GENETICS OF ANTIBODIES TO PERIODONTAL PATHOGENS

牙周病原体抗体的遗传学

• 批准号: 3220311
• 负责人: JEROME HABER
• 金额: $ 13.77万
• 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 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3220311
• 关键词: Actinomyces; antibody formation; bacterial antigens; disease /disorder model; disease /disorder proneness /risk; gene expression; genetic models; genetic strain; immunogenetics; immunoglobulins; linkage mapping; oral bacteria; periodontium disorder; preventive dentistry; radioimmunoassay; radiotracer; saliva; serum; surface antigens; tooth

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 previous studies of genetic control of serum and salivary antibody responses to SRBC, is a detailed study of genetic control of serum and salivary antibody responses to a purified protein antigen (T-1) which mediates the adhrerence of Actinomyces viscosus strain T14V to saliva coated hydroxyapetite surfaces. Experiments will be done in inbred mice and a radioimmunoassay will be used to measure Ig isotype specific and responses to T-1 and A. viscosus strain T14V. A strain survey will be done and appropriate parental strains will be selected for genetic analysis. The serum and salivary 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 analysis of these data will substantiate the hypothesis that serum and salivary antibody responses to T-1 are genetically determined and provide insight into the nature of this control. Different, well characterized anti-T-1 sera and salivas will be tested in an in vivo adsorption inhibition assay to correlate magnitude and isotype of the anti-T1 response with the ability to inhibit the adhrence of A. viscosus strain T14V cells to an "in intro tooth surface." These studies will hopefully provide an understanding of the role of genetics in determining disease susceptibility and determine the characteristics 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.

龋齿和牙周病有时会困扰大多数人。 而且在所有年龄段都是牙齿脱落的主要原因。这个 决定对这些疾病的抗性或易感性的因素是 未知。这些疾病是由与牙菌斑相关的 微生物，它们定植在牙齿表面和牙龈沟中。这个 这些生物在口腔中定植的能力取决于它们的 附着在牙齿表面或其他细菌上。特化细胞表面 结构调节细菌在口腔表面的黏附，以及 针对这些结构的抗体已被证明能够抑制 细菌黏附和定植。一个吸引人的解释 疾病易感性的差异是由基因控制的变异 在对牙周黏附相关结构的抗体反应中 病原体。拟议的项目是基于以前的研究 SRBC的血清和唾液抗体反应的遗传控制是一种 血清和唾液抗体反应的遗传控制详细研究 T-1的纯化的蛋白抗原(T-1)，它介导了 粘性放线菌菌株T14V对唾液包被羟基磷灰石表面。 实验将在近亲交配的小鼠身上进行，并将使用放射免疫分析 检测免疫球蛋白同型特异性及对T-1和粘性支原体的反应 T14V。将进行菌株调查，适当的亲本菌株将 被选中进行遗传分析。血清和唾液中抗T-1抗体 亲本品系、F1杂交和回交小鼠的反应将是 分析了同源自交系和重组自交系的反应 老鼠。对这些数据的分离和连锁分析将证实 假设血清和唾液抗体对T-1的反应是 基因决定的，并提供了对这一本质的洞察 控制力。不同的，具有良好特性的抗T-1血清和唾液将是 在体内吸附抑制试验中测试，以关联大小和 具有抑制黏附能力的抗T1反应的同型 粘性支原体将T14V细胞株扩增到“内牙面”。这些 研究将有望提供对遗传学在疾病中的作用的理解。 确定疾病易感性并确定其特征 保护性抗T-1抗体反应。这些信息将是有用的 在人类免疫方案的开发中，以防止或 控制牙周病。