PROTECTIVE MECHANISMS IN THE INTERFACE BETWEEN SPIROCHETE, TICK AND HOST

螺旋体、蜱虫和宿主之间界面的保护机制

• 批准号: 6268036
• 负责人: FRED S KANTOR
• 金额: $ 16.52万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6268036
• 关键词: Borrelia; Ixodes; Lyme disease; SDS polyacrylamide gel electrophoresis; active immunization; antigens; bactericidal immunity; communicable disease transmission; disease /disorder model; disease vectors; genetic library; guinea pigs; host organism interaction; humoral immunity; immunity; immunoglobulin G; laboratory mouse; laboratory rabbit; molecular cloning; monoclonal antibody; passive immunization; protein purification; salivary glands; surface antigens; tissue /cell culture; western blottings

Acquired resistance to ticks was reported in the late l93Os. These findings have been confirmed and extended to guinea pigs and rabbits using several species of ticks by several investigators including ourselves. The proposed project is to identify the molecular basis of the antigens involved in tick immunity and study its effect on the antigens of the B. burgdorferi carried by the ticks and upon the transmission of Lyme borreliosis. Specifically models of tick protective immunity will be established in guinea pigs and in rabbits. Antibodies shown to be capable of passively protecting recipients will be purified using chemical and immunoabsorbent methods. Antigen specificity of lymphocytes from tick protected animals and from clones will be characterized. Tick Salivary and midgut antigens will be obtained from the appropriate organs of Ixodes scapularis and from supernatants and homogenates of tissue cultures; these antigens will be purified by chemical and immunological means. Such antigens will be used to produce tick immunity in the models chosen. With polyclonal and monoclonal antibodies obtained from tick-or purified antigen-sensitized animals DNA libraries will be screened. Such libraries, prepared from stimulated tick salivary glands and midguts, will be used to clone genes encoding protective antigens. Using immune guinea pigs and mice the effect of anti-tick immunity on the surface antigens of tick-borne Borrelia burgdorferi will be studied and the ability of infected ticks to transmit disease to tick-immune host determined. The potential synergistic effects of dual anti-tick and anti- Osp A immunity on the ability of infected ticks to transmit Lyme borreliosis will be investigated in the mouse model.

1930年代末曾报道过对蜱的获得性抗性。 这些 研究结果已经得到证实，并扩展到豚鼠和兔子， 包括我们在内的几位研究者对几种蜱虫进行了研究。 拟议的项目是确定抗原的分子基础 参与蜱免疫并研究其对B抗原的影响。 由蜱虫和莱姆传播的伯氏菌 疏螺旋体病 特别是蜱保护性免疫模型将建立在 豚鼠和兔子。抗体显示能够被动地 保护受体将使用化学和免疫吸附剂进行纯化， 方法.蜱类保护动物淋巴细胞的抗原特异性 和克隆的特征。 蜱唾液和中肠抗原将从适当的 肩胛硬蜱的器官和从上清液和匀浆 组织培养物;这些抗原将通过化学和生物学方法纯化， 免疫学手段。 这些抗原将用于产生蜱免疫 在选择的模型中。 用从蜱中获得的或纯化的多克隆和单克隆抗体 将筛选抗原致敏的动物DNA文库。 等 从刺激的蜱唾液腺和中肠制备的文库将 用于克隆编码保护性抗原的基因。 采用免疫豚鼠和小鼠，观察抗蜱免疫对小鼠免疫功能的影响。 将研究蜱传伯氏疏螺旋体的表面抗原， 受感染蜱将疾病传播给蜱免疫宿主的能力 测定 双重抗蜱和抗- Osp A免疫对感染蜱传播莱姆病能力的影响 将在小鼠模型中研究疏螺旋体病。