Leprosy immunopathogenesis and vaccine development

The truly effective immunity against intracellular parasites, including mycobacteria, is mediated by monocyte/macrophages, and in the immunologically responding (resistant) host these phagocytes need minimal antigenic stimulus, specific or non-specific, to become activated and be microbicidal. T-cell mediated delayed hypersensitivity (DTH) causes tissue damage and destruction, which is particularly unwelcome in leprosy because of its nerve-damaging potential. Gamma interferon (INF-gamma), the terminal lymphokine of a DTH response, promotes mycobacterial survival and growth. There are T-cells (TH1 subtypes) that produce DH response either independent of, or, only partly dependent on INF-gamma; this type of DH peaking at 24 hours appears similar to the Jones-Mote type rather than to the tuberculin type of DTH peaking at 48-72 hours and is devoid of the necrotic component of tuberculin type of DTH. M. leprae antigens normally elicit this Jones-Mote type of DH. Suppressor T-cells are associated with a protective immune response, while helper T-cells mediating DTH are harmful. In view of this immunobiology, it would appear that pathogenic mycobacteria that generate a tuberculin type DTH response should not be used as immunogens in leprosy.