MALARIA AND IMMUNE RESPONSES OF CORD BLOOD CELLS

由恶性疟原虫引起的疟疾的模式受到 环境因素，包括地方性和强度 传输 例如，居住在低流行地区的儿童 通常患有以脑型疟疾为特征的严重疾病， 而居住在完全流行地区的儿童更有可能 患有寄生虫血症伴严重贫血。 很 免疫过程可能会对免疫系统产生深远的影响。 疾病的临床表现与寄生虫密度无关 在血液中。 因为胎盘是血液阶段的储存库 疟原虫抗原，我们假设婴儿出生的母亲， 在怀孕期间经历疟疾产生耐受性或抑制性 在子宫内血液阶段抗原的机制。在随后的疟疾期间 感染，与年龄相关的保护性免疫力的获得是 由T细胞库定义，T细胞库由早期的 接触疟疾抗原。 我们建议受影响的新生儿 免疫反应是通过表达特征性的 T细胞和单核细胞的表型标志物和免疫功能 可以从脐带血细胞中提取 为审查这些问题，建议实现以下具体目标， 从孕妇分娩时获得的脐带血标本 冈比亚是一个流行率很高的地区， 传播强度的季节性波动：（1）确定T 脐带血单个核细胞的细胞反应性不同， 妊娠并发疟疾与妊娠期间 疟疾没有发生。 分析将包括增殖性T细胞 对血液阶段抗原的反应， 血细胞或蛋白质和肽抗原; 血液阶段抗原反应性T细胞; T细胞亚群区分 通过细胞表面标记对暴露于血液阶段抗原的反应。 (2)为了评估妊娠期间感染疟疾是否会影响 脐带血单核细胞的成熟。 这一分析将包括： 研究离体单核细胞的淋巴因子谱;从 妊娠合并和未合并疟疾的脐带血;淋巴因子 在进一步用血液阶段抗原体外刺激后产生; 在相同条件下诱导细胞表面标志物。 了解这些早期反应对未来的研究至关重要 试图阐明与年龄相关的保护机制， 免疫力是疟疾疫苗开发的关键。

The patterns of malaria caused by Plasmodium falciparum are influenced by environmental factors, including endemicity and intensity of transmission. For example, children residing in hypoendemic areas commonly suffer from severe illness characterized by cerebral malaria, whereas children residing in holoendemic areas are more likely to experience parasitemia associated with severe anemia. It is quite possible that immune processes might have a profound impact upon the clinical manifestation of disease independent of the parasite density in the bloodstream. Since the placenta is a repository for blood-stage plasmodial antigens, we hypothesize that infants born to mothers who experience malaria during pregnancy develop tolerance or suppressive mechanism to blood stage antigens in utero. During subsequent malaria infections, the age-related acquisition of protective immunity is defined by the T cell repertoire that has been shaped by an early exposure to malaria antigens. We propose that the affected neonatal immune responses are reflected by the expression of characteristic phenotypic markers and immunologic functions of T cells and monocytes recoverable from cord blood cells. The following specific aims are proposed to examine these issues using cord blood specimens obtained at the time of delivery from primigravida women in The Gambia, in a region where high endemicity prevails with seasonal fluctuations in transmission intensity: (1) To determine if T cell reactivities of cord blood mononuclear cells differ between pregnancies complicated by malaria compared to pregnancies during which malaria did not occur. The analysis will include proliferative T cell responses to blood-stage antigens in the form of schizont-infected red blood cells, or protein and peptide antigens; lymphokine profiles of the blood-stage antigens-responding T cells; T cell subsets distinguished by cell surface markers in response to exposure to blood-stage antigens. (2) To evaluate if malaria infection during pregnancy affects the maturation of cord blood monocytes. This analysis will include: investigation of lymphokine profiles of ex vivo monocytes; obtained from cord blood from pregnancies with and without malaria; lymphokine production upon further in vitro stimulation with blood-stage antigens; induction of cell surface markers under the same conditions. Understanding of these early responses is essential for future studies seeking to elucidate mechanisms underlying age-related protective immunity, a pivotal point in the development of malaria vaccines.