Neuroimmunotoxicology: autoimmunity, viral, infectious a

由于NIEHS各研究人员对多学科的兴趣，该项目于今年启动。在过去的几年里，免疫系统和神经系统之间的相互作用虽然还没有被理解，但已经得到了很好的证实。这些相互作用可能是直接的，间接的，通过下丘脑-垂体-肾上腺轴或通过大脑的常驻免疫细胞。免疫系统和神经系统（以及可能与生殖系统的相互作用）之间存在许多联系，包括：1)两个系统在出生后发育/成熟的时间延长。2)妊娠母亲的感染和可能的感染转移给后代或促炎级联因子（TNFalpha, Interleukin-6）转移给后代以及与免疫介导反应相关的对儿童的长期影响。3)活性病毒转移到大脑（如疱疹、艾滋病毒、西尼罗河病毒），并表现为认知缺陷/痴呆。4)与自身免疫性疾病（如艾滋病、多发性硬化症、色氨酸诱导的自身免疫）相关的人类病例中认知缺陷的发生率增加；5)使用抗炎药物治疗认知障碍的干预缺乏成功，这表明系统之间的相互作用比先前预期的更复杂。在接触环境因素的框架内，存在大量的数据基础，表明免疫系统的急性反应可能由于接触化学物质而发生。NIEHS正在进行额外的努力，以获得有关免疫系统发育的信息。通常，有能力改变免疫系统的药物或因素也会改变神经系统。因此，本项目的目的是试图确定这两个系统之间的相互作用，这些相互作用不仅可能导致急性不良反应，而且可能导致长期不良后果。

This project was initiated this year due to the multidisciplinary interest of various investigators at NIEHS. Over the last few years, interactions between the immune system and the nervous system have become well established if not yet understood. These interactions may be direct, indirect, via the Hypothalamic-Pituitary-Adrenal Axis or vis the resident immune cells of the brain. There have been a number of proposed links between the immune system and the nervous system (and possible interactions with the reproductive system) including: 1) prolonged post-natal development/maturation of both systems. 2) infection in the pregnant mother and possible transfer of infection to the offspring or the transfer of factors of the pro-inflammatory cascade (TNFalpha, Interleukin-6) to the offspring and long-term effects on the child as related to an immune-mediated response. 3) the transfer of active virsus into the brain (e.g., Herpes, HIV, West-Nile) and the manifestation of cognitive deficits/dementia. 4) the increased occurrance of cognitive deficits in human cases related to autoimmune disease (e.g., AIDs, Multiple Sclerosis, Tryptophan-induced autoimmunity), 5) the lack of success with therapeutic intervention with anti-inflammatory agents for cognitive impairment suggesting a more complicated interactions between the systems than previously anticipated. Within the framework of exposure to environmental agents, there exists a substantial data base to suggest that acute responses of the immune system can occur as a result of chemical exposure. Additional efforts are underway within NIEHS to generate such information of the developing immune system. Quite often, the agents or factors that have the capacity to alter the immune system are shown to also alter the nervous system. Thus, it is the purpose of this project to attempt to identify interactions between the two systems that may contribute not only to acute adverse effects but also to long-term adverse outcomes.