ENDOCRINE CONTROL OF THE OCULAR SECRETORY IMMUNE SYSTEM

眼分泌免疫系统的内分泌控制

• 批准号: 3260811
• 负责人: David A. Sullivan
• 金额: $ 17.52万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1993-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3260811
• 关键词: Sjogren's syndrome; androgens; autoimmune disorder; autoradiography; bactericidal immunity; chromatography; disease /disorder prevention /control; electron microscopy; electrophoresis; hormone regulation /control mechanism; immunity; immunocytochemistry; immunofluorescence technique; immunoglobulin A; immunologic techniques; immunopathology; laboratory mouse; laboratory rat; lacrimal apparatus; lacrimal disorder; lymphokines; neuroendocrine system; neuropeptides; radioassay; radioimmunoassay; secretory immune system; tear; tissue /cell culture; virus antigen

The secretory immune system of the eye is designed to protect the ocular surface against microbial invasion. This system, by acting primarily through secretory IgA (sIgA) antibodies, prevents bacterial colonization, inhibits viral adhesion, abolishes parasitic infestation and blocks toxin-induced damage in mucosal epithelial cells. Thus, sIgA may play a unique and crucial role in preserving corneal integrity and defending against severe visual impairment and possible blindness. The long-range objective of this grant application is to advance our understanding of how the neural-endocrine system regulates the secretory immune system of the eye. Experimental procedures involve rat and mouse models, cell cultures, flow cytometry, autoradiography, sIgA transport studies, ligand binding determinations, immunoassays, chromatographic techniques, immunofluorescence and electron microscopy, image analysis, immune response studies with defined soluble, particulate and viral antigens, autoimmune disorders and endocrine organ ablation and reconstitution studies. Specific aims are: (1) To identify the hormonal and neuroendocrine factors that regulate lacrimal gland immunity, structure and function. These studies include (a) determination of the endocrine interactions controlling the expression, secretion and function of secretory component (SC) in lacrimal gland acinar cells in vitro; SC is a critical determinant for surface defense and modulates the transport of IgA antibodies in tears. (b) evaluation of the neural-endocrine interrelationships governing the secretory immune system of the eye in vivo. These latter experiments will also identify the hormonal and neuroendocrine factors regulating lacrimal gland morphology and tear production. (2) To analyze the neural-endocrine impact on the ocular secretory immune response to defined soluble, particulate and viral antigens. (3) To develop an endocrine strategy to ameliorate or prevent specific autoimmune disorders of the lacrimal gland. Results from these studies should clarify the extensive and complex interactions between the neural, endocrine and immune systems in the lacrimal gland. In addition, findings may have health relatedness for the eye, because they (a) explore the neural and endocrine mechanisms regulating the ocular secretory immune response to antigenic challenge; (b) examine a possible hormonal strategy to effectively treat specific autoimmune disorders of the lacrimal gland and (c) evaluate hormonal and neural factors that modulate lacrimal gland structure and tear production.

眼睛的分泌免疫系统旨在保护 眼表防止微生物入侵。这个系统，通过采取行动 主要通过分泌型IgA(SIgA)抗体，防止 细菌定植，抑制病毒黏附，废除 寄生侵染和阻断毒素引起的粘膜损伤 上皮细胞。因此，SIgA可能会扮演一个独特而关键的角色 在保护角膜完整性和抵御严重视力方面 损伤和可能的失明。的长远目标 这项拨款申请是为了加深我们对 神经内分泌系统对小鼠的分泌性免疫系统的调节作用 眼睛。实验程序包括大鼠和小鼠模型， 细胞培养、流式细胞术、放射自显影、SIgA转运 研究，配基结合测定，免疫分析， 层析技术、免疫荧光和电子 显微镜、图像分析、免疫反应研究 可溶性、颗粒性和病毒抗原、自身免疫性疾病和 内分泌器官消融和重建研究。具体目标 是：(1)确定激素和神经内分泌因素 调节泪腺免疫、结构和功能。这些 研究包括：(A)内分泌相互作用的测定 控制分泌物的表达、分泌和功能 泪腺腺泡细胞的成分(SC)；SC是一种 地面防御的关键决定因素，并调节 泪水中的IgA抗体的运输。(B)评估 支配分泌性免疫的神经-内分泌相互关系 活体中的眼睛系统。后面的这些实验也将 确定调节激素和神经内分泌的因素 泪腺形态和泪液生成。(2)分析 神经内分泌对眼部分泌性免疫反应的影响 定义了可溶性、颗粒和病毒抗原。(三)大力发展 改善或预防特定自身免疫的内分泌策略 泪腺紊乱。这些研究的结果应该是 阐明神经之间广泛而复杂的相互作用， 泪腺的内分泌和免疫系统。此外, 这些发现可能与眼睛的健康有关，因为它们(A) 探索眼部神经和内分泌调节机制 对抗原攻击的分泌性免疫反应；(B)检查a 有效治疗特定自身免疫的可能激素策略 泪腺疾病和(C)评估激素和 调节泪腺结构和泪液的神经因素 制作。