Date of Award

1989

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Edward J. Shannon

Abstract

The nine-banded armadillo (Dasypus novencinctus linn.) is highly susceptible to infection with M. leprae and has become an important animal model in the study of leprosy. In an attempt to define the major immunogens of M. leprae and the isotypic antibody response to these molecules during infection, the IgG and IgM antibody responses of experimentally-infected armadillos to the sonicated M. leprae, supernatant fraction of sonicated M. leprae, lipoarabinomannan derived from M. tuberculosis, and phenolic glycoliopid-I was analyzed using immunoblot and ELISA. Antibodies to the specific epitope (defined by monoclonal antibody IIIE9) on the 65-kDa protein of M. leprae were analyzed using a competitive antibody binding assay. Our results showed that protein antigens of M. leprae elicited a predominant IgG antibody response, whereas, carbohydrate antigens of M. leprae, including liporarbinomannan, induced an IgM response. Phenolic glycolipid-I elicited both IgG and IgM antibody responses. Some animals produced and maintained a strong IgG antibody response to phenolic glycolipid-I which correlated with their ability to delay dissemination of the infection and with their ability to survive infection for longer periods of time. Antibodies to an M. leprae specific epitope on the 65-kDa protein in crude cell wall extracts but not to the recombinant 65-kDa protein were detected during the later stage of infection in both armadillos and leprosy patients. The lack of concordance between CABA's developed with the crude native antigen and those developed with the purified recombinant 65-kDa protein is suggestive of false-positive results, possibly induced by steric hindrance, being associated with CABA which incorporate crude cell wall extracts as antigen source. Therefore, the IIIE9 epitope of M. leprae does not appear to be immunogenic in the armadillo or the leprosy patient. It was shown that antibody profiles to various M. leprae antigens proved useful in monitoring the course and outcome of infection in armadillos as well as establishing baseline information on the humoral immune response in armadillos during the course of an untreated infection with M. leprae.

Pages

113

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