B CELLS AND RESPONSE TO T GONDII

B 细胞和对弓形虫的反应

• 批准号: 2839684
• 负责人: Lawrence L. Johnson
• 金额: $ 34.7万
• 依托单位: TRUDEAU INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2839684
• 关键词: B lymphocyte; SCID mouse; Toxoplasma gondii; antibody receptor; antigen antibody reaction; cell cell interaction; cellular immunity; cytokine; cytotoxic T lymphocyte; embryo /fetus; enzyme linked immunosorbent assay; flow cytometry; genetically modified animals; histopathology; immunopathology; intracellular parasitism; laboratory mouse; leukocyte activation /transformation; newborn animals; placental transfer; polymerase chain reaction; protozoal vaccine; toxoplasmosis; vector vaccine

The proposed research will analyze the role of B cells and their products in resistance to Toxoplasma gondii infection in mice. Toxoplasmosis is a significant cause of morbidity/mortality in AIDS patients and congenitally infected individuals, and is also an important research tool with which to analyze innate and acquired immunological mechanisms of host resistance to pathogenic microbes. Infection of B cell-deficient muMT mice has revealed that B cells are needed in order for mice to resist chronic primary T. gondii infection and to survive challenge with highly virulent parasites if previously vaccinated. Two hypotheses are proposed to explain the role of B cells in resistance to T gondii. The proposed experiments will examine whether B cells are needed for the production of protective antibodies or for the regulation of T. gondii-induced T cells and cytokines having the potential to cause immunopathology. Experimental goals will be addressed by analysis of host cell and cytokine responses and histopathology in infected muMT and control B cell-sufficient mice. The resistance of vaccinated mice with mutated Fc receptor genes or C3 and C4 complement genes will be examined in relation to the hypothesis that antibodies are essential to protection in this model. We will also determine the extent of protection afforded by a DNA vaccine that encodes a major surface protein of T. gondii tachyzoites and elicits antibodies against this protein. The potential for B cells to regulate cytokine production and the generation of T. gondii-specific CTL will be studied. Also, the role of B cells in protection against congenital T. gondii infection and the influence of Toxoplasma-specific antibodies on the resistance of mice infected as neonates will be analyzed.

拟议的研究将分析B细胞及其其作用 对小鼠的抗毒素贡二感染的抗性产物。 弓形虫病是艾滋病发病率/死亡率的重要原因 患者和先天感染的个体，也是重要的 研究工具可以分析先天和获得的免疫学 宿主对致病微生物的抗性机制。 感染b 缺乏细胞的MUMT小鼠已经表明需要B细胞 使小鼠抵抗慢性原发性T. gondii感染并生存 如果先前接种疫苗，则应使用高毒性寄生虫进行挑战。 二 提出了假设来解释B细胞在抗性中的作用 T Gondii。 提出的实验将检查B细胞是否是 生产保护性抗体或法规所需的 T. gondii诱导的T细胞和具有引起潜力的细胞因子 免疫病理学。实验目标将通过分析 受感染的MUMT和 控制B足够的小鼠。 接种小鼠的抗性 将检查突变的FC受体基因或C3和C4补体基因 关于抗体对于 在此模型中保护。 我们还将确定 由编码主要表面的DNA疫苗提供的保护 T. gondii tachyzoites的蛋白质和对此引起抗体的抗体 蛋白质。 B细胞调节细胞因子产生的潜力和 将研究T. gondii特异性CTL的产生。 另外， B细胞在防止先天性T. gondii感染和 弓形虫特异性抗体对 将分析被感染为新生儿的小鼠。