Mechanisms and Consequences of Immune Activation in HIV Infected Children

HIV 感染儿童免疫激活的机制和后果

基本信息

批准号：
8320908
负责人：
Alka Khaitan
金额：
$ 13.25万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-16 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8320908
关键词：
Academic Medical Centers Accounting Acquired Immunodeficiency Syndrome Adult Affect Anti-Inflammatory Agents Anti-inflammatory Antigens Bacterial Translocation Basic Science Biological Markers Blood Circulation CD8B1 gene Cells Cessation of life Child Childhood Chronic Clinical Clinical Research Core Facility Development Development Plans Disease Progression Ensure Environment Equilibrium Failure Foundations Goals HIV HIV Infections Immune Immune System Diseases Immune response Immune system Immunoglobulins Immunologic Factors Immunologic Markers Immunologics Immunosuppression Immunotherapy In Vitro Infection Inflammatory Institution K-Series Research Career Programs Knowledge Laboratory Research Lead Learning Life Mentors Mentorship Mucins New York Perinatal Phenotype Play Prevalence Prognostic Factor Property Regulation Regulatory T-Lymphocyte Reporting Research Research Personnel Resources Role Science Scientist Solid Structure T cell differentiation T cell response T-Cell Activation T-Lymphocyte T-Lymphocyte Subsets Technology Therapeutic Intervention Thinking Time Translational Research United States Viral antiretroviral therapy base career development exhaust exhaustion experience functional restoration immune activation in vivo infancy infant death insight microbial mortality novel pediatric human immunodeficiency virus infection prevent programs public health relevance research study senescence skills transmission process vaccine development

项目摘要

DESCRIPTION (provided by applicant): The primary goals of this Mentored Career Development award are to develop the knowledge, skills, and experience necessary to progress to an independent researcher. The proposed career development plan combines basic science courses, didactic clinical research sessions, laboratory research, and mentored learning to ensure a facile transition to independence. Structured coursework will provide a solid foundation of knowledge while mentored proposal enactment will encourage hypothesis driven research and independent thinking. The New York University Medical Center will provide a rich academic environment with a diverse group of scientists in basic and clinical translational research and multiple core facilities and resources to support the state-of-the-art technologies and science within the institution. Within this environment, I will have the mentorship of Drs. Derya Unutmaz and William Borkowsky to provide the guidance necessary to develop into a successful researcher. The proposed research study is aimed to dissect the mechanisms and consequences of immune activation in HIV infected children. Although immune activation is a poor prognostic factor in both adults and children, we postulate that stimulation of an immature immune system differs in its mechanisms and consequences compared with adults and contributes to rapid disease progression in children. The specific goals are to determine: 1) Immunologic and microbial correlates of immune activation in HIV infected children; and 2) whether immune activation leads to T cell exhaustion in HIV infected children. We will examine novel T cell subsets, Th17 and T regulatory cells, and immunologic factors affecting activation that are largely unexplored in HIV infected children. An understanding of the immunological basis of T cell activation during HIV infection opens the possibility of identifying novel biomarkers or immunotherapies. Public Health Relevance: The proposed research will evaluate the effects of HIV on the immune system in HIV infected children. An understanding of how immune responses contribute to HIV disease progression may lead to vaccine development or novel immunotherapies.

描述（由申请人提供）：该导师职业发展奖的主要目标是培养成为独立研究员所需的知识、技能和经验。拟议的职业发展计划结合了基础科学课程、教学临床研究课程、实验室研究和指导学习，以确保轻松过渡到独立。结构化课程将提供坚实的知识基础，而指导提案的制定将鼓励假设驱动的研究和独立思考。纽约大学医学中心将提供丰富的学术环境，拥有从事基础和临床转化研究的多元化科学家群体，以及多个核心设施和资源，以支持机构内最先进的技术和科学。在这样的环境下，我将得到Drs.的指导。 Derya Unutmaz 和 William Borkowsky 为成为一名成功的研究人员提供必要的指导。拟议的研究旨在剖析艾滋病毒感染儿童免疫激活的机制和后果。尽管免疫激活对于成人和儿童来说都是一个不良的预后因素，但我们假设，与成人相比，刺激不成熟的免疫系统的机制和后果不同，并且会导致儿童疾病的快速进展。具体目标是确定： 1) HIV 感染儿童免疫激活的免疫学和微生物相关性； 2) 免疫激活是否会导致 HIV 感染儿童的 T 细胞耗竭。我们将研究新的 T 细胞亚群、Th17 和 T 调节细胞，以及影响激活的免疫因素，这些因素在 HIV 感染儿童中基本上尚未被探索。了解 HIV 感染期间 T 细胞激活的免疫学基础，为识别新的生物标志物或免疫疗法提供了可能性。公共卫生相关性：拟议的研究将评估艾滋病毒对艾滋病毒感染儿童免疫系统的影响。了解免疫反应如何促进艾滋病毒疾病进展可能会导致疫苗开发或新型免疫疗法。