CHARACTERIZATION OF EXPERIMENTAL LEPROSY

我们已经证明白眉猴（Cecocebus atys atys）是一个模型， 实验性麻风病的研究 恒河猴（Macaca mulatta）和非洲绿色 （Cercopithecus aethiops）猴子也表现出对 麻风病 本提案的目标是：1）继续临床研究， 免疫学和组织病理学未处理和处理的白眉猴， 恒河猴和非洲绿色猴，以进一步确定麻风病的病程; 2)以增加恒河猴和绿色猴的数量， 对实验性麻风的易感性; 3）研究 免疫调节剂（胸腺生成素、白细胞介素2、γ-干扰素、BCG + 杀死麻风分枝杆菌和可能的转移因子）; 4）确定 麻风菌素皮试与麻风易感性及病程的关系 5）进一步研究麻风病免疫机制， 我们在患有麻风病的白眉猴中观察到的抑制; 6） 确定是否可以通过接种M.麻风 抗活M.麻风病;和7）保持 建立了YRPRC白眉猴繁殖群，为麻风病提供动物 research. 将对动物进行纵向监测，就像我们之前一直在做的那样， 接种疫苗或治疗后。 我们将彻底 在接种前和接种后间隔以及接种后 M.麻风病接种和治疗期间 研究将包括：血清 化学和血象;体格、临床和神经系统检查;神经 传导速度;细菌学、组织病理学和免疫组织学 活检检查。 待研究的免疫学参数为： 体外有丝分裂原和抗原（例如，淋巴细胞（L）的反应; 体外L免疫球蛋白（IG）产生; B-和T-L数量， 亚群;抑制/辅助性T-L活性;自然杀伤细胞 细胞毒性和抗体依赖性细胞毒性（ADCC）;血液 单核细胞环AMP、磷酸二酯酶和腺苷酸环化酶水平; 麻风菌素皮肤试验反应;血清IG、C3、C4、免疫 复合物、洋地黄素、唾液酸、类风湿因子和抗M. 麻风抗体 这些研究将进一步确定猴子对麻风病的易感性; 进一步阐明麻风病在猴子中的过程;显示是否 免疫疗法可以改变麻风病的病程;并确定是否 接种疫苗可防止实验性麻风病传播 在猴子身上。

We have shown mangabey monkeys (Cecocebus atys atys) to be a model for the study of experimental leprosy. Rhesus (Macaca mulatta) and African green (Cercopithecus aethiops) monkeys show promise of also being susceptible to leprosy. The goals of this proposal are: 1) to continue to study clinically, immunologically and histopathologically untreated and treated mangabeys, rhesus and African green monkeys to further define the course of leprosy; 2) to inoculate additional rhesus and green monkeys to define their susceptibility to experimental leprosy; 3) to study the effects of immunomodulators (thymopoietin, interleukin 2, gamma-interferon, BCG + killed Mycobacterium leprae and possibly transfer factor); 4) to define the relationship of lepromin skin testing to the susceptibility to and course of leprosy in monkeys; 5) to further characterize the mechanism of immune suppression that we have observed in mangabeys with leprosy; 6) to determine if mangabeys can be protected by vaccination with M. leprae antigens against challenge with live M. leprae; and 7) to maintain the established YRPRC mangabey breeding colony to provide animals for leprosy research. Animals will be monitored longitudinally, as we have been doing, before and after vaccination or inoculation or treatment. We will completely characterize animals prior to and at intervals after vaccination and after M. leprae inoculation, and during therapy. Studies will include: serum chemistries and hemograms; physical, clinical and neurological exams; nerve conduction velocities; bacteriologic, histopathologic and immunohistologic examinations of biopsies. Immunologic parameters to be studied are: in vitro mitogen and antigen (e.g., lepromin) responses of lymphocytes (L); in vitro L immunoglobulin (Ig) production; B- and T-L numbers and subpopulations; suppressor/helper T-L activity; natural killer (NK) cell cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC); blood mononuclear cell cyclic-AMP, phosphodiesterase and adenyl cyclase levels; lepromin skin test responses; serum levels of Ig's, C3, C4, immune complexes, prostaglandins, sialic acid, rheumatoid factor, and anti-M. leprae antibody. These studies will further define the susceptibility of monkeys to leprosy; further illuminate the course of leprosy in monkeys; show whether immunotherapy can alter the course of leprosy; and determine whether vaccination may offer protection against experimental leprosy transmission in monkeys.