INNATE IMMUNITY IN SIV INFECTION

SIV 感染的先天免疫

• 批准号: 8357512
• 负责人: Aftab A. Ansari
• 金额: $ 5.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357512
• 关键词: Acute; Address; Antigens; Biopsy; Blood; Cells; Colon; Disease; Funding; Genetic; Grant; HIV; Immune System Diseases; Immune response; Immunologic Deficiency Syndromes; Immunologic Monitoring; Individual; Infection; Irrigation; Macaca mulatta; Major Histocompatibility Complex Gene; Monitor; National Center for Research Resources; Natural Immunity; Natural Killer Cells; Organism; Predisposition; Primates; Principal Investigator; Research; Research Infrastructure; Resources; SIV; Small Intestines; Source; United States National Institutes of Health; Virus Replication; cost; in vivo; receptor; rectal; response; senescence

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. nfection with SIVmac251. Individuals respond very differently to infection with HIV leading to highly variable courses of disease post infection. This proposal aims to investigate a mechanism of natural immunosurveillance, termed "natural killer cells" (NK) that besides monitoring cells in the body for senescence (being too old to function properly) also sense deviation from the "normal" at the cell level. We have found that similar to the major histocompatibility complex (MHC) genes that constitute an organism's ID and dictate many of the antigen specific immune responses, innate responses also may vary due to genetic inheritance. The application will therefore focus on rhesus macaques with comparable MHC genes but distinct NK associated receptors to correlate distinct receptors with susceptibility to simian immunodeficiency (SIV) induced disease. The proposal will also address the impact of NK inhibition during acute infection on the disease course and finally whether this mechanism can be boosted by providing additional NK in vivo and whether such boost has impact on virus replication, the quality of the ensuing adaptive immune responses and disease course. All studies will investigate blood, rectal, colon and small bowel biopsies as well as broncholveolar lavages (BAL) to monitor the effect of NK before and after infection with SIVmac251.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 SIVmac251 感染。个体对艾滋病毒感染的反应截然不同，导致感染后病程差异很大。该提案旨在研究一种自然免疫监视机制，称为“自然杀伤细胞”（NK），除了监测体内细胞的衰老（太老而无法正常运作）之外，还可以感知细胞水平上与“正常”的偏差。我们发现，与构成生物体 ID 并决定许多抗原特异性免疫反应的主要组织相容性复合体 (MHC) 基因类似，先天反应也可能因遗传而异。因此，该申请将重点关注具有类似 MHC 基因但具有不同 NK 相关受体的恒河猴，以将不同受体与猿猴免疫缺陷 (SIV) 诱发疾病的易感性相关联。该提案还将讨论急性感染期间 NK 抑制对疾病进程的影响，以及最后是否可以通过在体内提供额外的 NK 来增强这种机制，以及这种增强是否会影响病毒复制、随后的适应性免疫反应的质量和病程。所有研究都将调查血液、直肠、结肠和小肠活检以及支气管肺泡灌洗液 (BAL)，以监测 SIVmac251 感染前后 NK 的效果。