MUCOSAL IMMUNITY AND INFECTION

粘膜免疫和感染

• 批准号: 6091719
• 负责人: Michael E. Lamm
• 金额: $ 92.07万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6091719
• 关键词: infection; microorganism immunology; mucosal immunity

OVERALL DESCRIPTION (Adapted from application): This Program Project Application is submitted by an interactive group of basic and clinical scientists who propose to continue to study the mucosal immune system inr elation to parasitic, bacterial and viral infections. The proposed research focuses on the broad areas of pathogenesis, prevention and therapy of important diseases caused by different classes of infectious agents that infect the gastrointestinal, genital and respiratory mucosae. Project 1 addresses Entamoeba histolytica and amoebiasis, a leading cause of parasitic death and morbidity worldwide. The specific studies focus on the galactose-inhabitable lectin, that mediates the binding of Entamoeba to the intestinal epithelium. The goal is to identify immunogenic subdomains of the lectin that can be used to develop an effective oral subunit vaccine. The second project is on Helicobacter pylori, the major cause of peptic ulcer disease. Based upon studies of pathogenesis and mechanisms of immune defense, a major goal is to develop prophylactic and therapeutic vaccines that do not elicit an untoward inflammatory immune defense, a major goal is to develop prophylactic and therapeutic vaccines that do not elicit an untoward inflammatory immune response. Project 3 investigates how mucosal IgA antibodies can counter HIV at epithelial surfaces that are the portals of entry for sexual transmission of this virus. Monoclonal IgA antibodies to HIV, both extracellular and intracellularly. The mechanisms of action of such protection will be studied. The results may further the design of an effective mucosal vaccine for this sexually transmitted disease. The fourth project investigates IgA nephropathy, the most common type of glomerulonephritis, that is associated clinically with respiratory infection The roles that normal and aberrant IgA glycosylation, virus-specific T cells and glomerular mesangial cells play in disease pathogenesis will be investigated in a post infection mouse model in nephritis-sensitive and nephritis-resistant strains. The four projects are supported by administrative and hybridoma cores. The insights to be gained from this PROGRAM Project may e broadly applicable since many infections involve mucous membranes, either as sites of infection or as portals of entry into the host.

总体描述(改编自申请)：本计划项目申请由一个由基础和临床科学家组成的互动小组提交，他们建议继续研究粘膜免疫系统与寄生虫、细菌和病毒感染的关系。拟议的研究集中在由感染胃肠道、生殖器和呼吸道粘膜的不同类别的感染剂引起的重要疾病的发病机制、预防和治疗的广泛领域。项目1针对的是溶解组织内阿米巴和阿米巴病，这是全世界寄生虫死亡和发病的主要原因。具体的研究集中在半乳糖可居住的凝集素，它介导内阿米巴与肠上皮的结合。目的是确定可用于开发有效的口服亚单位疫苗的凝集素的免疫原性亚域。第二个项目是关于幽门螺杆菌，这是消化性溃疡疾病的主要原因。基于对免疫防御机制和发病机制的研究，一个主要目标是开发不引起不良炎症免疫防御的预防性和治疗性疫苗，一个主要目标是研制不引起不良炎症免疫反应的预防性和治疗性疫苗。项目3调查粘膜IgA抗体如何在上皮表面对抗艾滋病毒，上皮表面是这种病毒通过性传播进入的门户。抗HIV的单抗，包括细胞外和细胞内。将研究这种保护的作用机制。这一结果可能会进一步设计出针对这种性传播疾病的有效粘膜疫苗。第四个项目研究临床上与呼吸道感染相关的最常见的肾小球肾炎--IgA肾病，将在肾炎敏感株和肾炎耐药株感染后的小鼠模型中研究正常和异常的IgA糖基化、病毒特异性T细胞和肾小球系膜细胞在疾病发病机制中的作用。这四个项目得到了行政和杂交瘤核心的支持。从该计划项目中获得的见解可能广泛适用，因为许多感染涉及粘膜，要么作为感染部位，要么作为进入宿主的入口。