Humans generally have a rather high innate immunity to development of disease. This was tragically illustrated in the Lübeck disaster of 1926 where infants were administered M. tuberculosis instead of an intended vaccine strain. Despite the large dose, only 76 of249 died and most of the others developed only minor lesions. Approximately 10% of im-munocompetent persons infected with M. tuberculosis will develop active disease any time in their life. There is epidemiologic and historic evidence for differences in the im-munity in certain population groups and between identical and nonidentical twins.
DTH to tuberculoprotein and CMI to M. tuberculosis develop 2 to 6 weeks after primary infection. The subsequent course of the infection depends on the balance between these two defensive mechanisms. DTH, through the mediation of natural killer cells, destroys the inac-tivated macrophages as well as the surrounding tissues, releasing still viable mycobacteria into an area of necrosis unsuitable for bacterial multiplication. CMI develops when compe-tent T lymphocytes recognize mycobacterial antigen complexes on the surface of M. tubercu-losis – containing macrophages. In the presence of macrophage-produced interleukin-1, theactivated lymphocytes respond to the presented antigens with the elaboration of several cytokines. Some of these proteins attract circulating monocytes. Others, including interferon-and possibly tumor necrosis factor- , activate local tissue macrophages and the recruited monocytes to enhanced destruction of ingested mycobacteria, resulting in a slowing or discontinuation of intracellular bacterial growth. Nitrous oxide or other reactive nitrogen in-termediates probably mediate the destruction of the mycobacteria. Another cytokine, inter-leukin-2, induces clonal expansion of the activated lymphocytes, thus amplifying the host’s immunologic response. Still others stimulate accumulation of fibroblasts and deposition of collagen, which help wall off the area of infection and prevent further dissemination.
Acquired immunity is cell mediated but incomplete. Both helper – inducer (CD4+) and cytotoxic (CD8+) T lymphocytes are involved. Two to three weeks after infection, macrophages are activated at the site of infection by a network of pro- and anti-inflammatory cytokines and chemokines from antigen-stimulated CD4+ T lymphocytes, macrophages, and dendritic cells. This interaction between M. tuberculosis and the host is what eventually limits its multiplication and spread. Cytotoxic T cells release bacilli from inac-tivated phagocytic cells and allow them to be ingested and handled by the activated macrophages. The concomitant DTH to tuberculoprotein plays an important part in im-munity to reinfection by mobilizing immune cells and macrophages to the site of deposi-tion of tubercle bacilli. In the past, it was believed that reinfection from external sources was extremely rare, but it is now clear that loss of hypersensitivity and CMI can occur over time and that reinfection can develop into clinical tuberculosis.
The role of DTH in immunity of established tuberculosis is complex, because high degrees of sensitivity can precipitate caseous necrosis and lead to spread of the disease. The importance of CMI and hypersensitivity in modulating the course of tuberculosis is, perhaps, most dramatically illustrated in patients with AIDS. Those with minimal impair-ment of cellular immune responses develop typical tubercles containing relatively few bacilli. Those with advanced impairment demonstrate abundant acid-fast bacilli without epithelioid cell accumulation or associated tissue necrosis.
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