T Cell Memory and Protection Against Placental Malaria

T 细胞记忆和针对胎盘疟疾的保护

• 批准号: 6511625
• 负责人: JULIE M MOORE
• 金额: $ 32.4万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6511625
• 关键词: RNase protection assay; T lymphocyte; antigen antibody reaction; blood chemistry; cellular immunity; chemokine; clinical research; cytokine receptors; disease /disorder proneness /risk; enzyme linked immunosorbent assay; flow cytometry; human pregnant subject; immunocytochemistry; immunologic memory; immunoregulation; malaria; pathologic process; placental transfer; pregnancy immunology; pregnancy infection; receptor expression; women's health

DESCRIPTION: (provided by the applicant): Women living in high malaria endemic areas are at an increased risk for Plasmodial infection during pregnancy. The prevalence and density of parasitemia is highest among primigravidae, and commonly leads to maternal anemia and low birth weight. The placenta is especially susceptible to infection, with parasite densities being frequently higher than those in the peripheral blood. The underlying immunologic basis for the increased susceptibility of pregnant women (and their placentae) to malaria and the dependence of this susceptibility on gravidity are poorly understood. The objective of this application is to determine the cellular immune mechanisms that mediate resistance to placental malaria. The central hypothesis of this proposal is that the decreased susceptibility of multigravidae to placental infection is dependent on development of tissue-specific, T cell-mediated, memory immune responses against malaria in the placental blood. The specific aims are to 1) to characterize cell-mediated immune memory in the placenta and identify the elements that contribute to protection against placental malaria, and 2) determine the role of chemokines in the regulation of memory immune responses against malarial infection in the placenta. Comparison of peripheral and placental blood collected at delivery using flow cytometry, ELISPOT, ELISA, and RNase protection assays, and examination of placental tissue using immunohistochemistry, will be used to 1) identify the phenotypic and functional components of placental cellular memory responses to malaria that distinguish multigravidae from primigravidae, susceptible women from resistant women, and pathogenic responses from protective responses, 2) determine the extent to which these placental responses are distinct from those in the peripheral blood, and 3) determine how differential, local chemokine expression patterns in the placenta influence memory immune responses to placental malaria. Expanded knowledge of protective, anti-malarial immune mechanisms that are developed and maintained in the immunomodulated state of pregnancy will facilitate application of immunologic tools, such as malaria vaccines when they become available, to the prevention and control of malaria in pregnant women. Preventing malaria in pregnant women will significantly reduce both the disease burden of women in the developing world and the loss of infants in their first few months of life.

描述：（由申请人提供）：居住在疟疾高疟疾的妇女 在怀孕期间，区域面临着质质感染的风险。这 寄生虫血症的患病率和密度最高 通常会导致产妇贫血和低出生体重。胎盘是 特别容易感染，寄生虫密度经常 高于外周血中的人。基础免疫基础 孕妇（及其胎盘）对疟疾的敏感性增加 并且这种敏感性对质感的依赖性知之甚少。 该应用的目的是确定细胞免疫 介导对胎盘疟疾的抗性的机制。中心假设 该提议的是，多格维德科的敏感性降低了 胎盘感染取决于组织特异性，T的发展 细胞介导的胎盘血液中对疟疾的记忆免疫反应。 具体目的是1）表征细胞介导的免疫记忆 胎盘并确定有助于保护的要素 胎盘疟疾和2）确定趋化因子在调节中的作用 对胎盘中疟疾感染的记忆免疫反应。比较 使用流式细胞术时分娩时收集的外围和胎盘血的血液 ELISPOT，ELISA和RNase保护分析和检查胎盘检查 使用免疫组织化学的组织将用于1）识别表型 和胎盘细胞记忆对疟疾的功能成分 这将Multigravidae与Primigravidae区分开，易感妇女与 抗药性妇女和保护性反应的致病反应，2） 确定这些胎盘反应的程度 在外周血中，3）确定局部趋化因子的差异 胎盘中的表达模式会影响记忆免疫反应 胎盘疟疾。扩大保护性，抗疟疾免疫的知识 在免疫调节状态中开发和维持的机制 怀孕将促进免疫工具的应用，例如疟疾 疫苗可用时，可以预防和控制疟疾 在孕妇。预防孕妇的疟疾将显着 减轻了发展中国家妇女的疾病负担和失去 婴儿在生命的头几个月。