The three stages of tuberculosis.

<p><b>Stage 1</b>: Infection of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) frequently occurs at a young age. Metabolically active <i>Mtb</i> are inhaled and subsequently T-cells are stimulated which carry the major burden of acquired immunity. These include major histocompatability complex class II (MHC II)-restricted CD4 T-cells and MHC I-restricted CD8 T-cells. B cells are also activated but their protective role in TB remains elusive. Pre-exposure vaccines are given at this early stage. Novel pre-exposure vaccine candidates are given very soon after birth and thus generally before infection with <i>Mtb</i>. They either substitute for Bacille Calmette Guérin (BCG) or boost immunity induced by BCG. <b>Stage 2</b>: Acquired immunity comprising CD4 and CD8 T-cells contains <i>Mtb</i> in a dormant stage within solid granulomas. T-cells produce type I cytokines and cytolytic effector molecules. They become memory T-cells which concomitantly produce multiple cytokines. Individuals remain latently infected without clinical signs of active tuberculosis (TB). Post-exposure vaccines are given to adolescents or adults who are latently infected but healthy. <b>Stage 3</b>: Mechanisms leading to deficient immunity and disease reactivation are numerous and include production of suppressive cytokines such as interleukin (IL)-10 and transforming growth factor-beta (TGFβ) by T helper 2 (Th2) cells and regulatory T(reg) cells as well as T-cell exhaustion mediated by inhibitory receptor-coreceptor interactions on antigen presenting cells (APCs) and T-cells. <i>Mtb</i> becomes metabolically active and granulomas become caseous. <i>Mtb</i> can be spread to other organs and to other individuals. Therapeutic vaccines are given to TB patients in adjunct to chemotherapy.