INDUCTION OF IMMUNITY AND TOLERANCE TO M LEPRAE

这项研究有两个主要目标： (1)评价正常Lewis大鼠的免疫应答。 热灭活麻风杆菌皮内免疫及其与 热灭活麻风杆菌加活卡介苗，使用体外技术 细胞免疫功能(CMI)的评估。免疫系统的特性 皮内给药后产生的反应 疫苗进入正常的Lewis大鼠将基于：(A)动力学(开始 和持续时间)发育中的免疫反应，(B)抗原阈值 (C)效率(速度和水平) 发展)和继发性免疫回忆的持续时间 用麻风杆菌热灭活抗原和活的VCG免疫。入内 用于评估CMI表达的体外参数 体内抗原致敏的脾和淋巴结细胞与M。 麻风和PPD将是：(A)特异性抗原诱导的淋巴细胞 (B)迁移抑制因子的释放；(C) 白介素2的产生。体外测定的CMI水平 分析，将与体内的抗药性水平进行比较 用存活的麻风杆菌挑战。 (2)探讨M。的免疫机制(S)。 用体外方法诱导Lewis大鼠对麻风的耐受 抗原特异性淋巴细胞活化的评估。的作用 巨噬细胞、淋巴细胞和血清因子将在体外进行检测。 在活体内。耐药的Lewis大鼠的脾和淋巴结细胞。 麻风抗原将被检测其产生不同种类的 淋巴因子(白介素2、迁移抑制因子、巨噬细胞 激活因子和干扰素)和细胞因子(白介素1) 与麻风杆菌抗原、PPD和ConA共培养后， 将进行实验以确定麻风杆菌诱导的耐受性 结果通过活体挑战活体M。 麻风病。 这项研究的结果可能被证明对设计未来的临床有用 抗麻风疫苗的试验，并可能提供有价值的信息 关于CMI功能障碍的免疫学机制 以人类麻风为特征的。我们的长期目标是 开发一种免疫和化疗联合治疗麻风的方法 可应用于临床。

This research has two main objectives: (1) To evaluate the immune response of normal Lewis rats following intrasdermal immunization with heat-killed M. leprae and a combination of heat-killed M. leprae plus viable BCG, using in vitro techniques for assessment of cell-mediated immunity (CMI). Characterization of the immune response that develops following intradermal administration of the above vaccines into normal Lewis rats will be based on: (a) the kinetics (onset and duration) of the developing immune response, (b) the antigen threshold required for its induction, and (c) the efficiency (rate and level of deveopment) and duration of immunological recall following secondary immunization with heat-killed M. leprae antigens and viable VCG. The in vitro parameters to be used for assessment of CMI expreession following co-culture of in vivo antigen-primed spleen and lymph node cells with M. leprae and PPD will be: (a) specific-antigen-induced lymphocyte proliferation, (b) release of migration inhibition factor, and (c) production of interleukin-2. The level of CMI, as measured by in vitro analysis, will be compared with the level of in vivo resistance by challenge with viable M. leprae. (2) To investigate the immunological mechanism(s) responsible for M. leprae-induced tolerance in the Lewis rat using in vitro methods for assessment of antigen-specific lymphocyte activation. The role of macrophages, lymphocytes, and serum factors will be examined both in vitro and in vivo. Spleen and lymph node cells from Lewis rats tolerant to M. leprae antigens will be examined for their ability to produce various lymphokines (interleukin-2, migration inhibition factor, macrophage activating factor, and interferon) and a cytokline (interleukin-1) following co-culture wit M. leprae antigens, PPD and Con A. Finally, experiments will be conducted to determine if M. leprae-induced tolerance results in decreased resistance using in vivo challenge with viable M. leprae. Results from this study may prove useful for designing future clinical trials with antileprosy vaccines and may provide valuable information concerning the immunological mechanisms responsible for the CMI dysfunction characteristic of lepromatous leprosy in humans. Our long-term goal is to develop a combined immuno- and chemotherapeutic treatment of leprosy that could be applied clinically.