LEWIS ANTIGEN EXPRESSION AND PATHOGENESIS OF H PYORI

幽门螺杆菌是一种革兰氏阴性细菌，生活在 胃壁衬里的粘液层是慢性胃炎的主要原因 胃炎和消化性溃疡，这是一个主要的危险因素 胃癌。幽门螺杆菌重要性的新认识 作为一种人类病原体，这种传染病引起了人们的关注： 现在已经很好地确定了感染应该是 根除，而不仅仅是症状得到治疗。由以下成分组成的疫苗 完整的螺杆菌(全细胞超声酸盐或热致死细菌) 已经证明单独或与细菌毒素佐剂联合使用 在几种动物感染模型中提供免疫力。一大专业 这种方法的问题是，幽门螺杆菌的固有因素可能 引起炎症和不适当的免疫反应。这样的一个 因子是脂多糖(LPS)，它是已知的中介 炎症和诱导细胞因子的释放。宾语的结构 幽门螺杆菌脂多糖的多糖部分最近被阐明 对于三种不同的菌株；每一种都被发现是唯一的，并且 以Lewis x和/或Lewis y血型抗原终止。幽门螺杆菌是 第一个被发现表达这些Lewis抗原决定簇的细菌。 Lewis x和Lewis在正常胃组织中均有发现，但 在某些肿瘤细胞中大量存在。关于H。 幽门螺杆菌感染期间携带的幽门螺杆菌血型抗原可能是 考虑过了。它们可以(1)作为分子模拟物，使宿主失明 幽门螺杆菌，从而帮助这种病原体逃避免疫 系统；(2)作为粘附素与细胞上的受体相互作用 胃粘膜；(3)刺激引起组织的自身免疫反应 损害，从而导致疾病状态；或(4)引起口服 因此导致寄主清除能力下降 也有刘易斯抗原标记的肿瘤。你们谁也不是 假设是相互排斥的，它们中的任何一个都不会失败 会对宿主造成损害。这位新的H。 幽门螺杆菌研究计划是确定刘易斯抗原在 这种细菌的致病机制和致癌潜力。 具体地说，基于Lewis抗原的幽门螺杆菌血清分型系统 将建立对不同临床菌株的分型表达 消息来源。此外，幽门螺杆菌菌株在生产 将构建Lewis抗原并对其致病作用进行评估 属性及其作为候选疫苗的潜力。

Helicobacter pylori is a gram-negative bacterium that lives in the mucus layer of the stomach lining and is the major cause of chronic gastritis and peptic ulcer disease, which is a major risk factor for gastric cancer. The recent realization of the importance of H. pylori as a human pathogen has focused attention on this infectious disease: It is now well established that it is the infection that should be eradicated, not just the symptoms treated. Vaccines composed of whole Helicobacter (either whole-cell sonicates or heat-killed bacterial) alone or in combination with bacterial toxin adjuvant have been shown to provide immunity in several animal models of infection. One major problem with this approach is that factors inherent in H. pylori may cause inflammation and an inappropriate immune response. One such factor is lipopolysaccharide (LPS), which is known to mediate inflammation and induce cytokine release. The structure of the O polysaccharide portion of H. pylori LPS has recently been elucidated for three different strains; each was found to be unique and to terminate in Lewis x and/or Lewis y blood group antigens. H. pylori is the first bacterium found to express these Lewis antigen determinants. Lewis x and Lewis are found on normal gastric tissue but are more abundant on certain tumor cells. Several hypotheses for the role of H. pylori-borne blood group antigens during H. pylori infection can be considered. They may (1) serve as molecular mimics, blinding the host to H. pylori and thereby helping this pathogen to evade the immune system; (2) act as adhesins interacting with cellular receptors on the gastric mucosa; (3) stimulate autoimmune reactions that cause tissue damage and thus contribute to the disease state; or (4) elicit oral tolerance and thus lead to a decreased ability of the host to clear tumors that are also marked by Lewis antigens. None of thee hypotheses is mutually exclusive, nor would any of them fail to contribute to damage to the host. The long-term goal of this new H. pylori research program is to determine the role of Lewis antigens in the pathogenesis and carcinogenic potential of this bacterium. Specifically, a serotyping system for H. pylori based on Lewis antigen expression will be established to type strains from various clinical sources. In addition, H. pylori strains efficient in the production of Lewis antigens will be constructed and evaluated for their pathogenic attributes and their potential as vaccine candidates.