Early cellular immune responses to EBV

针对 EB 病毒的早期细胞免疫反应

• 批准号: 7250262
• 负责人: SUMITA BHADURI-MCINTOSH
• 金额: $ 13.66万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7250262
• 关键词: Acquired Immunodeficiency Syndrome; Address; Advisory Committees; Antibodies; Apoptosis; Apoptosis Inhibitor; Apoptotic; Aprotinin; Autologous; B-Lymphocytes; BIRC4 gene; Biological Assay; Biological Models; Blocking Antibodies; Brefeldin A; Burkitt Lymphoma; CD4 Positive T Lymphocytes; CD44 Antigens; CD8B1 gene; Caspase; Caspase Inhibitor; Cell Line; Cell Surface Receptors; Cell surface; Cells; Cellular Immunity; Cellular Immunology; Cellular biology; Central Nervous System Lymphoma; Childhood; Cleaved cell; Coculture Techniques; Communicable Diseases; Condition; Cytochromes; Cytoplasmic Granules; Dactinomycin; Decitabine; Detection; Development; Diagnostic; Disease; Doctor of Philosophy; Educational Curriculum; Effector Cell; Enzymes; Epstein-Barr Virus Infections; Epstein-Barr Virus latency; Exhibits; Exocytosis; Experimental Models; Fellowship; Flow Cytometry; Gene Expression; Genes; Glycoproteins; Goals; Granzyme; Health; Hour; Human Herpesvirus 4; IL2 gene; IL4 gene; Immune; Immune response; Immune system; Immunologist; Immunology; In Vitro; Individual; Infection; Infection prevention; Infectious Mononucleosis; Interleukin-12; Interleukin-15; Interleukin-2; Interleukin-4; Knowledge; Label; Laboratories; Life; Ligands; Link; Lymphoid; Lymphoproliferative Disorders; Lytic; MHC Class I Genes; MHC Class II Genes; Maintenance; Mediating; Memory; Mentors; Mitochondria; Mitochondrial Proteins; Modification; Molecular; Monoclonal Antibodies; Movement; Nasopharynx Carcinoma; Natural Killer Cells; Nature; Non-Hodgkin' s Lymphoma; Oligonucleotides; Organ; Outcome; Pathway interactions; Patients; Pattern; Pediatrics; Peripheral Blood Mononuclear Cell; Phenotype; Play; Poly(ADP-ribose) Polymerases; Population; Principal Investigator; Program Development; Proteins; Publishing; Recombinant Proteins; Recombinants; Research; Residencies; Resources; Role; Role playing therapy; SELL gene; Serine Proteinase Inhibitors; Sorting - Cell Movement; Specificity; Spottings; Staging; Staining method; Stains; Structure; Surface; System; T memory cell; T-Lymphocyte; TNFRSF10B gene; TNFSF10 gene; TRAMP protein; Therapeutic; Time; Training; Training Programs; Viral Antigens; Viral Proteins; Virus; Work; annexin A5; apoptotic protease-activating factor 1; career; caspase-3; caspase-activated deoxyribonuclease; cell killing; cell type; cohort; cytokine; cytotoxic; cytotoxicity; design; dye 55; experience; fluorexon; immunosuppressed; infected B cell; inhibitor/antagonist; interest; killings; macrophage; memory CD4 T lymphocyte; monocyte; multicatalytic endopeptidase complex; programs; receptor; research study; response; skills; success; tool; tumor; virology; virus infection mechanism

DESCRIPTION (provided by applicant): This proposal outlines a 5-year training program for the development of an academic career in Pediatric Infectious Disease. The candidate has completed residency training in Pediatrics, Ph.D. training in Molecular and Cell Biology, and fellowship training in Infectious Disease. She is now in the midst of enhancing her scientific skills through a unique blend of interdepartmental resources and expertise. The candidate's goal is to develop a command of cellular immunology as it relates to viruses by integrating EBV immunology research and a structured curriculum to enhance scientific knowledge in the fields of both virology and cellular immunology. Dr. George Miller, a renowned EBV virologist will mentor the candidate's scientific development. To enhance the experience, an advisory committee of highly respected immunologists studying diverse aspects of cellular immunology will provide scientific and career guidance. The candidate's research will examine the immune responses in the early stages of primary EBV infection and in the early stages of control of outgrowth of latently infected B cells in EBV-immune individuals. These questions will be addressed using a relevant and unique model experimental system that the candidate has developed. The goals are: 1. To identify the cells important in the initial response to EBV-LCL during primary infection and for the prevention of outgrowth of latently infected B cells in EBV seropositive individuals. 2. To determine if the responding cells are cytotoxic to LCL and characterize the mechanism of cell killing. 3. To experimentally modulate the composition and nature of the immune response by using exogenous molecules. This study will, for the first time, allow glimpses into the earliest interactions between the immune system and EBV without modification or amplification of the immune response. It is also expected to enhance the understanding of EBV lymphoproliferative diseases and have potential diagnostic and therapeutic implications.

描述（由申请人提供）：本提案概述了一个为期5年的培训计划，为儿科传染病的学术生涯的发展。候选人已完成儿科住院医师培训，博士学位。分子和细胞生物学培训，传染病研究金培训。她现在正在通过跨部门资源和专业知识的独特组合来提高她的科学技能。 候选人的目标是通过整合EBV免疫学研究和结构化课程来提高病毒学和细胞免疫学领域的科学知识，从而掌握与病毒相关的细胞免疫学。著名的EBV病毒学家乔治米勒博士将指导候选人的科学发展。为了增强经验，一个由研究细胞免疫学各个方面的德高望重的免疫学家组成的咨询委员会将提供科学和职业指导。 候选人的研究将检查原发性EBV感染早期阶段的免疫反应，以及EBV免疫个体中潜伏感染B细胞生长控制的早期阶段。这些问题将使用候选人开发的相关和独特的模型实验系统来解决。目标是：1.鉴定在原发性感染期间对EBV-LCL的初始应答中重要的细胞，以及在EBV血清阳性个体中预防潜伏感染的B细胞的生长。2.确定应答细胞是否对LCL具有细胞毒性，并表征细胞杀伤机制。3.通过使用外源性分子实验性调节免疫反应的组成和性质。这项研究将首次让我们了解免疫系统和EBV之间最早的相互作用，而不会改变或放大免疫反应。这也有望提高对EBV淋巴增生性疾病的认识，并具有潜在的诊断和治疗意义。