Ocular Mucosal Immunity

眼粘膜免疫

• 批准号: 7250145
• 负责人: ANTHONY BART NESBURN
• 金额: $ 37.02万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7250145
• 关键词: Address; Adjuvant; Anatomy; Antibodies; Antigen Presentation; Antigen-Presenting Cells; Antigens; Appendix; Area; CD4 Positive T Lymphocytes; CD44 gene; CD8B1 gene; Calculi; Cells; Cellular Immunity; Corneal Diseases; Distal; Dose; Epitopes; Eye; Eye Infections; Eyedrops; Glycoproteins; Goals; Grant; Herpesvirus 1; Histology; Human; Human herpesvirus 1 glycoprotein D; Immune; Immune Tolerance; Immune response; Immune system; Immunity; Immunization; Immunobiology; Immunoglobulin G; Individual; Infection; Inflammation; Lacrimal gland structure; Lymphoid Tissue; Mediating; Modeling; Mucosal Immune Responses; Mucosal Immunity; Mucous Membrane; Mus; National Eye Institute; Nose; Oryctolagus cuniculus; Peptides; Phenotype; Play; Population; Production; Recurrence; Relative (related person); Research; Research Personnel; Role; Serum; Simplexvirus; Study models; Surface; System; T-Cell Activation; T-Lymphocyte; Techniques; Technology; Testing; Therapeutic; Time; Topical application; Transcriptional Activation; Up-Regulation; Vagina; Work; base; conjunctiva; cytokine; immunogenic; immunogenicity; lymph nodes; man; new technology; novel; novel strategies; pathogen; programs; prophylactic; research study; response; subcutaneous

DESCRIPTION (provided by applicant): The overall goal of this proposal is to develop a better understanding of the Ocular Mucosal Immune System (OMIS). The OMIS is the immune barrier that protects the eye from infection. This will be done in an experimental rabbit model whose ocular anatomy; immuno-histology and immune response to HSV infection mimics that of man. Our previous work has shown in rabbits mucosal ocular protection against HSV-1 was mediated by local mucosal, but not systemic immunization with HSV glycoprotein D (gD) and strong adjuvant. The mucosal protection in this model is due to cell-mediated immunity rather than secreted (slgA) or serum (IgG) antibodies. Using recently developed technologies, protective immunogenic HSV-1 gD peptide epitopes will be used to investigate the mechanism of ocular mucosal immunity and protection. These test peptides, formulated with novel, "safe" highly effective mucosal adjuvants will be administered topically to the eye to induce maximal local OMIS immunity. This research will be performed in these Specific Aims: Aim 1. Test the hypothesis that HSV-1 gD peptide epitopes found to stimulate the mouse mucosal immune system will also stimulate the rabbit OMIS and protect the eye against HSV challenge; Aim 2 -- Test the hypothesis that topical ocular delivery of the best protective gD peptides identified Aim 1 will activate Th1 immune responses in the OMIS. Aim 3A--Test the hypothesis that Nasal Associated Lymphoid Tissue (NALT) immunization is essential for OMIS responses and ocular protection and investigate whether the OMIS is part of the common mucosal immune system after topical delivery of gD peptides identified in Aim 1; and Aim 3B--Using high doses of our test antigens and the isolated NALT experimental system, we will test the hypothesis that NALT is necessary for induction of OMIS tolerance and, inversely, whether OMIS is involved in NALT tolerance. This research will provide important new information regarding the immunological composition and function of OMIS and explore means of inducing ocular mucosal immune protection and tolerance. It will test new technologies, new approaches in antigen presentation and mucosl adjuvants that could be stepping-stones to developing efficient ocular immunoprotective therapies. This addresses the NEI's Corneal Diseases Program objectives to "Further study of the mechanisms of mucosal immunity".

描述（由申请人提供）：该提案的总体目标是更好地了解眼粘膜免疫系统（OMIS）。 OMIS 是保护眼睛免受感染的免疫屏障。这将在实验兔子模型中完成，该模型的眼部解剖结构如下：免疫组织学和对 HSV 感染的免疫反应与人类相似。 我们之前的工作表明，针对 HSV-1 的兔子粘膜眼部保护作用是通过局部粘膜介导的，而不是用 HSV 糖蛋白 D (gD) 和强佐剂进行全身免疫介导的。该模型中的粘膜保护是由于细胞介导的免疫而不是分泌的 (slgA) 或血清 (IgG) 抗体。利用最近开发的技术，保护性免疫原性HSV-1 gD肽表位将用于研究眼粘膜免疫和保护机制。这些测试肽采用新型、“安全”高效粘膜佐剂配制而成，将局部施用于眼睛，以诱导最大程度的局部 OMIS 免疫力。这项研究将在以下具体目标中进行： 目标 1. 测试以下假设：刺激小鼠粘膜免疫系统的 HSV-1 gD 肽表位也将刺激兔子 OMIS 并保护眼睛免受 HSV 攻击；目标 2——测试目标 1 确定的最佳保护性 gD 肽的局部眼部递送将激活 OMIS 中的 Th1 免疫反应的假设。目标 3A——检验鼻相关淋巴组织 (NALT) 免疫对于 OMIS 反应和眼部保护至关重要的假设，并研究在局部递送目标 1 中确定的 gD 肽后 OMIS 是否是常见粘膜免疫系统的一部分；目标 3B——使用高剂量的测试抗原和分离的 NALT 实验系统，我们将测试 NALT 对于诱导 OMIS 耐受所必需的假设，以及反过来，OMIS 是否参与 NALT 耐受。 这项研究将为OMIS的免疫组成和功能提供重要的新信息，并探索诱导眼粘膜免疫保护和耐受的方法。它将测试新技术、抗原呈递和粘膜佐剂的新方法，这些可能成为开发有效的眼部免疫保护疗法的垫脚石。这解决了 NEI 角膜疾病计划的目标，即“进一步研究粘膜免疫机制”。