Origins of specialized Mucosal Lymphocyte Subsets and Immunoglobulin Isotypes

特殊粘膜淋巴细胞亚群和免疫球蛋白同种型的起源

基本信息

批准号：
7633248
负责人：
MICHAEL FREDERICK CRISCITIELLO
金额：
$ 10.8万
依托单位：
TEXAS A&M AGRILIFE RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-15 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7633248
关键词：
Adult Advocate African Allergens Allergic Amphibia Animal Model Animals Antibodies Antigen Receptors Antigens Architecture Autoimmunity Award Biological Response Modifiers Biology Cells Communicable Diseases Comprehension Crohn&apos s disease Data Data Set Dependence Development Disease Educational process of instructing Equilibrium Evolution Failure FarGo Food Generations Genetic Goals Gut associated lymphoid tissue Hypersensitivity Immune Immune Tolerance Immune system Immunity Immunization Immunoglobulin A Immunoglobulin Class Switching Immunoglobulin Isotypes Immunoglobulin M Immunoglobulins Immunohistochemistry Immunology In Situ Hybridization Individual Intestines Investigation Knowledge Lamina Propria Left Length Light Lymphocyte Lymphocyte Subset Lymphoid Lymphoid Tissue Mammals Maps Mediating Modeling Molecular Monoclonal Antibodies Mucosal Immunity Mus Natural History Nurses Oral Oral Administration Organism Phylogenetic Analysis Physicians Physiological Physiology Plasma Cells Play Population Postdoctoral Fellow Postdoctoral Individual National Research Service Award Rana Recording of previous events Regulation Research Research Personnel Role Route Running Secure Seeds Shark Stimulus Strategic Planning Surface System T-Cell Receptor T-Lymphocyte T-Lymphocyte Subsets Testing Thymectomy Thymus Gland Time Tissue Model Tissue Stains Tissues Training Ulcerative Colitis Upper arm Vertebrates Work Xenopus Xenopus sp.analog base career cold blooded vertebrate comparative fundamental research gastrointestinal epithelium human disease insight interest intraperitoneal macrophage man member novel strategies oral tolerance pathogen preference professor programs receptor response tool

项目摘要

DESCRIPTION (provided by applicant): The mammalian mucosal immune system is the largest lymphoid compartment, encounters the most diverse antigenic load, and is breached or infected by the great majority of infectious diseases worldwide. Studies of gut associated lymphoid tissues (GALT) in mouse and man have provided much insight into the specialized lymphocyte subsets and immunoglobulin (Ig) isotypes that manage the balance between tolerance to food antigens and commensals and activation against pathogen. However little is known of comparative immunology of GALT. This is especially true in the cold-blooded vertebrates where the system arose. I propose to test the hypothesis that specialized T cell subsets and Ig isotypes in the gut are an ancient and fundamental part of our immune system that were necessary early in the history of adaptive immunity. The shark and frog GALT are the models in which this hypothesis will be tested. In shark the molecular characterization of intestinal lymphocytes will focus on the repertoire of special subsets such as the new NAR-TcR T cell. Tissue staining will map these cells anatomically within the gut epithelia or lamina propria. The second aim will employ the experimental advantages and immunological tools of the African clawed frog system to investigate which isotypes and mechanisms are conserved in the humoral mucosal compartment. Oral immunizations will test route of administration, thymus dependence of class switch, generation of oral tolerance in the periphery and light chain isotype function. GALT study in lower vertebrates will teach us what is phylogenetically basic in mediating defense and tolerance. Additionally, we will gain insight into the early lymphocyte subpopulations and repertoires of the adaptive immune system. By allowing me protected time for this fundamental research as a new Assistant Professor, a stronger application will be possible for my first R01 in three years. This work will seed my independent career investigating the origins and natural history of our immune system to better able the physician to modify repertoires for the amelioration of disease. A unifying theme in the four cornerstones of NIAID's strategic plan is the need for a better comprehension of lymphocyte regulation from the extremes of failure of the repertoire to autoimmunity and allergy, and comparative work studying GALT immunology in model primitive vertebrates is ripe to yield such understanding.

描述（由申请人提供）：哺乳动物粘膜免疫系统是最大的淋巴室，遇到最多样化的抗原负荷，并被全世界大多数感染性疾病违反或感染。小鼠和人类中肠道相关淋巴组织（GALT）的研究提供了对专门的淋巴细胞亚群和免疫球蛋白（IG）同种型的深入了解，这些亚群（IG）同种型管理对食物抗原的耐受性与赋予病原体的耐受性之间的平衡。然而，对Galt的比较免疫学知之甚少。在系统出现的冷血脊椎动物中尤其如此。我建议检验以下假设：肠道中专门的T细胞亚群和Ig同种型是我们免疫系统的古老而基本的部分，在适应性免疫史的早期是必不可少的。鲨鱼和青蛙galt是对该假设进行检验的模型。在鲨鱼中，肠道淋巴细胞的分子表征将集中在特殊子集的曲目上，例如新的NAR-TCR T细胞。组织染色将在肠道上皮或椎板中解剖学绘制这些细胞。第二个目的将采用非洲爪蛙系统的实验优势和免疫学工具来研究哪种同种型和机制在体液粘膜室中是保守的。口服免疫将测试给药途径，班级转换的胸腺依赖性，外围和轻链同型功能中的口服耐受性。在下脊椎动物中的Galt研究将教会我们在介导防御和容忍度中的系统发育基础上是什么。此外，我们将深入了解自适应免疫系统的早期淋巴细胞亚群和曲目。通过让我为这项新的助理教授提供保护时间，这将是我三年来我的第一个R01的更强大应用。这项工作将使我的独立职业生涯调查我们的免疫系统的起源和自然历史，以更好地改善医生的疾病改善库。 NIAID战略计划的四个基石中的一个统一主题是，需要更好地理解淋巴细胞调节，从曲目失败到自动免疫和过敏，以及对模型原始脊椎动物中Galt免疫学研究Galt免疫学的比较工作，以产生这种理解，以产生这种理解的理解。