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.

Growth of Mycobacterium leprae in a redox system: III. Evidence of growth at low temperature (psychrophilia) and, further refinement of growth medium.

Considerable growth enhancement, largely as non-acid fast, slender and long rods has been seen when incubated at 10 degrees C. Concentration of some of the media constituents have been reduced that has improved the quantum of growth. A remarkable proneness to physical disintegration of the grown bacilli has been seen and its significance discussed. Also, the possible immunogenic advantage of non-AF M. leprae has been discussed. The question of identification is still not solved, and work is in progress.

Growth of Mycobacterium leprae in a redox system: II. Further improvements in the system and growth efficiency.

Improvement of the Redox System for growth of M. leprae as brought about by modification in the concentration and mode of preparation of individual media constituents, and by addition of newer substances, is being reported. A structural modification in the construction of the Thunberg's tubes and flasks that are used as culture vessels, has been introduced for ease of handling. Vitamin E (alpha-tocopherol) has been found to be useful. Concentrations of Liposomes and Gelatin in the medium could be reduced by at least five folds, considerably easing thereby smearing and harvesting of cultures. Dimercaptopropanol British Anti-lewisite or BAL) has been used, but its usefulness or otherwise is yet to be determined conclusively. The basis of intracellular parasitism of M. leprae has been discussed.