INNATE IMMUNITY IN SIV INFECTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 个体对感染艾滋病毒的反应非常不同，导致感染后的病程变化很大。这项建议旨在研究一种自然免疫监测机制，称为自然杀伤细胞(NK)，除了监测体内细胞的衰老(太老而不能正常运作)外，还在细胞水平上感觉到偏离正常的状态。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，先天性反应也可能因遗传而异。因此，这项应用将集中在具有类似MHC基因但具有不同的NK相关受体的恒河猴身上，以使不同的受体与猴免疫缺陷(SIV)诱导的疾病的易感性相关。 该提案还将讨论在急性感染期间抑制NK对病程的影响，以及最终是否可以通过在体内提供额外的NK来增强这一机制，以及这种增强是否对病毒复制、随后的适应性免疫反应的质量和病程产生影响。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(BAL)，以监测感染SIVmac251前后NK细胞的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.