MUCOSAL IMMUNITY AND INFECTION

总体描述（改编自申请）：本计划项目申请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对寄生虫，细菌和病毒感染的影响。拟议的研究重点是广泛的发病机制，预防和治疗由感染胃肠道，生殖器和呼吸道粘膜的不同类别的传染性病原体引起的重要疾病。项目1涉及溶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抑制凝集素，介导的结合内阿米巴肠上皮细胞。目标是鉴定凝集素的免疫原性亚结构域，其可用于开发有效的口服亚单位疫苗。第二个项目是关于幽门螺杆菌，这是消化性溃疡的主要原因。基于对免疫防御的发病机理和机制的研究，一个主要目标是开发不引起不利的炎性免疫防御的预防性和治疗性疫苗，一个主要目标是开发不引起不利的炎性免疫应答的预防性和治疗性疫苗。项目3研究粘膜IgA抗体如何在上皮表面对抗HIV，上皮表面是这种病毒通过性传播的入口。抗HIV单克隆IgA抗体，细胞外和细胞内。将研究这种保护的作用机制。这些结果可能进一步设计一种有效的粘膜疫苗用于这种性传播疾病。第四个项目研究IgA肾病，最常见的类型的肾小球肾炎，这是临床上与呼吸道感染有关的正常和异常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发挥的作用将在感染后的小鼠模型中在肾炎敏感和肾炎抗性菌株中进行研究。这四个项目得到了行政和杂交瘤核心的支持。由于许多感染都涉及粘膜，无论是作为感染部位还是作为进入宿主的门户，因此从本研究项目中获得的见解可能具有广泛的适用性。

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.