MUCOSAL IMMUNOLOGY OF HELICOBACTER-INDUCED GASTRITIS

螺杆菌引起的胃炎的粘膜免疫学

• 批准号: 2145685
• 负责人: STEVEN J CZINN
• 金额: $ 16.58万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-15 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2145685
• 关键词: Helicobacter; active immunization; antibacterial antibody; bacterial antigens; bacterial vaccines; cellular immunity; enzyme linked immunosorbent assay; gastritis; gastrointestinal infection; germ free condition; humoral immunity; immunocytochemistry; immunoprecipitation; laboratory mouse; microorganism immunology; monoclonal antibody; oral administration; passive immunization

Helicobacter pylori (H. Pylori) is a gram-negative spiral organism which is found overlying the gastric epithelium in approximately 50% of adults in this country. We and others have confirmed a causal relationship between H. pylori infection and gastritis and peptic ulcer disease. Recently this infection has been implicated in the pathogenesis of gastric cancer. Although in-vitro studies indicate H. pylori is sensitive to most antimicrobial agents, numerous studies including our own have demonstrated the difficulty in consistently eradicating H. pylori from the gastric epithelium. Therefore, prevention of infections by oral immunization is an alternative approach for control of disease. Among several existing animal models for H. pylori-associated gastritis, a germ-free mouse model in our laboratory. Our preliminary results have shown that an oral vaccine containing Helicobacter antigens results in significantly elevated levels of anti-Helicobacter IgA antibodies in gastric secretions thereby conferring protection from infection. We have also shown that passive administration of anti-Helicobacter antibody can also prevent acute Helicobacter infection. There are a number of unanswered questions, however, which are the focus of this proposal. We seek to optimize our oral vaccine protocol for induction of protection from Helicobacter infection. A second area of concern is the possibility that the anti-Helicobacter immune response in addition to preventing infection could also play a role in the development of the gastric inflammation associated with Helicobacter infection. We plan a series of experiments to investigate this. Gastric tissue from immunized, and infected animals will be assessed for the presence of gastritis and immunophenotype for the presence of T cell subsets. Passive transfer of antibodies from infected or immunized mice into naive animals will allow us to determine if antibodies contribute to the pathogenesis of gastritis. If we are able to demonstrate infection, we will attempt to distinguish the disease producing antigens from protective ones. These studies may ultimately allow us to develop a safe efficacious subunit vaccine to prevent the morbidity and potential long-term consequences of Helicobacter infection.

幽门螺杆菌（H. Pylori）是一种革兰氏阴性螺旋生物， 在大约50％的成年人中发现胃上皮上覆盖 在这个国家。 我们和其他人已经确认了因果关系 幽门螺杆菌感染与胃炎和消化性溃疡疾病之间。 最近，这种感染与 胃癌。 尽管体外研究表明幽门螺杆菌是 对大多数抗菌剂敏感，包括我们的许多研究 自己表明了始终消除H的困难。 胃上皮的幽门螺杆菌。 因此，预防感染 通过口服免疫是控制疾病的另一种方法。 在几种现有的幽门螺杆菌相关胃炎的动物模型中， 我们实验室中的无菌小鼠模型。 我们的初步结果 表明，含有螺旋杆菌抗原的口服疫苗导致 抗螺杆杆菌IgA抗体的水平显着升高 胃分泌物，从而提供免受感染的保护。 我们有 还表明被动施用抗螺杆抗体可以 还可以防止急性旋转杆菌感染。 有很多 但是，未解决的问题是该提议的重点。 我们 寻求优化我们的口服疫苗协议以诱导保护 从旋翼杆菌感染中。 关注的第二个领域是可能性 除了防止 感染也可能在胃的发展中发挥作用 炎症与螺旋杆菌感染相关。 我们计划一个系列 实验以调查这一点。 免疫的胃组织， 将评估感染动物的胃炎和 T细胞亚群存在的免疫表型。 被动转移 受感染或免疫小鼠的抗体进入幼稚动物将允许 我们确定抗体是否有助于 胃炎。 如果我们能够证明感染，我们将尝试 区分产生抗原与保护性抗原的疾病。 这些 研究最终可能使我们能够开发一个安全的有效亚基 疫苗防止发病率和潜在的长期后果 螺旋杆菌感染。