Immunology of tuberculosis and implications in vaccine development

Mycobacterium tuberculosis is a very successful pathogen that can survive and persist in the human host in the face of a robust immune response. This immune response is sufficient to prevent disease in the majority of infected persons, providing compelling evidence that immunity to tuberculosis is possible. However, it is more striking that the strong immune response is not generally effective at eliminating the organisms, during either initial infection or the persistent or latent phase of infection. Studies in animal models and in humans have demonstrated the wide range of immune components involved in the effective response against M. tuberculosis. These components include T cells (both CD4+ and CD8+), cytokines, including IFN-gamma, IL-12, TNF-alpha, and IL-6, and macrophages. The precise roles and functions of these cells and molecules (and others) are still being defined and may differ in acute and chronic infection. These immune responses are directed towards containing or eliminating the tubercle bacillus within the tissues of the host. The estimated eight million new cases of tuberculosis each year clearly demonstrate that these responses are not always effective. M. tuberculosis has obviously evolved a variety of mechanisms to evade destruction by the immune response. Studying both the host and the pathogen will elucidate potential vaccine candidates. In this review, the known functions of immune components in the response to M. tuberculosis and implications for vaccine development will be discussed.