cells and contribute to the cell injury seen in CD.
(Choice A) B-lymphocytes differentiate into plasma cells and produce antibodies, thereby mediating the immune response to bacterial infection.
(Choice B) Eosinophils mediate defense reactions against certain parasites. They are also implicated in the pathogenesis of hypersensitivity reactions.
(Choice C) The main function of neutrophils is phagocytosis. They play an active role in nonspecific inflammatory processes.
(Choice D) Natural killer (NK) cells provide a nonspecific defense against virus-infected and tumor cells. They are not known to play a role in CD.
(Choice F) Th2 cells are involved in the pathogenesis of ulcerative colitis. They produce IL-5 and IL-13, which contribute to inflammation and damage of the intestinal mucosa.
Educational objective:
Granulomas are characterized by a large number of epithelioid macrophages that may fuse together to form multinucleated cells (Langhans giant cells) surrounded by a band of lymphocytes. Granuloma formation involves chronic Th1 and macrophage activation in response to a difficult-to-eradicate antigen.