SIGNIFICANCE OF IMMUNOLOGICAL SEQUESTRATION IN THE EYE

描述(改编自申请者的摘要)：一个持久的问题 在眼免疫学中认为隔离在维持 视网膜的免疫特免权。封存指的是被动的 免疫耐受是由于抗原位于 生理和解剖障碍，尤指神经系统中的障碍。这个 视网膜血管内皮细胞和色素上皮细胞已经提出 通过形成屏障来抑制传入和传出免疫过程 导致淋巴细胞渗漏和蛋白质渗漏。此外，II级 MHC在隔离部位的表达受到限制，进一步抑制 生产性T细胞抗原受体占有率。虽然是最近的 调查显示，存在诱导机制 从理论上讲，主动耐受性可以提供免疫特权，他们的 在未受刺激的正常宿主中没有表现出活性。那 差异是这一建议的精髓：了解眼睛免疫 在活跃的眼睛机制尚未被激活的动物中享有特权 通过将抗原或细胞因子注射到眼房隔中而引起的。 申请者将通过两种策略分析自动减支的作用。 一种方法是利用细菌抗原的差异表达。 转基因小鼠体内的β-半乳糖苷酶。另一种方法使用 逆转录病毒基因转移产生一种已知的系统性表达 葡萄膜生成抗原、芦荟素或S抗原(S抗原)，允许这种作用 使免疫系统暴露在具有良好特征的、非隔离的 S-银待评估。这些策略提供了可控的 解决眼睛免疫学中一个基本问题的机会， 并加强我们对免疫机制的理解 维持对葡萄膜原性视网膜抗原的耐受性。

DESCRIPTION (Adapted from applicant's abstract): An enduring question in ocular immunology regards the role of sequestration in maintaining the immune privilege of the retina. Sequestration refers to the passive immune tolerance that is due to antigens being located behind physiologic and anatomic barriers, especially in the nervous system. The retinal vascular endothelium and pigment epithelium have been proposed to inhibit afferent and efferent immune processes by forming barriers to lymphocytic perusal and leakage of proteins. In addition, class II MHC expression is limited in sequestered sites, further inhibiting productive T cell antigen receptor occupancy. Although recent investigations have revealed the presence of inducible mechanisms of active tolerance that could, in theory, provide immune privilege, their activity has not been demonstrated in unstimulated, normal hosts. That difference is the essence of this proposal: to understand ocular immune privilege in animals where active, ocular mechanisms have not been induced by injection of antigens or cytokines into ocular compartments. The applicant will analyze the role of sequestration by two strategies. One approach uses the differential expression of the bacterial antigen beta-galactosidase, in transgenic mice. The other approach uses retroviral gene transfer to produce systemic expression of a known uveitogenic antigen, arrestin or S-antigen (S-Ag), allowing the effect of exposing the immune system to a well-characterized, non-sequestered S-Ag to be assessed. These strategies provide well-controlled opportunities to address a fundamental question in ocular immunology, and enhance our understanding of immune mechanisms responsible for maintaining tolerance to otherwise uveitogenic retinal antigens.