INNATE IMMUNITY IN SIV INFECTION

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 用SIVmac 251转染。个体对艾滋病毒感染的反应非常不同，导致感染后的病程差异很大。该提案旨在研究自然免疫监视的机制，称为“自然杀伤细胞”（NK），除了监测体内细胞的衰老（太老而不能正常工作）外，还可以在细胞水平上感知偏离“正常”的情况。我们已经发现，类似于构成生物体ID并决定许多抗原特异性免疫应答的主要组织相容性复合体（MHC）基因，先天性应答也可能由于遗传遗传而变化。因此，本申请将集中于具有可比MHC基因但具有不同NK相关受体的恒河猴，以将不同受体与对猿猴免疫缺陷（SIV）诱导的疾病的易感性相关联。该提案还将解决急性感染期间NK抑制对疾病进程的影响，以及最终是否可以通过在体内提供额外的NK来增强这种机制，以及这种增强是否对病毒复制、随后的适应性免疫应答的质量和疾病进程产生影响。所有研究将调查血液、直肠、结肠和小肠活检以及支气管肺泡灌洗（BAL），以监测在用SIVmac 251感染之前和之后NK的作用。

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.