AUTOIMMUNE GASTRITIS INITIATED BY HELICOBACTER INFECTION

描述（摘自研究者摘要） 幽门螺杆菌是一种主要的病原体， 感染了世界上一半以上的人口，与胃和 十二指肠溃疡疾病、粘膜相关淋巴瘤和腺癌。 幽门螺杆菌感染最初导致募集和激活 非特异性先天免疫反应。 这些单核细胞分泌 直接影响胃上皮的促炎细胞因子，以及 将淋巴细胞募集到炎症病灶。 知之甚少 关于这种免疫渗透的特征，它的抗原特异性， 或其在随后的胃病发展中的作用;然而， 研究表明，幽门螺杆菌感染可导致抗- 壁细胞抗体。 这导致了一种假设， 感染诱导自身免疫反应， 上皮细胞破坏和病理学。 一种小动物模型， 幽门螺杆菌感染，猫幽门螺杆菌小鼠模型， 疾病，并允许仔细分析适应性免疫反应， 螺杆菌感染。 研究人员已经证明，它是宿主T细胞 这种反应对于猫血吸虫相关胃肠道疾病的发展至关重要。 病理 这引起了人们对细胞免疫的作用的关注， 反应，及其潜在的自身免疫性，在发展中， 幽门螺杆菌相关的胃上皮细胞破坏和病理学。 这份补助金申请的重点是了解 幽门螺杆菌感染的细胞免疫反应，以及 随后胃上皮改变。 这些上皮细胞的变化 增殖、分化和细胞死亡导致临床溃疡病 以及组织化生增多 为了阐明这种免疫/上皮细胞 关系及其后遗症，研究人员建议确定 免疫T淋巴细胞亚群对幽门螺杆菌的发展至关重要- 相关的胃病理学，并确定其机制， 幽门螺杆菌诱导的免疫应答产生胃上皮病理学。 了解宿主免疫应答的基本机制， 幽门螺杆菌诱导胃上皮病变将为 进一步研究炎症反应的调节和设计 幽门螺杆菌感染及相关消化道疾病的免疫治疗 疾病

DESCRIPTION (Taken from the Investigator's Abstract) The bacteria, Helicobacter pylori, is a major pathogen which, in addition to infecting over half of the world's population, is linked to gastric and duodenal ulcer disease, mucosal-associated lymphomas, and adenocarcinoma. Infection with H.pylori initially leads to recruitment and activation of the non-specific innate immune response. These mononuclear cells secrete proinflammatory cytokines that directly affect the gastric epithelium, as well as recruit lymphocytes into the inflammatory focus. Very little is known about the characteristics of this immune infiltrate, its antigen specificity, or its role in subsequent development of gastric diseases; however, it has now been shown that infection with H.pylori can lead to the production of anti- parietal cell antibodies. This has led to the hypothesis that Helicobacter infection induces an autoimmune response that causes subsequent gastric epithelial cell destruction and pathology. A small animal model of Helicobacter infection, the H.felis mouse model, closely mimics the human disease and allows a careful analysis of the adaptive immune response to Helicobacter infection. The investigator has shown that it is the host T cell response that is crucial for the development of H.felis-associated gastric pathology. This has directed attention to the role of the cellular immune response, and its potential autoimmune nature, in the development of Helicobacter-associated gastric epithelial cell destruction and pathology. This grant application focuses on understanding the relationship between the cellular immune response to Helicobacter infection, and the development of subsequent gastric epithelial alterations. These changes in epithelial proliferation, differentiation, and cell death lead to clinical ulcer disease and increased metaplasia. In order to elucidate this immune/epithelial cell relationship and its sequelae, the investigators propose to identify the immune T lymphocyte subset critical for the development of Helicobacter- associated gastric pathology and to determine the mechanism by which Helicobacter-induced immune responses generate gastric epithelial pathology. The understanding of the basic mechanisms by which the host immune response to Helicobacter induces gastric epithelial pathology will lay the foundation for further studies on the regulation of the inflammatory response and the design of immunotherapies for Helicobacter infection and associated digestive diseases.