IMMUNOBIOLOGY OF CAMPYLOBACTER JEJUNI

空肠弯曲菌的免疫生物学

• 批准号: 3136804
• 负责人: IRVING NACHAMKIN
• 金额: $ 15.38万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3136804
• 关键词: antibacterial antibody; antigens; bacterial antigens; bacterial proteins; bactericidal immunity; binding proteins; biochemistry; cell adhesion; chemical structure function; flagellin; gastroenteritis; gastrointestinal infection; gel electrophoresis; hamsters; high performance liquid chromatography; human tissue; immunization; immunochemistry; intestinal mucosa; laboratory mouse; microorganism immunology; peptide chemical synthesis; protein sequence; serology /serodiagnosis; synthetic peptide; tissue /cell culture; virulence

Studies on the pathogenesis of cholera and salmonella infections suggest that bacterial flagella may be more important than just serving as structures of motility. Campylobacter flagellin, the major protein of the flagella filament, is the major immunodominant protein of Campylobacter jejuni in patients will campylobacter enteritis. The role of campylobacter flagellin in the pathogenesis of campylobacter infection is unclear, however, recent studies suggest that the flagellin may possess an adhesin that could play a role in the interaction with the intestinal mucosa. Epidemiologic and limited volunteer challenge studies show that there is immunity after infection suggesting that some component of C. jejuni, and perhaps flagellin, may be useful for immunoprotection. The specific goals of this proposal are to define biochemically and immunologically some of the antigenic epitopes of campylobacter flagellin and to characterize biologically the nature of antibodies to these determinants. We will study the structure of antigenic epitopes by chemical and enzymatic degradation and immunoblot analysis. We will determine the composition, amino acid sequence (s), and lability of these epitopes by chemical and enzymatic methods to determine the minimal structural requirements for antigenic activity. We will synthesize these epitopes using solid- phase peptide synthesis to further characterize these epitopes and for use in characterizing the human antibody response. The function of flagellin epitopes will be studied by preparing labeled synthetic peptides and assessing the role of these epitopes as adhesins. Finally, we will assess the biological significance of human antibodies directed against these epitopes (i.e. immobilizing activity, bactericidal, inhibition of adherence) by isolating specific antibody through the use of immunoabsorbent columns prepared with synthetic peptides. This information should lead to a tetter understanding of the role of flagellin during infection and may suggest strategies for immunoprotection.

霍乱和沙门氏菌感染发病机制的研究 表明细菌鞭毛可能比仅仅更重要 作为运动结构。 弯曲杆菌鞭毛蛋白 鞭毛丝的主要蛋白质，是主要的免疫优势蛋白 患者体内的空肠弯曲菌蛋白 肠炎。 弯曲杆菌鞭毛蛋白在发病机制中的作用 弯曲杆菌感染的原因尚不清楚，但最近的研究 表明鞭毛蛋白可能具有可以发挥作用的粘附素 与肠粘膜相互作用的作用。 流行病学和有限的志愿者挑战研究表明 感染后存在免疫力，表明某些成分 空肠弯曲菌，也许还有鞭毛蛋白，可能有助于 免疫保护。 该提案的具体目标是从生化和 免疫学上弯曲杆菌的一些抗原表位 鞭毛蛋白并从生物学角度表征抗体的性质 对于这些决定因素。 我们将研究抗原的结构 通过化学和酶降解和免疫印迹确定表位 分析。 我们将确定组成、氨基酸序列 (s)，以及这些表位通过化学和酶促的不稳定性 确定最低结构要求的方法 抗原活性。 我们将使用固体合成这些表位 阶段肽合成以进一步表征这些表位和 用于表征人类抗体反应。 这 将通过制备标记的标记来研究鞭毛蛋白表位的功能 合成肽并评估这些表位的作用 粘附素。 最后，我们将评估其生物学意义 针对这些表位的人类抗体（即固定 活性、杀菌、抑制粘附）通过分离 通过使用免疫吸收柱获得特异性抗体 用合成肽制备。 这些信息应该导致 对鞭毛蛋白在感染过程中的作用有了更深入的了解 并可能提出免疫保护策略。