Granulomatous inflammation is characterized primarily by the accumulation of macrophages and activated T-lymphocytes, with increased production of key inflammatory mediators, Tumor necrosis factor alpha (TNF), Interferon gamma, Interleukin 2 (IL-2), IL-8, IL-10, IL-12, IL-18, IL-23 and transforming growth factor beta (TGF-β), indicative of a T helper cell-mediated immune response. Sarcoidosis has paradoxical effects on inflammatory processes; it is characterized by increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation, but immune response to antigen challenges such as tuberculin is suppressed. This paradoxic state of simultaneous hyper- and hypoactivity is suggestive of a state of anergy. The anergy may also be responsible for the increased risk of infections and cancer. The regulatory T-lymphocytes in the periphery of sarcoid granulomas appear to suppress IL-2 secretion, which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses. Schaumann bodies seen in sarcoidosis are calcium and protein inclusions inside of Langhans giant cells as part of a granuloma. Sarcoidosis is characterized by the formation of non-caseous epithelioid cell granulomas in various organs and tissues. While TNF is widely believed to play an important role in the formation of granulomas (this is further supported by the finding that in animal models of mycobacterial granuloma formation inhibition of either TNF or IFN-γ production inhibits granuloma formation), sarcoidosis can and does still develop in those being treated with TNF antagonists like etanercept. B cells also likely play a role in the pathophysiology of sarcoidosis. Serum levels of soluble human leukocyte antigen (HLA) class I antigens and angiotensin converting enzyme (ACE) are higher in people with sarcoidosis. Likewise the ratio of CD4/CD8 T cells in bronchoalveolar lavage is usually higher in people with pulmonary sarcoidosis (usually >3.5), although it can be normal or even abnormally low in some cases. Serum ACE levels have been found to usually correlate with total granuloma load. Cases of sarcoidosis have also been reported as part of the immune reconstitution syndrome of HIV, that is, when people receive treatment for HIV, their immune system rebounds and the result is that it starts to attack the antigens of opportunistic infections caught prior to said rebound and the resulting immune response starts to damage healthy tissue. Image:Sarcoidosis_(1)_lymph_node_biopsy.Sarcoidosis in a lymph node Image:Asteroid Body in Sarcoidosis.Asteroid body in sarcoidosis Image:Asteroid body intermed mag.Micrograph showing pulmonary sarcoidosis with granulomas with asteroid bodies, H&E stain
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medical cause of Hypercalcaemia
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