GENETICS OF ANTIBODIES TO PERIODONTAL PATHOGENS

牙周病原体抗体的遗传学

• 批准号: 3220313
• 负责人: JEROME HABER
• 金额: $ 19.21万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3220313
• 关键词: Actinomyces; antibody formation; bacterial antigens; disease /disorder model; disease /disorder proneness /risk; gene expression; genetic models; genetic strain; immunogenetics; immunoglobulins; laboratory mouse; linkage mapping; oral bacteria; periodontium disorder; saliva; serum; surface antigens

Caries and periodontal diseases afflict most individuals at some time during life and are the major causes of tooth loss in all age groups. The factors which determine resistance or susceptibility to these diseases are unknown. These diseases are caused by dental plaque associated microorganisms, which colonize the tooth surface and gingival sulcus. The ability of these organisms to colonize the oral cavity depends upon their adherence to the tooth surface or other bacteria. Specialized cell surface structures mediate the adherence of bacteria to oral surfaces, and antibodies directed against these structures have been shown to inhibit bacterial adherence and colonization. An attractive explanation for differences in disease susceptibility is genetically controlled variations in the antibody response to adherence associated structures on periodontal pathogens. The proposed project, which is based on ongoing studies of genetic control of the serum antibody responses to Actinomyces viscosus, is a detailed study of genetic control of the specificity of serum antibodies to purified type 1 fimbriae (T-1) which mediate the adherence of Actinomyces viscosus strain T14V to saliva coated hydroxyapetite surfaces. Experiments will be done in inbred mice and isoelectric focusing and idiotype specific ELISA's will be used to determine the spectrotypes and idiotypes of anti-T1 antibodies. A strain survey will be done and appropriate parental strains will be selected for genetic analysis. The serum anti-T-1 antibody responses of the parental strains, F1 hybrid and backcross mice will be analyzed, as well as the responses of congenic and recombinant inbred mice. Segregation and linkage analyses of these data will substantiate the hypotheses that the specificity of serum antibodies to T-1 are genetically determined and provide insight into the nature of this control. Different, well characterized anti-T-1 sera will be tested in an in vitro adsorption inhibition assay to correlate the spectrotype and idiotype of anti- T1 antibodies with their ability to inhibit the adherence of A. viscosus strain T14V cells to an "in vitro tooth surface." These studies will hopefully provide an understanding of the role of genetics in determining disease susceptibility and determine the characterisitcs of protective anti-T-1 antibody responses. This information would be useful in the development of immunization protocols in humans to prevent or control periodontal diseases.

龋齿和牙周病折磨着大多数人， 是所有年龄段牙齿脱落的主要原因 组 决定抗性或易感性的因素 这些疾病是未知的。 这些疾病是由 牙菌斑相关的微生物，其在牙菌斑中定植， 牙齿表面和龈沟。 这些生物的能力 在口腔中定植取决于它们对 牙齿表面或其他细菌。 特化细胞表面 结构介导细菌对口腔表面的粘附， 针对这些结构的抗体已经显示 抑制细菌粘附和定植。 一个有吸引力 对疾病易感性差异的解释是遗传学上的 抗体对粘附反应的受控变化 牙周病原体的相关结构。 拟议 项目，该项目是基于正在进行的遗传控制研究， 对粘性放线菌的血清抗体应答，是一种 血清特异性的遗传控制的详细研究 针对纯化的1型菌毛（T-1）的抗体， 粘性放线菌T14 V菌株对唾液包被的粘附 羟基磷灰石表面。 实验将在近交系小鼠中进行 将使用等电聚焦和独特型特异性ELISA 以确定抗T1抗体的谱型和独特型。 将进行菌株调查， 进行基因分析。 血清抗T-1抗体 亲本品系、F1代杂交和回交小鼠的反应 将进行分析，以及同类和 重组近交系小鼠 分离和连锁分析 这些数据将证实以下假设： T-1的血清抗体是由遗传决定的， 深入了解这种控制的本质。 不一样 将在体外吸附试验中检测表征的抗T-1血清 抑制试验，以关联抗 T1抗体具有抑制A. 粘性菌株T14 V细胞粘附于“体外牙齿表面”。“这些 研究将有希望提供一个了解的作用， 遗传学在确定疾病易感性和确定 保护性抗T-1抗体应答的特征。 这 信息将有助于免疫发展 在人类中预防或控制牙周病的方案。