ANTIBODY INDUCTION AND EXPRESSION IN THE EYE

眼睛中抗体的诱导和表达

• 批准号: 6240140
• 负责人: Paul C. Montgomery
• 金额: $ 2.69万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240140
• 关键词: T cell receptor; antibacterial antibody; conjunctiva; electron microscopy; eye; gene expression; gene induction /repression; immunocytochemistry; immunoglobulin A; laboratory rat; lacrimal apparatus; light microscopy; mucosal immunity; nonhuman therapy evaluation; topical drug application

The long-term objectives of this study are to define the specific regulatory processes governing ocular mucosal-associated immune responses and provide basic information applicable to the design of clinically relevant immunization protocols. The overall hypotheses to be tested are; 1. that antigen dissemination and the traffic of specific lymphoid populations play major roles in the induction of tear IgA antibody responses following ocular topical immunization; 2. that certain cytokines play key roles in the induction and expression of tear IgA antibodies; and 3. that specific lymphocyte receptors and acinar cell ligand molecules mediate the selective localization of lymphoid populations within lacrimal gland tissues. The specific aims to test these hypotheses are: AIM 1. To define the regulatory events leading to IgA antibody induction and expression in tears after ocular topical stimulation. This aim will compare the kinetics of antigen distribution and examine cell traffic to lacrimal gland and conjunctiva following ocular topical immunization, AIM 2. To determine the role of cytokines in the induction and expression of tear IgA antibodies. This aim will determine the levels and functional significance of endogenous cytokines in ocular mucosal tissues and test the use of biodegradable microparticles as an ocular delivery vehicle for antigen and/or IgA enhancing cytokines. Aim 3. To characterize the molecules responsible for lymphocyte interactions with lacrimal gland acinar epithelial cells. This aim will examine the molecular structure of the lymphocyte receptor and determine the biochemical nature of the acinar epithelial cell ligand. Experimentation will use the rat model, which has a well-characterized ocular mucosal immune system. To achieve these aims, light and electron microscopy, cell isolation, cell and organ fragment cultures, flow cytometry, hybridoma production and in vitro adherence methods will be employed in conjunction with immunochemical, biochemical and molecular analyses. Overall, these investigations will provide a more complete understanding of the events involved in the regulation of ocular mucosal-associated antibody induction and identify new approaches to generate and control immune responses at the ocular surface.

这项研究的长期目标是定义特定 控制眼粘膜相关免疫反应的调节过程 并提供适用于临床设计的基本信息 相关免疫方案。 要测试的总体假设是； 1。抗原传播和特定淋巴机的流量 种群在诱导泪液IGA抗体中起着重要作用 眼部局部免疫后的反应； 2。某些细胞因子 在撕裂Iga抗体的诱导和表达中发挥关键作用；和 3。特定的淋巴细胞受体和腺泡细胞配体分子 调解淋巴样种群在泪中的选择性定位 腺组织。 检验这些假设的具体目的是：目标1。 定义导致IGA抗体诱导和的调节事件 眼部局部刺激后的眼泪表达。 这个目标 比较抗原分布的动力学并检查细胞流量 眼部局部免疫后泪腺和结膜 2。确定细胞因子在诱导和表达中的作用 撕裂IgA抗体。 这个目标将决定水平和功能 内源性细胞因子在眼粘膜组织中的重要性并测试 使用可生物降解的微粒作为眼部输送车 抗原和/或IgA增强细胞因子。 目标3。要表征 负责淋巴细胞相互作用与泪腺相互作用的分子 腺泡上皮细胞。 这个目标将检查 淋巴细胞受体并确定腺泡的生化性质 上皮细胞配体。 实验将使用大鼠模型，该模型具有 特征良好的眼粘膜免疫系统。 为了实现这些目标， 光和电子显微镜，细胞分离，细胞和器官片段 培养物，流式细胞术，杂交瘤产生和体外粘附 方法将与免疫化学，生化一起使用 和分子分析。 总体而言，这些调查将提供更多 完全了解眼管调节的事件 粘膜相关抗体诱导并确定新方法 在眼表面产生和控制免疫反应。