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的发病机制研究