IMMUNOLOGICAL MECHANISM OF INFLAMMATION IN UVEITIS & EAE

描述(摘自申请者的摘要)：葡萄膜炎是一组 炎症性眼病可能由感染、恶性肿瘤、 创伤，或不完全理解的过程，据推测是由 身体的免疫系统。在许多情况下，葡萄膜炎与 身体其他部位的潜在炎症性疾病过程。葡萄膜炎 也可能与多发性硬化症(MS)有关，其中中枢 神经系统(CNS)炎症与 眼睛。在这些研究中，建议澄清两者之间的关系 眼睛和中枢神经系统的炎症，这可能给出关于 这种炎症性疾病的发生机制。它还可以提供 一种研究人类并发症眼部炎症的有用模型 全身性疾病。出于这个原因，建议使用动物模型 用于MS-EAE。与一些多发性硬化症患者类似，动物也会发生 与眼部炎症有关的眼部炎症 脊髓。在Lewis大鼠中，第二剂可再次诱发葡萄膜炎 髓鞘碱性蛋白(MBP)。因此，该动物模型允许 复发性葡萄膜炎的机制研究，这在人类中导致 永久性组织损伤和失明。建议测试一下 存在共同的致病自身免疫机制的假设 在眼睛和中枢神经系统的炎症中，包括共同的靶抗原。 因此，在所提出的模型中，MBP特异性T细胞在 引发葡萄膜炎以及葡萄膜炎复发的事件 眼部发炎。申请者假设不仅细胞，而且 此外，将这些细胞吸引到眼睛的因素也是 致病过程。阐明相关的免疫学机制 在葡萄膜炎的发病机制上，他们提出了以下具体目标： (1)确定针对目标抗原的免疫反应的特异性 免疫后同时发生前葡萄膜炎和EAE的Lewis大鼠 与MBP合作。(2)明确T细胞在Lewis复发性葡萄膜炎中的作用 用MBP复查大鼠。(3)研究细胞因子的作用和 趋化因子在原发和复发性眼部细胞募集中的作用 Lewis大鼠MBP免疫后并发EAE的葡萄膜炎

DESCRIPTION (Adapted from applicant's abstract): Uveitis is a group of inflammatory eye diseases that may result from infections, malignancies, trauma, or incompletely understood processes that are presumably mediated by the body's immune system. In many cases, uveitis is associated with underlying inflammatory disease processes elsewhere in the body. Uveitis may be also associated with multiple sclerosis (MS) where the central nervous system (CNS) inflammation is associated with the inflammation of the eye. In these studies, it is proposed to clarify the relationship between inflammation in the eye and in the CNS, which may give a clue about the mechanism of development of this inflammatory disease. It may also provide a useful model for studying an eye inflammation as a complication of human systemic disorders. For this reason, it is proposed to use an animal model for MS-EAE. Similarly to some patients with MS, animals develop inflammation of the eye that is associated with the inflammation of the spinal cord. In Lewis rats, uveitis can be re-induced with the second dose of myelin basic protein (MBP). Therefore, this animal model permits the study of the mechanism of relapsing uveitis, which in humans leads to permanent tissue damage and blindness. It is proposed to test the hypothesis that there are common pathogenic autoimmune mechanisms involved in inflammation of the eye and the CNS, including common target antigens. Thus, in the proposed model, MBP-specific T cells play a role in the initiation of the events leading to uveitis as well as in the recurrence of eye inflammation. The applicants hypothesize that not only the cells but also factors that attract those cells to the eye are important components of the pathogenic process. To elucidate the immunological mechanism involved in the pathogenesis of uveitis, they propose the following specific aims: (1) Determine specificity of the immune response for a target antigen in Lewis rats which develop both anterior uveitis and EAE after immunization with MBP. (2) Define the role of T cells in the recurrent uveitis in Lewis rats upon re-examination with MBP. (3) Examine the role of cytokines and chemokines in the recruitment of cell to the eye in primary and recurrent uveitis associated with EAE after immunization of Lewis rats with MBP.