Immunology of Tuberculosis

Abstract

The resurgence of tuberculosis worldwide has intensified research efforts directed at examining the host defense and pathogenic mechanisms operative in Mycobacterium tuberculosis infection. This review summarizes our current understanding of the host immune response, with emphasis on the roles of macrophages, T cells, and the cytokine/chemokine network in engendering protective immunity. Specifically, we summarize studies addressing the ability of the organism to survive within macrophages by controlling phagolysosome fusion. The recent studies on Toll-like receptors and the impact on the innate response to M. tuberculosis are discussed. We also focus on the induction, specificity, and effector functions of CD4(+) and CD8(+) T cells, and the roles of cytokines and chemokines in the induction and effector functions of the immune response. Presentation of mycobacterial antigens by MHC class I, class II, and CD1 as well as the implications of these molecules sampling various compartments of the cell for presentation to T cells are discussed. Increased attention to this disease and the integration of animal models and human studies have afforded us a greater understanding of tuberculosis and the steps necessary to combat this infection. The pace of this research must be maintained if we are to realize an effective vaccine in the next decades.

Protective effect of DNA vaccine during chemotherapy on reactivation and reinfection of Mycobacterium tuberculosis

“…Tuberculosis (TB) holds the dubious honor of being the leading single-agent infectious disease killer in the world 1,2 and the situation is worsened by the increasing incidence of both multidrug resistant (MDR) stains and combination with AIDS. 1,3 After Mycobacterium tuberculosis infection, active disease arises in about 5% of exposed individuals and most of the others will develop a latent infection in which the tubercle bacilli can persist in vivo without causing any clinical symptoms. However, active disease may also develop decades later either as a relapse of the initial infection or because of a secondary infection.…”

Tuning inflammation in tuberculosis: the role of decoy receptors

“…This process is dependent on the activation of mycobacteria-reactive T lymphocytes [30], particularly IFNg-secreting CD4 and CD8 T cells [31]. Granuloma formation, however, is a complex process that requires not only the activation of lymphocytes, but also their recruitment with monocytes to the site of the infection, migration into the tissues, and juxtaposition around mycobacteria-infected macrophages [30].…”

“…Granuloma formation, however, is a complex process that requires not only the activation of lymphocytes, but also their recruitment with monocytes to the site of the infection, migration into the tissues, and juxtaposition around mycobacteria-infected macrophages [30]. This colocalization facilitates the activation of bactericidal mechanisms in infected macrophages by T cellderived cytokines [30]. Some mycobacteria, however, survive within macrophages, and persistent antigenic stimulation perpetuates the process, leading to chronic granuloma formation characterized by dense accumulations of infected macrophages, epithelioid cells, and T lymphocytes [30].…”

“…This colocalization facilitates the activation of bactericidal mechanisms in infected macrophages by T cellderived cytokines [30]. Some mycobacteria, however, survive within macrophages, and persistent antigenic stimulation perpetuates the process, leading to chronic granuloma formation characterized by dense accumulations of infected macrophages, epithelioid cells, and T lymphocytes [30]. These granulomas contain the mycobacterial infection and prevent dissemination to other organs, but they are also responsible for lung immunopathology, as the granulomas displace and destroy parenchymal tissue [32].…”

Tuberculosis infection: Insight from immunogenomics

“…Rather than providing a comprehensive review, we will highlight factors that may influence partial immunity to MTb and how modulation of the innate immune response may be incorporated into future MTb vaccines and therapeutic strategies. In-depth review of subtopics within this manuscript include work on the immune response to Tb [2,3], genetic influences on Tb susceptibility [4][5][6][7], and the innate immune response [8][9][10].…”