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IMMUNE RESPONSE TO HERPES SIMPLEX VIRUS IN PREGNANCY

妊娠期单纯疱疹病毒的免疫反应

基本信息

批准号：
3081344
负责人：
BERNARD GONIK
金额：
$ 6.31万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-08-01 至 1990-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3081344
关键词：
Alphaherpesvirinae T lymphocyte antibody dependent killer cell arachidonate cell adhesion cell mediated cytotoxicity human tissue immunomodulators immunoregulation indomethacin interferons interleukin 2 microorganism immunology pregnancy immunology pregnancy infection respiratory oxygenation

项目摘要

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.

怀孕代表着部分免疫功能低下的状态由疱疹等多种病原体引起的感染单纯疱疹病毒（HSV）的耐受性很差。除了直接产妇发病时，HSV 感染可传播给胎儿和新生儿，导致高度急性围产期死亡率和长期神经系统后遗症幸存者。自然杀伤细胞的细胞毒性（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发挥着关键作用在HSV感染中。该项目的具体目标是定义和表征怀孕期间的这些免疫反应。使用体外效应器/靶细胞模型，孕妇单核效应细胞将进行 NKC 和 ADCC 活性贯穿整个妊娠期，特别针对 HSV- 感染Chang肝脏靶细胞。根据申请人的初步数据表明 NKC 缺陷状态怀孕时，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缺陷成分，即细胞粘附、裂解和回收。已知免疫调节剂的能力将在体外进行测试重建这种与妊娠相关的 NKC 缺陷。此外，还对这一机制进行了调查免疫调节的发生将通过检查来进行药物作用后细胞花生四烯酸脂氧合重构。这些目标的实现将得到改善我们对 HSV 感染免疫学的理解怀孕并提供更合理的方法预防和控制这种传染性和病态过程。本提案概述的目标在逻辑上是可以实现的，并且将为我的发展提供一个起点该研究领域的独立研究者。我最近的工作与史蒂夫·科尔博士一起为我提供了一项具有挑战性的研究焦点及其制定方法。都是我的赞助商和我的系主任已经给我明确的表明他们对这些努力的持续支持。这包括技术援助、实验室支持和足够的免于其他临床责任。作为一个机构，德克萨斯大学医学院以其学术成就进一步强调了这一点的丰富性一个年轻研究者的环境。