Immunotherapy and immunoprophylaxis of leprosy

Abstract

The clinico-pathologic spectrum ofleprosy in its diverse fo rms is the expression of the immunologic response of the human host to infection by My cobacterium leprae.In this spectrum, the ' lepromatous pole is characterized by a total lack of cell-mediated effector immunological responses; this lack is also seen to a lesser degree in borderline lepromatous (BL) as well as in other fo rms, which present a variable degree of deficiency of this type of immunity as they are located along the spectrum towards the tuberculoid pole of the disease.There is substantial evidence that the immunological defect which reaches its maximum expression in lepromatous patients is also present in other population groups, including a small portion of the healthy population. This evidence includes the fo llowing observations: (a) A significant proportion of patients with the indeterminate form of leprosy show immunological behaviour similar to that of the lepromatous patient, characterized by a lack of cell-mediated manifestations toward M. leprae. Without adequate treatment, this indeterminate form of leprosy shows a tendency to progress to lepromatous leprosy (LL). We have seen this phenomenon of progression towards the LL pole in indeterminate patients who, after many years of treatment, have stopped their medication due to various reasons and suddenly re-appear with LL or BL disease. On the other hand, indeterminate lesions in Mitsuda-positive patients show a tendency to regress spontaneously, or to evolve towards the highly resistant fo rms of the disease.' (b) Studies of the Mitsuda reaction in the general population, both in endemic and non-endemic areas, show that a small proportion of the general population is persistently Mitsuda-negative. In 1978 we studied the persist ence of this negativity towards lepromin in the population of a non-endemic area of Venezuela and found that 1·25% of the general population remained

Immunological suppression by human CD8+ T cells is receptor dependent and HLA-DQ restricted.

“…In the case of unresponsiveness in infectious diseases such as lepromatous leprosy, it is unlikely that the T-cell clones to the multiplicity of antigens of a bacterial pathogen could all be deleted neonatally, long prior to infection. As noted above, a majority of such patients can be immunized therapeutically to clinically upgrade their immune responses to M. Ieprae and, in some cases, cure their infection (11). Lymphocytes from a third of lepromatous patients studied, although unresponsive to intact M. leprae, have been reported to be able to respond to electrophoretic fractions of M. leprae extracts (26).…”

“…It is in this context that leprosy is of fundamental immunological interest, because it is a chronic human infectious disease in which a significant proportion of patients, those with the lepromatous form of the disease, fail to develop detectable cell-mediated immunity to antigens of Mycobacterium leprae. In the majority of lepromatous patients, the unresponsiveness is not irreversible, since it has been possible to overcome the unresponsiveness in the majority of the lepromatous patients using immunotherapeutic vaccines (11)(12)(13). Leprosy therefore provides a relatively unique model in humans for studying peripheral tolerance.…”

Lepra Vaccine

“…This belies the use of vaccines in leprosy 3 . The rationale of immunotherapy with M. w is that it May boost cell‐mediated immunity and thus lead to increased clearance of bacilli 4,5 . Studies that prove this basis, their findings on bacterial index, mouse food inoculation studies, and lepromin conversion are contributary 3–5 .…”

“…The rationale of immunotherapy with M. w is that it May boost cell‐mediated immunity and thus lead to increased clearance of bacilli 4,5 . Studies that prove this basis, their findings on bacterial index, mouse food inoculation studies, and lepromin conversion are contributary 3–5 . These studies of surrogate markers suggest that a theoretical basis behind immunotherapy is sound, but whether it can translate into significant clinical improvement remains an enigma.…”

Desenvolvimento de preparado antigênico Mitsuda-símile e sua avaliação em pacientes multibacilares Mitsuda-negativos

“…Previous studies used different antigen preparations to induce immune responses in anergic leprosy patients. 6,9,10 The author's data suggest that a Mitsudalike antigen prepared from the microorganism cultivated could be efficient to induce an immune response to the Mitsuda antigen. To test this hypothesis, Mitsuda-like antigen C12-004 was prepared and inoculated in anergic leprosy patients, and its effects on the immune response induction were assessed by a subsequent Mitsuda test.…”