Chapter 28 : Mechanisms of Pathogenesis in Tuberculosis

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In the 1890s, Robert Koch observed that a primary infection of guinea pigs with in the skin produced a nonhealing lesion and that reinoculation of the animals after several weeks produced only a firm, red nodule that necrosed and finally healed. These observations first suggested the existence of immunity to tuberculosis infection. While T-cell-derived lymphokines and the activated macrophage represent a necessary condition for protection, it is certainly not the whole story even in the mouse. A large proportion of human peripheral blood γδ T cells, even from PPD-negative donors, will proliferate in response to mycobacteria. Recent experiments involving infection of transgenic mice are providing new and interesting information on the role of some lymphokines and cytokines. In many chronic infections or inflammatory diseases, there is a permanent or transient switch from a Th1 pattern of response to Th2. Such a switch appears to occur, for example, in schistosomiasis and syphilis patients. The tissue-damaging responses are evoked by tuberculin, which is a very crude culture supernatant from old autolysing bacterial cultures precipitated by trichloroacetic acid or ammonium sulfate. Such supernatants contain fragments of essentially all the antigens of . The known capacity of mycobacterium containing adjuvants (Freund's complete adjuvant) to facilitate experimental induction of autoimmunity and evidence that mycobacterial disease can be accompanied by a sterile arthropathy have reawakened speculation that some autoimmune syndromes may be cryptic infections or may be triggered by past encounters with mycobacterium-like organisms.

Citation: Rook G, Bloom B. 1994. Mechanisms of Pathogenesis in Tuberculosis, p 485-502. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch28
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