Analysis of Trypanosome-Evoked Depression of Immunity

锥虫引起的免疫抑制分析

• 批准号: 8803032
• 负责人: Julia Albright
• 金额: $ 14.75万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1992-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8803032&HistoricalAwards=false
• 关键词: Analysis; Trypanosome; Evoked; Depression; Immunity

Trypanosomes, like many protozoan parasites, are unable to synthesize purines and must rely on the host to provide those compounds. The demand placed on the host's pool of free purines by a rapidly-growing population of extracellular, bloodstream trypanosomes (such as the rodent or African trypanosomes) may have one of two effects, either: (a) marked mobilizaton of purines from tissue sites into the bloodstream, or (b) serious depletion of the normal, circulating concentrations of purines. In either case, the available evidence suggests that significant alterations of the normal properties and functions of host cells that display surface adenosine receptors would result (especially lymphocytes, neutrophils, macrophages and platelets). The goals of this research are to investigate changes in bloodstream purine concentrations and changes in the properties and functions of selected host cells during the course of murine infections with Trypanosoma musculi. The concentrations of 16 purines in the plasma will be determined (by high performance liquid chromatography) at intervals during the course of infection, and subsequent recovery, of two strains of mice (one, C3H, that is particularly susceptible to T. musculi and another, C57Bl/6, that is considerably less susceptible). The marked (3-5 fold) rise in splenocyte activity of the enzymes, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP), which recently has been discovered in trypanosome-infected mice will be studied in detail. Specifically it will be determined: (a) whether or not the stimulation of these enzymes results from an excess or a paucity of purines in the bloodstream, (b) which types of splenic cells display the elevated enzyme activities, (c) whether or not the stimulus comes from direct action of the parasites (or parasite-derived substances) on cells in which the enzyme activity increases or is mediated indirectly through another type of host cell, and (d) whether or not the elevated enzyme levels are associated with depressed capability of infected hosts to generate immune responses. Finally, once it is known how the bloodstream concentrations of purines change during infection, the effects of similar changes in the properties and functions of selected cells (B-lymphocytes, T-lymphocytes, neutrophils, Kupffer cells and platelets) maintained in vitro will be explored. These studies will provide insight concerning the mechanisms through which trypanosome-mediated alterations in host purine concentrations result in altered cellular activities, and may help to explain the success of trypanosomes in resisting the immune responses of their hosts.

锥虫，像许多原生动物寄生虫一样， 合成嘌呤，必须依靠宿主提供这些嘌呤， 化合物. 对宿主游离嘌呤库的需求 由快速增长的细胞外血液 锥虫（如啮齿动物或非洲锥虫）可 有两个效果之一，要么：（a）显着动员 嘌呤从组织部位进入血液，或（B）严重 嘌呤的正常循环浓度的消耗。 在这两种情况下，现有的证据表明， 宿主细胞正常特性和功能的改变 显示表面腺苷受体会导致（特别是 淋巴细胞、嗜中性粒细胞、巨噬细胞和血小板）。 的目标 这项研究的目的是研究血液中嘌呤的变化， 浓度和变化的性质和功能 选择的宿主细胞在鼠感染过程中， 肌肉锥虫 16种嘌呤的浓度 等离子体将被测定（通过高性能液体 在感染过程期间间隔地进行层析），以及 随后的恢复，两个品系的小鼠（一个，C3 H，即 特别是对T. musculi和另一个，C57 Bl/6， 不太容易受影响）。 显着上升（3-5倍） 酶、腺苷脱氨酶（ADA）和 嘌呤核苷磷酸化酶（PNP），最近已被 在锥虫感染的小鼠中发现的， 详细 具体而言，将确定：（a）是否 这些酶的刺激是由于过量或 血液中嘌呤缺乏，（B）哪种类型的脾 细胞显示升高的酶活性，（c）是否 刺激来自寄生虫的直接作用（或 寄生虫衍生的物质）在细胞中的酶 活动增加或间接通过另一种类型介导 （d）宿主细胞的酶水平是否升高， 与受感染宿主的能力降低有关， 产生免疫反应。 最后，一旦知道了 嘌呤的血流浓度在感染期间改变， 的性质和功能的类似变化的影响， 选择的细胞（B淋巴细胞，T淋巴细胞，嗜中性粒细胞， Kupffer细胞和血小板）将在体外维持。 探讨了 这些研究将提供有关机制的见解 通过锥虫介导的宿主嘌呤 浓度导致细胞活动改变， 有助于解释锥虫成功抵抗 宿主的免疫反应。