MECHANISMS OF ANTIMYCOBACTERIAL IMMUNITY

Mycobacterium tuberculosis is a facultative intracellular parasite whi ch can grow within mononuclear pha,oocytes. In mice, antimycobacterial immunity appears to require the coordinated activity of a wide range of T cell and macrophage functions, including the activity of TCR alph a beta(+), CD4(+) and CD8(+) T cells as well as TCR gamma delta(+) T c ells. Cytokines especially interferon-gamma (IFN-gamma), tumour necros is factor-alpha (TNF-alpha) and IL-12, as well as the induction of nit ric oxide production within activated macrophages are also crucial for effective antimycobacterial immunity. In mice, DNA vaccines utilizing phage vectors encoding one of several mycobacterial antigens confer p rotective immunity, although immunization with these proteins per se f ails to do so. Hence it is not the nature of the antigen or the epitop es which are recognized that is relevant to the induction of effective immunity, but the T cell circuits that are activated by such a proced ure. In addition to T cell recognition of protein antigens, recent wor k has shown that certain T cell subsets can recognize non-peptide anti gens, such as mycolic acid and lipoarabinomannan, presented to T cells by CD1 antigens. Although the components of human antimycobacterial i mmunity are broadly similar to those of mice, there are significant di fferences in detail which are discussed in this review.