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ANTERIOR CHAMBER INFLUENCE ON OCULAR ANTIGENS

前房对眼抗原的影响

基本信息

批准号：
2888176
负责人：
J WAYNE STREILEIN
金额：
$ 33.68万
依托单位：
SCHEPENS EYE RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-11-01 至 2000-06-30
项目状态：
已结题

项目摘要

Systemic immune responses to anterior chamber antigens are deviant in that certain types of immune effectors (delayed hypersensitivity and complement fixing antibodies) are selectively deleted and/or suppressed, whereas other effectors (cytotoxic T cells, non-complement fixing antibodies) are induced. This unique pattern of immune effectors has been termed Anterior Chamber Associate Immune Deviation (ACAID). Since it has been determined that anatomic integrity of he antigen-containing eye and the spleen is required for ACAID induction during the first 4-5 days after intracameral antigen injection of antigen, experiments have been designed to investigate the cellular and molecular bases of these requirements. Two related hypotheses will be tested experimentally: (1) A qualitatively and/or quantitatively distinct antigen-specific ACAID-inducing signal escapes into the blood from eyes into which antigen has been introduced; (2) In the spleen, the ACAID-inducing signal preferentially activates TH2 cells, which in turn impair the induction of TH1 cells that are responsible for the generation of delayed hypersensitivity and complement fixing antibodies. Recent evidence indicates that expression of immunity within the eye may also be abnormal. A third hypothesis to be tested is Local intraocular factors (cells and molecules) act to reduce intraocular expression of delayed hypersensitivity. Since alterations in induction and expression of immunity toward intraocular antigens exist, a fourth hypothesis to be tested states that Deviant immune responses (ACAID) may have beneficial or deleterious effect in the eye, leading to immune-related ocular disease. To test these hypotheses, we have devised four Specific Aims: 1. Study of the eye as a source of the ACAID-inducing signal. 2. Analyze splenic T cells to identify and study regulatory lymphocytes in ACAID. 3. Characterize immune effector cell responses in the anterior chamber of the eye. 4. Explore the possible relationships between ACAID and experimental ocular diseases. As new data accumulate concerning the unique relationship between the systemic immune system and the eye, progress should be possible in our understanding of the etiology of ocular disease in which the immune system plays an important pathogenic role. Based on this understanding, strategies can then be devised to manipulate the immune system in specific ways designed to prevent and/or treat immunopathogenic ocular diseases.

对前房抗原的全身免疫应答是异常的，某些类型的免疫效应物（迟发型超敏反应和补体固定抗体）被选择性地删除和/或抑制，而其他效应物（细胞毒性T细胞，非补体固定抗体）是诱导。这种独特的免疫效应物模式被称为前免疫效应物。灭菌室相关免疫偏离（ACAID）。既然已经确定含有抗原的眼睛和脾脏的解剖完整性前房内给药后前4-5天内ACAID诱导所需的抗原注射的抗原，实验已经被设计成调查这些需求的细胞和分子基础。两个相关假设将通过实验进行检验：（1）定性和/或定量不同的抗原特异性ACAID诱导信号逃逸到（2）在已引入抗原的眼睛的血液中; 在脾脏中，ACAID诱导信号优先激活TH 2细胞，反过来又削弱了TH 1细胞的诱导，TH 1细胞负责产生迟发型超敏反应和补体结合抗体。最近的证据表明，眼睛内的免疫表达可能也不正常。第三个待检验的假设是局部眼内因子（细胞和分子）起作用以减少迟发性超敏反应由于诱导和表达的改变，存在对眼内抗原的免疫，第四种假设是测试表明，异常免疫反应（ACAID）可能具有有益或在眼睛中的有害作用，导致免疫相关的眼部疾病。为了验证这些假设，我们设计了四个具体目标： 1. 研究眼睛作为ACAID诱导信号的来源。 2. 分析脾T细胞以鉴定和研究很好。 3. 表征前房中的免疫效应细胞反应， the eye. 4. 探索ACAID和实验之间的可能关系眼部疾病随着新数据的积累，全身免疫系统和眼睛，进展应该是可能的，在我们的了解眼部疾病的病因，其中免疫系统起重要致病作用。基于这一认识，然后可以设计策略来操纵免疫系统，设计用于预防和/或治疗免疫致病性眼病的方法。