B CELL DEPENDENT IMMUNITY TO TOXOPLASMA GONDII

B 细胞依赖性弓形虫免疫

• 批准号: 6374379
• 负责人: Lawrence L. Johnson
• 金额: $ 38.18万
• 依托单位: TRUDEAU INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6374379
• 关键词: B lymphocyte; SCID mouse; Toxoplasma gondii; antibody formation; antibody receptor; antigen antibody reaction; cellular immunity; cytokine; enzyme linked immunosorbent assay; flow cytometry; immunopathology; laboratory mouse; passive immunization; pathologic process; polymerase chain reaction; protozoal infection; statistics /biometry; virulence

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 reasearch 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 ability of immune serum, together with immune T cells, to confer protection against a challenge infection with virulent tachyzoites will be addressed in adoptive immunization experiments. The resistance of vaccinated mice with mutated Fc receptor genes or C3, C4, or C5 complement genes will be examined in relation to the hypothesis that antibodies are essential to protection in this model. The potential for B cells to regulate cytokine production and the generation of T. gondii-specific T cells 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细胞及其产物在小鼠中抗弓形虫感染中的作用。弓形虫病是艾滋病患者和先天感染个体发病率/死亡率的重要原因，也是一种重要的重新研究工具，可以分析宿主对致病微生物的抗药性的先天和获得的免疫学机制。 B细胞缺陷型MUMT小鼠的感染表明，需要B细胞，以使小鼠抵抗慢性原发性T. gondii感染，并在先前接种疫苗的情况下以高毒性寄生虫的挑战来生存。 提出了两个假设来解释B细胞在抗T. gondii抗性中的作用。 提出的实验将检查是否需要B细胞来生产保护性抗体，还是调节T. gondii诱导的T细胞和有可能引起免疫病理学的细胞因子的细胞因子。通过分析受感染的MUMT和对照B细胞充足的小鼠的宿主细胞和细胞因子反应以及组织病理学的分析，将解决实验目标。 免疫血清以及免疫T细胞的能力将在收养免疫实验中介绍防止挑战感染的挑战感染。 通过突变的FC受体基因或C3，C4或C5补体基因的抗性小鼠的耐药性将与以下假说有关，即在该模型中抗体对于保护至关重要。 将研究B细胞调节细胞因子产生和T. gondii特异性T细胞的产生的潜力。 同样，将分析B细胞在预防先天性T. gondii感染的保护中的作用以及弓形虫特异性抗体对感染为新生儿的小鼠抗性的影响。