BIOLOGY, IMMUNOLOGY & THERAPY OF ACANTHAMOEBA KERATITIS

生物学、免疫学

• 批准号: 2711074
• 负责人: HASSAN ALIZADEH
• 金额: $ 23.77万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2711074
• 关键词: Acanthamoeba; Langerhans' cell; T lymphocyte; cornea disorder; delayed hypersensitivity; disease /disorder prevention /control; enzyme linked immunosorbent assay; eye disorder chemotherapy; fluorescence microscopy; hamsters; humoral immunity; immunization; immunoglobulin A; immunotherapy; interleukin 1; intracellular parasitism; keratitis; lymphokines; mucosal immunity; oral administration; organ culture; parasitic eye infections; protozoal antigen

Acanthamoeba keratitis is a sight-threatening disease that is caused by Invasion of the eye by a free-living amoeba of the genus Acanthamoeba. Since its initial description in 1973, the incidence of Acanthamoeba keratitis has steadily increased. In spite of significant improvement in the diagnosis of Acanthamoeba keratitis, progress in developing and utilizing effective antimicrobial agents for treating this disease have been disappointing. Moreover, the emergence of drug resistance poses a serious problem in the management of Acanthamoeba infections. The long range goal of the present project is to develop effective strategies for preventing and treating Acanthamoeba keratitis. A growing body of evidence suggests that the mammalian immune system, if properly activated, is capable of preventing and controlling ocular Acanthamoeba infections as well as infections produced by other microorganisms. Therefore, a secondary and equally Important, long range goal of this project is to gain a better understanding of the immune effector mechanisms that protect the cornea from infectious agents. In order to develop effective immunotherapeutic modalities, it is necessary to fully characterize and evaluate the immunobiology of Acanthamoeba keratitis. The present application seeks to characterize and evaluate the immunobiology of experimental Acanthamoeba keratitis in a Chinese hamster model of this disease. Three specific aims will be addressed. The first specific aim will characterize the protective immunity to Acanthamoeba keratitis that is induced by oral and topical administration of Acanthamoeba antigens. The second specific aim will characterize the systemic and local ocular immune responses that are induced by corneal infections in Chinese hamsters. Preliminary studies indicate that the presence of Langerhans cells in corneas exposed to Acanthamoeba-laden contact lenses prevents the development of Acanthamoeba keratitis. Therefore, the third specific aim will evaluate the role of corneal Langerhans cells in the resistance to Acanthamoeba keratitis.

阿米巴角膜炎是一种威胁视力的疾病， 由自由生活的阿米巴属的阿米巴侵入眼睛。 自1973年首次描述以来，阿米巴的发病率 角膜炎一直在增加。 尽管有了显著改善， 在阿米巴角膜炎的诊断中， 利用有效的抗微生物剂治疗这种疾病， 令人失望 此外，耐药性的出现也构成了一个 阿米巴感染管理中的严重问题。长 本项目的范围目标是制定有效的战略， 防治阿米巴角膜炎。 越来越多的 有证据表明哺乳动物的免疫系统， 激活，能够预防和控制眼部阿米巴原虫 感染以及由其他微生物产生的感染。 因此，一个次要的，同样重要的，长期的目标， 该项目旨在更好地了解免疫效应器 保护角膜免受感染的机制。为了 开发有效的免疫模式，有必要充分 描述和评价阿米巴角膜炎的免疫生物学。 本申请寻求表征和评估本发明的组合物。 实验性阿米巴角膜炎免疫生物学研究 这种疾病的模式。将讨论三个具体目标。 第一个具体目标将描述保护性免疫力的特征， 口服和局部给药引起的阿米巴角膜炎 阿米巴抗原。 第二个具体目标将描述 由角膜炎诱导的全身和局部眼部免疫应答 中国仓鼠感染。 初步研究表明， 暴露于载有阿米巴的角膜中存在朗格汉斯细胞 隐形眼镜可防止阿米巴角膜炎的发展。 因此，第三个具体目标将评估角膜的作用， 朗格汉斯细胞在抗阿米巴角膜炎中的作用。