Antigenic variation of Anaplasma marginale

描述(由申请人提供)：研究建议：埃立克次体和相关的壁虱传播的人和动物立克次体病原体的发病机制与它们逃避免疫系统的能力直接相关。表面蛋白的抗原变异是所有埃立克病原体共同的主要逃避策略，通常涉及非常相似的抗原。边缘无浆体是一种牛的病原体，与人类粒细胞性埃立克体病的病原体无浆体(埃利希菌)吞噬细胞密切相关。牛无浆体病的研究为在受控条件下研究自然动物模型中抗原变异的机制提供了一个独特的机会。本项目将研究宿主免疫系统识别的主要抗原MSP3及其相关抗原的抗原变异的机制和程度。它还将研究不同的环境：哺乳动物宿主、壁虱载体和体外培养物对边缘毛滴虫克隆株MSP3抗原表达的影响。 候选人：首席调查员是一名兽医，在寄生虫和壁虱传播疾病方面有丰富的现场经验，并有成为该领域独立研究人员的强烈愿望。在为此做准备时，候选人已经注册了传染病博士项目，并完成了统计学、分子生物学、免疫学和致病学的课程，并已被接纳为候选人。这项建议将使他成为一名独立的研究人员，并将有助于阐明动物和人类中媒介传播病原体的致病机制。研究人员希望将这些发现和获得的专业知识应用于创新控制策略的开发。 环境：培训将在临床和基础科学家互动的环境中进行。导师在病媒传播病原体的发病机制和免疫反应方面拥有丰富的经验，并成功地培训了之前的候选人。该计划为拟议的培训提供了一个很好的框架。

DESCRIPTION (provided by applicant): Research proposal: The pathogenesis of ehrlichial and related tick-borne rickettsial pathogens of humans and animals is directly linked to their ability to evade the immune system. Antigenic variation of surface proteins is a major evasion strategy common to all ehrlichial pathogens, often involving very similar antigens. Anaplasma marginale, a bovine pathogen, is closely related to Anaplasma (Ehrlichia) phagocytophila, the causative agent of human granulocytic ehrlichiosis. Investigations of bovine anaplasmosis offer a unique opportunity to study the mechanisms of antigenic variation in a natural animal model under controlled conditions. This project will examine the mechanisms and extent of antigenic variation of MSP3, the major antigen recognized by the hosts immune system, and related antigens. It will also investigate the influences of different environments: the mammalian host, the tick vector and in-vitro cultures, on the expression of the MSP3 antigen in a clonal line of A. marginale. The candidate: The principal investigator is a veterinarian with extensive field experience in parasitic and tick-borne diseases and with a strong desire to become an independent researcher in this field. In preparation for this, the candidate has enrolled in an infectious disease Ph.D. program and has completed courses in statistics, molecular biology, immunology and pathogenesis and has been admitted to candidacy. This proposal will allow his development as an independent researcher and will help elucidating pathogenic mechanisms of vector-borne pathogens in animals and humans. The investigator hopes to apply these findings and the expertise gained toward the development of innovative control strategies. Environment: The training will occur in an interactive environment of clinical and basic scientists. The mentors have extensive experience in the pathogenesis of and immune responses to vector-borne pathogens and have successfully trained previous candidates. The program provides an excellent framework for the proposed training.