Role of the Host Immune System in Protection against Tuberculosis
From DrugPedia: A Wikipedia for Drug discovery
M. tuberculosis bacilli are efficiently transmitted from person to person by aerosol. Only small numbers of bacilli are necessary to establish infection in the lung, because local innate immunity, mediated primarily by alveolar macrophages, fails to control growth of these slowly replicating bacilli. In most healthy adults, acquired immunity mediated by T cells controls but does not eradicate M. tuberculosis infection. One third of the world's population is thought to harbor persistent M. tuberculosis and ongoing immune surveillance by T cells is required to maintain control over them. Acquired immunity likely also protects against re-infection, which is important in parts of the world with high levels of M. tuberculosis transmission.
The interaction of T cells and infected macrophages is central to protective immunity to M. tuberculosis. CD4+ T cells have an essential role but are supported by other T cell subsets such as CD8+, gd TCR+ T cells (gd T cells), and CD1 restricted T cells. Antigens for these T cells are being defined, and their function in the immune response elucidated. Recent research has resulted in some insight into mechanisms used by macrophages to control M. tuberculosis. How T cells help them perform this task, however, remains poorly understood. TNF-alpha, IL-12 and IFN-gamma are central cytokines in regulation and effector phase of immune responses to M. tuberculosis.
Macrophages are not only primary effector cells for control of M. tuberculosis but also essential for processing and presentation of antigens to T cells. To survive (and thrive) in macrophages, M. tuberculosis has not only evolved mechanisms to live through the initial encounter with macrophage but also to block acquired immunity. Modulation of phagosomes, neutralization of macrophage effector molecules, inciting the secretion of inhibitory cytokines, and interference with processing of antigens for T cells, all represent strategies for bacterial survival. The relative importance of different T cell subsets and mechanisms employed by M. tuberculosis to interfere with macrophage and T cell function likely depends on the stage of infection. During primary infection an acute acquired immune response develops in the lung as innate immune mechanisms fail to control dividing bacilli. As replicating M. tuberculosis are controlled by activated T cells and macrophages, immune responses are down regulated, and the infection enters a chronic phase, in which memory T cells help macrophages in granulomas control persistent bacilli and provide surveillance against re-infection. Failure of acquired immunity during the acute and/or chronic phases allows M. tuberculosis infection to become clinically apparent, most commonly with pulmonary manifestations but in some with extra-pulmonary or disseminated disease. The balance of the interaction between T cells and infected macrophages determines the outcome of the host-pathogen interaction in M. tuberculosis infection. The ability to resist microbicidal functions and to modulate antigen processing and presentation allows M. tuberculosis to survive inside macrophages for many years. When host immunity fails, expectoration of reactivated bacilli allows the organism to seek a new host, perpetuating a cycle that allows M. tuberculosis to remain one of the most successful human pathogens.
