AGENTS TO INDUCE IMMUNOTOXICITY

建立该接触是为了评价环境因子、治疗药物或生物材料在啮齿动物模型中诱导免疫毒性、超敏反应改变或自身免疫性疾病的可能性。 这是通过三种机制实现的。 第一种机制是使用一组定义和验证的免疫功能试验、宿主抗性模型和啮齿动物超敏反应试验，检查供试化学品调节免疫应答的能力。 这些研究将评估人类接触的潜在危害，并增加关于影响免疫系统的化学品数量的数据库。 第二个目标是开发和验证新的方法，并利用分子生物学和毒理学领域的进步，以提高用于评估免疫毒性的标准化测试组的预测价值。 这些新发展的例子包括使用RNA酶保护测定来建立化学刺激物和致敏物的细胞因子谱。 最后，根据该合同进行的研究将解决观察到的免疫功能改变的潜在细胞和分子基础。 分子技术，如RT-PCR，细胞活化标志物的分析和靶细胞亚群的评价将有助于阐明免疫毒性剂的特定细胞靶点，并提出潜在的策略，以尽量减少对人类的风险。

This contact was established to evaluate the potential for environmental agents, therapeutic drugs or biological materials to induce immunotoxicity, altered hypersensitivity responses or autoimmune disease in rodent models. This is accomplished via three mechanisms. The first mechanism is to examine the ability of test chemical to modulate immune responses using a defined and validated panel of immune function tests, host resistance models and hypersensitivity assays in rodents. These studies will provide assessment of the potential hazards of human exposure and increase the database regarding the number of chemicals which affect the immune system. A second objective is to develop and validate new methodologies and make use of advancements in the fields of molecular biology and toxicology, to increase the predictive value of the standardized testing panels used to evaluate immunotoxicity. Examples of such new developments include the use of the RNAse protection assay to establish cytokine profiles for chemical irritants and sensitizers. Finally, studies conducted under this contract will address the underlying cellular and molecular basis for observed alterations in immune functions. Molecular techniques such as RT-PCR, analysis of cell activation markers and evaluation of targeted cell subpopulations will help elucidate the specific cellular targets of immunotoxic agents and suggest potential strategies for minimizing risks to the human population.