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IMMUNOGENETICS OF TRICHINELLA SPIRALIS

旋毛虫的免疫遗传学

基本信息

批准号：
3137355
负责人：
DONALD WASSOM
金额：
$ 17.01万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 1992-06-30
项目状态：
已结题

项目摘要

Mice which express H-2 encoded I-E molecules are more susceptible to T. spiralis infection than mice which do not. Two additional H-2 genes and a gene on chromosome 4 are also known to influence the anti-Trichinella response. Experiments are proposed to compare the phenotypically expressed cellular and humoral anti-parasite responses regulated by each of the genes identified. For studies on the cellular and molecular mechanisms which underly the association between I-E expression and susceptibility to infection, transgenic mice which express I-E will be constructed by inserting the E alpha gene into I-E-negative mice which possess a functional gene at E beta. H-2 congenic strains of mice and selected offspring from matings between these strains will be studied to determine if certain I-E alleles are associated with susceptibility to infection while others are not. In addition, Fv-1 congenic strains of mice and offspring from crosses between them will be studied to more precisely map the gene on chromosome 4 which influences the anti-Trichinella responses, and to determine if the gene controlling I-J expression cosegregates with the gene controlling susceptibility to T. spiralis infection. A recently developed assay to enumerate parasite- specific antibody secreting cells will be used, along with populations of cloned, T. spiralis-specific T cells, to identify and characterize I-J positive, Trichinella-specific suppressor T cells, and to determine if autoreactive T cells with regulatory functions arise during the course of a T. spiralis infection. Functional antigens from different development stages of the parasite will be characterized using serum from susceptible and resistant mouse strains to precipitate antigens from soluble worm extracts. Monoclonal antibodies will be used to affinity purify relevant antigens from these preparations. Regulation of the immune response to protective antigens, purified to homogeneity, will be compared in susceptible and resistant strains in mice. The long range goal of this project is to determine how immune regulation differs in susceptible and resistant strains of hosts.

表达H-2编码的I-E分子的小鼠对T.螺旋感染的小鼠比没有螺旋感染的小鼠多。两另外的H-2基因和4号染色体上的基因也是已知的来影响抗旋毛虫反应实验建议比较表型表达的细胞和由每个基因调节的体液抗寄生虫反应鉴定用于细胞和分子机制的研究这是I-E表达与感染的易感性，表达I-E的转基因小鼠将通过将E α基因插入I-E阴性的具有功能性E β基因的小鼠。 H-2同源小鼠品系和从交配中选择的后代将研究这些菌株以确定某些I-E等位基因是否与感染易感性相关而另一些则不相关。在此外，Fv-1同源小鼠品系和杂交后代将研究它们之间的关系，以更精确地绘制基因图谱影响抗旋毛虫反应的4号染色体，并确定控制I-J表达的基因与控制对T.旋毛虫感染最近开发的寄生虫计数方法- 将使用特异性抗体分泌细胞，沿着克隆群体，T.螺旋体特异性T细胞，以识别和表征I-J阳性旋毛虫特异性抑制性T细胞，并确定具有调节功能的自身反应性T细胞在T的过程中出现。螺旋体感染功能来自寄生虫不同发育阶段的抗原将被用敏感和抗性小鼠的血清表征菌株从可溶性蠕虫提取物中沉淀抗原。单克隆抗体将用于亲和纯化相关的从这些制剂中提取抗原。调节免疫对纯化至同质的保护性抗原的反应，在小鼠中比较敏感和耐药菌株。长这个项目的目标是确定免疫调节在宿主的敏感和抗性菌株上有所不同。