IMMUNE RESPONSE TO HERPES SIMPLEX VIRUS IN PREGNANCY

妊娠是一种部分免疫功能低下的状态， 由各种病原体引起的感染， 单纯病毒（HSV）耐受性差。 除了直接 遇到产妇发病率，HSV感染可以是 传播给胎儿和新生儿，导致高急性 围产期死亡率和长期神经系统后遗症 幸存者 自然杀伤细胞毒性（NKC）和抗体- 依赖性细胞毒性（ADCC）是主要的 免疫防御系统被认为是发挥关键作用， 在HSV感染。 该项目的具体目标是 定义和描述妊娠期的免疫反应。 使用体外效应/靶细胞模型， 将对单核效应细胞进行NKC系列检测， 整个妊娠期的ADCC活性，特别是抗HSV- 感染了Chang的肝脏靶细胞 根据申请人的 初步数据表明，NKC缺乏状态， 妊娠，单细胞琼脂糖测定将用于进一步 根据其更基本的功能来定义这种赤字 组件，即，细胞粘附、裂解和再循环。 已知 将在体外测试免疫调节剂的能力 来重建妊娠相关的NKC缺陷 此外，对这一机制的调查表明， 免疫调节的发生将通过检查 细胞花生四烯酸脂氧合， 重组 这些目标的实现将改善 我们对HSV感染的免疫学的理解， 怀孕，并提供一个更合理的方法， 预防和控制这种传染病和病态过程。 本提案概述的目标在逻辑上是可以实现的， 将提供一个起点，开始我的发展， 独立研究员在这一领域的研究。 我最近的工作 为我提供了一项具有挑战性的研究 重点和方法来开发它。我的两个 赞助商和我的系主任已经明确告诉我 这表明他们继续支持这些努力。 这 包括技术援助，实验室支持， 免除其他临床责任。 作为一个机构， 德克萨斯大学医学院因其 学术成就进一步强调了这一丰富性 一个年轻的调查员。

Pregnancy represents a partially immunocompromised state in which infections caused by various pathogens such as herpes simplex virus (HSV) are poorly tolerated. Aside from the direct maternal morbidity encountered, HSV infections can be transmitted to the fetus and newborn resulting in a high acute perinatal mortality and long-term neurologic sequelae in survivors. Natural killer cell cytotoxicity (NKC) and antibody- dependent cellular cytotoxicity (ADCC) are primary immunodefense systems which are thought to play a pivotal role in HSV infection. The specific aims of this project set out to define and characterize these immune responses in pregnancy. Using an in vitro effector/target cell model, pregnant women's mononuclear effector cells will be serially tested for NKC and ADCC activity throughout gestation, specifically against HSV- infected Chang liver target cells. Based on the applicant's preliminary data which suggests an NKC deficient state in pregnancy, a single cell agarose assay will be used to further define this deficit in terms of its more basic functional components, i.e., cellular adhesion, lysis, and recycling. Known immunoregulatory agents will be tested in vitro for their ability to reconstitute this pregnancy-associated NKC deficit. Additionally, an investigation into the mechanism by which this immunoregulation occurs will be undertaken by examining cellular arachidonic acid lipoxygenation following pharmacologic reconstitution. Achievement of these objectives will improve our understanding of the immunology of HSV infection in pregnancy and provide a more rational approach to the prevention and control of this infectious and morbid process. The goals outlined to this proposal are logistically obtainable and would provide a starting point to begin my development as an independent investigator in this field of study. My recent work with Dr. Steve Kohl has provided me with a challenging research focal point and the methodology to develop it. Both my sponsors, and my department chairman, have given me clear indications of their continued support in these endeavors. This includes technical assistance, laboratory support, and adequate freedom from other clinical responsibilities. As an institution, The University of Texas Medical School is well recognized for its academic achievements further emphasizing the richness of this environment for a young investigator.