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Drosophila, the toll gene controls a powerful innate defense system against bacteria and fungi. Conserved through evolution, the mammalian innate immune system retains a family of homologous Toll-like receptors (TLRs) that are activated by microbial ligands to release cytokines that instruct the adaptive immune responses. Here we show that TLR2 activation leads to killing of intracellular Mycobacterium (M.) tuberculosis in both mouse and human macrophages. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric oxide-dependent killing of intracellular tubercle bacilli. In human monocytes and alveolar macrophages, bacterial lipoproteins similarly activated TLR2 to kill intracellular M. tuberculosis, however by an antimicrobial pathway that is nitric oxide independent. TLR2+CD14+CD68+ macrophages were detected in human lesions of tuberculous lymphadenitis within granulomas and surrounding foci of necrosis. These data provide evidence that mammalian TLRs have retained not only the structural features of Drosophila Toll that allow them to respond to microbial ligands, but also the ability directly to activate antimicrobial effector pathways at the site of infection.

We mention the major pathogenous characteristics of a tuberculosis infection. Immunity to tuberculosis and tuberculin allergy are connected with each other but are not identical reactions of the organism. We describe the well-known complications in primary infections, namely the primary focus and the formation of lymph nodes. The peripheral primary focus generally regresses after treatment. However, the hilar lymph nodes sometimes increase in size even after appropriate medication (autonomous activity of some lymph nodes). If x-ray films reveal segmental changes and if there is evidence of viral or mycoplasma infection, tuberculosis should be taken into consideration as a parallel disorder because these infections often pave the way for tuberculosis. In the stage of early generalisation miliaria may occur within 3 months of infection. In most cases miliaria escapes detection. Pleurisy involves tuberculosis bacteria entering the pleural cavity. One of the prerequisites of pleurisy is hyperergia of the pleura. If the patient has tuberculotic pleurisy it means that miliaria has already occurred and miliary tuberculosis need not be anticipated. We also mention secondary diffusion into the apex of the lung and its consequences.

Cells of MPS and lymphatic system in lymph nodes from eighteen patients with culture proven tuberculous lymphadenitis were examined by histological and immunohistochemical technics. Ten patients suffered from symptomatic HIV-infection and eight patients were immunocompetent individuals without HIV serology. Characteristic granulomas with or without caseation were observed in the eight immunocompetent and the four HIV-infected patients with less marked lymphopenia of CD4 positive peripheral blood lymphocytes. In lymph nodes from the other HIV-infected patients with more severe depression of CD4 positive peripheral blood lymphocyte count no epitheloid cell formation was present. Instead of these cells foamy macrophages were found. The phenotype of macrophages underwent progressive changes parallel to decreasing numbers of CD4 positive peripheral blood lymphocytes. Foamy macrophages in mycobacterium avium-intracellulare infection may represent an end-stage phenotype. While many macrophages and lymphocytes expressed IL-2 receptors in cases with typical granulomas there was no such CD25 expression in cases without any epitheloid cell formation. Our results suggest that T-cell activation is necessary for epitheloid granuloma formation in human tuberculosis and preliminary in situ data support the assumption that in vivo the HIV-infection provokes an excess production of cytokines which in turn causes an exhaustion of the immune system and finally AIDS.