CHARACTERIZATION OF EXPERIMENTAL LEPROSY

我们已经展示了长尾猴(Cecocbus Atys Atys)是 实验性麻风的研究。恒河猴(猕猴)和非洲绿 (Cercopithecus Atheiops)猴子也有可能患上这种疾病 麻风病。 这项建议的目标是：1)继续临床研究， 在免疫学和组织病理学上，未经治疗和经治疗的曼加比， 进一步明确了恒河猴和非洲绿猴的麻风病程； 2)接种额外的恒河猴和绿猴，以确定它们的 对实验性麻风的易感性；3)研究 免疫调节剂(胸腺生成素、白介素2、干扰素、卡介苗 杀死麻风分枝杆菌和可能的转移因子)；4)定义 乐普宁皮试与易感性及病程的关系 5)进一步研究免疫机制。 我们在麻风病人身上观察到的抑制；6) 确定是否可以通过接种麻风杆菌疫苗来保护芒果蜂 抗活麻风杆菌攻击的抗原；以及7)维持 建立燕麦繁殖群，为麻风提供动物 研究。 动物将受到纵向监测，就像我们以前和 在接种疫苗或接种或治疗之后。我们会完全 在接种疫苗前、接种后和接种后每隔一段时间描述动物的特征 麻风杆菌接种，并在治疗期间。研究将包括：血清 化学和血象；物理、临床和神经学检查；神经 传导速度；细菌学、组织病理学和免疫组织学 活组织检查。待研究的免疫学参数包括： 淋巴细胞的体外有丝分裂原和抗原(如Leproin)反应(L)； L免疫球蛋白(Ig)的体外生产；B-和T-L数和 亚群；抑制/辅助T-L活性；自然杀伤(NK)细胞 细胞毒性和抗体依赖性细胞毒性；血液 单核细胞环磷酸腺苷、磷酸二酯酶和腺苷环化酶水平； Leproin皮试反应；血清Ig、C3、C4、免疫水平 复合体、前列腺素、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； 进一步阐明猴子的麻风病过程；显示是否 免疫疗法可以改变麻风病的病程；并确定 接种疫苗可提供保护，防止麻风实验性传播 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.