Leprosy is a chronic infectious disease caused by Mycobacterium leprae. As with other intracellular parasites, protective immunity is dependent on T cells and cell-mediated immunity. In animal models, immunization with killed armadillo-derived M. leprae elicits strong T-cell responses, delayed-type hypersensitivity and protection against viable challenge. We have recently shown that killed M. leprae can induce delayed-type hypersensitivity in healthy human volunteers. Identification of the M. leprae antigens that are recognized by T cells and may be involved in protection has been hampered by the inability to cultivate the organism in vitro and by difficulties in antigen purification from limited quantities of armadillo-derived bacillus. Because genes for the major protein antigens of M. leprae as seen by mouse monoclonal antibodies have been isolated, it has become possible to test whether these individual antigens are recognized by T cells. We screened crude lambda gtll phage lysates of Escherichia coli containing individual M. leprae antigens using M. leprae-specific T-cell clones isolated from M. leprae-vaccinated volunteers. Using this method, we find that nearly half of the M. leprae-specific T-cell clones are stimulated to proliferate by lysates containing an epitope of a M. leprae protein of relative molecular mass 18,000 (18K).

Antibodies, Monoclonal↗

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Selective primary health care: strategies for control of disease in the developing world. V. Leprosy.

Leprosy afflicts 10-15 million people in the world, primarily in tropical and subtropical developing countries. In areas endemic for leprosy, the incidence may reach four to six cases per 1,000 population, and the prevalence of the disease frequently exceeds 10 per 1,000 population in parts of Africa and Asia. While these figures are not high in relation to those for other tropical diseases, many developing countries consider leprosy a major health problem because a significant proportion of cases result in deformity and subsequent social stigmatization. Leprosy comprises a wide spectrum of clinical and pathologic stages that have been classified histopathologically. In polar lepromatous disease there is specific immunologic unresponsiveness of cell-mediated immunity to Mycobacterium leprae antigens, while, in the tuberculoid form of the disease, strong cell-mediated immunity is present but tissue damage seems to be a consequence. This review discusses the detailed immunologic analyses of the histopathology and pathogenesis of the various stages of leprosy. It will be argued that lepromatous leprosy presents an extraordinary model for understanding the mechanisms of immunologic unresponsiveness in humans. The present effectiveness and limitations of chemotherapy in the face of emerging resistance to dapsone are briefly discussed. Recent advances in the development of vaccines are discussed in terms of their immunologic potential and epidemiologic necessity. The implications of an effective prophylactic or immunotherapeutic vaccine used in combination with chemotherapy are also presented.

BCG Vaccine↗

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