ENDOCRINE CONTROL OF THE OCULAR SECRETORY IMMUNE SYSTEM

眼分泌免疫系统的内分泌控制

• 批准号: 3260812
• 负责人: David A. Sullivan
• 金额: $ 18.88万
• 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/3260812
• 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.

眼睛的分泌性免疫系统被设计成保护眼睛。 眼表抵抗微生物入侵。 这个系统通过 主要通过分泌型伊加（sIgA）抗体， 细菌定植，抑制病毒粘附，消除 寄生虫感染和阻断毒素诱导的粘膜损伤 上皮细胞 因此，sIgA可能发挥独特的和关键的作用， 在保护角膜完整性和防止严重的视力损害方面， 损伤和可能失明。 长期目标是 这项拨款申请是为了促进我们的理解， 神经内分泌系统调节分泌免疫系统 the eye. 实验程序涉及大鼠和小鼠模型， 细胞培养，流式细胞术，放射自显影，sIgA转运 研究，配体结合测定，免疫测定， 层析技术、免疫荧光和电子显微镜 显微镜，图像分析，免疫反应研究， 可溶性、颗粒性和病毒性抗原，自身免疫性疾病和 内分泌器官切除和重建研究。 具体目标 主要有：（1）确定激素和神经内分泌因素， 调节泪腺的免疫、结构和功能。 这些 研究包括（a）确定内分泌相互作用 控制分泌型细胞的表达、分泌和功能 组成部分（SC）在泪腺腺泡细胞在体外; SC是一个 表面防御的关键决定因素，并调节 泪液中伊加抗体的运输。 (b)评价 控制分泌免疫的神经内分泌相互关系 在体内的眼睛系统。 这些实验也将 确定激素和神经内分泌因子调节 泪腺形态和泪液产生。 (2)分析 神经内分泌对眼分泌免疫反应的影响 确定的可溶性、颗粒和病毒抗原。 (3)发展 改善或预防特异性自身免疫的内分泌策略 泪腺疾病。 这些研究的结果应该 阐明了神经系统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，本发明还提供了一种方法， 这些发现可能与眼睛的健康有关，因为它们（a） 探讨调节眼神经和内分泌机制 对抗原攻击的分泌性免疫应答;（B）检查a 可能的激素策略，以有效地治疗特定的自身免疫性 泪腺疾病和（c）评估激素和 调节泪腺结构和泪液的神经因子 生产