INDUCTION OF IMMUNITY TO MYCOBACTERIUM LEPRAE

麻风分枝杆菌是一种专性的细胞内寄生虫 是麻风病的病原体，麻风病是一种折磨人的疾病 全球约有1500万人。麻风杆菌有能力 在巨噬细胞中增殖，并可入侵并在 周围神经鞘中的雪旺细胞。在病人中 对于类结核麻风，对M。 麻风病仍然完好无损，这些个体的病毒滴度很低 循环抗体，但麻风杆菌细胞几乎是 检测不到。另一方面，麻风病患者 具有独特的细胞免疫抑制作用。 麻风，具有高滴度的麻风杆菌循环抗体， 并且有非常高的细菌载量。使用重组 技术，我们已经确定了表达M. 与麻风病人血清中的抗体反应的麻风蛋白抗原 麻风患者中既有麻风患者也有结核样麻风患者。我们还有 开发出一些独特的无毒沙门氏菌菌株，这些菌株能够 稳定维持和表达定植和毒力抗原 来自其他病原体。口服后，沙门氏菌就会回到家 肠道相关淋巴组织(GALT)以诱导分泌， 体液和细胞免疫反应。因此，我们建议 (I)进一步确定麻风杆菌的决定因素并确定其特征 由可识别的重组大肠杆菌表达 麻风和/或结核样麻风患者血清中的抗体 患者，(Ii)构建鼠伤寒沙门氏菌的无毒衍生物以 稳定表达麻风杆菌特异性抗原决定簇和(Iii) 这些无毒重组鼠伤寒沙门氏菌免疫小鼠 评价分泌物、体液的质量和持续时间的菌株 以及对麻风杆菌的细胞免疫反应。后续 这项工作将研究免疫抑制的诱导， 细胞免疫反应的细胞和分子基础，以及 使用其他动物系统评估诱导 对麻风杆菌感染的保护性免疫。研究方法： 生物化学、免疫学、遗传学、显微镜和动物 科学将被用于这些研究。

Mycobacterium leprae is an obligate intracellular parasite that serves as the etiologic agent of leprosy, a disease that afflicts some 15 million individuals worldwide. M. leprae is capable of multiplication in macrophates and can invade and multiply in the Schwann cells in the sheaths of peripheral nerves. In patients with tuberculoid leprosy, the cellular immune response to M. leprae remains intact and these individuals have low titers of circulating antibodies but M. leprae cells are virtually undetectable. Patients with lepromatous leprosy, on the other hand, have a unique suppression of cellular immunity against M. leprae, have high titers of circulating antibody against M. leprae, and have a very hgih bacteriological load. Using recombinant techniques, we have identified cloned genes that express M. leprae protein antigens that react with antibodies in the sera of both lepromatous and tuberculoid leprosy patients. We have also developed some unique avirulent Salmonella strains that are able to stably maintain and express colonization and virulence antigens from other pathogens. Upon oral ingestion, the Salmonella home to the gut-associated lymphoid tissue (GALT) to elicit secretory, humoral and cellular immune responses. We therefore propose to (i) further identify and characterize M. leprae determinants expressed by recombinant Escherichia coli that are recognized by antibodies in sera from lepromatous and/or tuberculoid leprosy patients, (ii) construct avirulent derivatives of S. typhimurium to stably express specific M. leprae antigenic determinants and (iii) immunize mice with these avirulent S. typhimurium recombinant strains to evaluate the quality and duration of secretory, humoral and cellular immune responses against M. leprae. Subsequent work will investigate the induction of immune suppression, the cellular and molecular basis of the cellular immune response, and the use of other animal systems to evaluate induction of protective immunity against M. leprae infection. The methods of biochemistry, immunology, genetics, microscopy, and animal science will be employed in these studies.