MECHANISM OF METAL MEDIATED IMMUNOSUPPRESSION

描述：（改编自研究者摘要）重金属（如 如Cd、Hg、Ni、Zn、Cu和Pb）是越来越重要的污染物， 空气、水和土壤。 其中一个重要的生物系统， 暴露于重金属改变了免疫系统， 免疫能力的不适当变化可导致免疫缺陷， 自身免疫性疾病。 虽然有很多兴趣在 重金属改变免疫力的机制，仍然有许多 悬而未决的问题 在初步研究中，研究人员检查了 MT（一种小的富含半胱氨酸的金属蛋白， 重金属暴露后的细胞）可能会改变免疫活性。 金属硫蛋白可能与某些体液免疫反应有关。 与金属接触相关的免疫抑制。 比如说 研究人员发现MT抑制特异性T依赖性体液免疫反应， 反应，并且巨噬细胞功能的某些方面被MT改变。 他们还发现，在我们的研究中， 实验室可以阻断MT的某些体内免疫调节活性。 的 研究人员的发现表明，重金属暴露（或 而在其他方面，则是以减少。 由于抗原呈递细胞/辅助性T细胞免疫 交互. 体液反应的中心参数是 将评估MT抑制作用的潜在靶点。 这些 实验将建立抑制效应的机制， 发生. 具体目的是：（1）探索体内MT的动力学 与免疫系统的相互作用，并确定是否抑制 体液免疫存在于T依赖性和非依赖性应答中， (2)为了检测MT对T淋巴细胞在 调节体液免疫反应，（3）确定是否 MT改变了辅助性T细胞和巨噬细胞的相互作用，以及（4） 确定B细胞分化的模式是否被改变， MT的存在。 这项研究将有重要的意义，无论是识别 由于以下原因， 重金属接触，以及个人的诊断和治疗 暴露在过量的这些重要的环境毒素中。

DESCRIPTION: (Adapted from the Investigator's Abstract) Heavy metals (such as Cd, Hg, Ni, Zn, Cu, and Pb) are increasingly important contaminants of air, water, and soils. One of the critical biological systems which can be altered by exposure to heavy metals is the immune system, where inappropriate changes in immune capacity can result in immunodeficiency or autoimmune disease. While there is a great deal of interest in the mechanisms by which heavy metals alter immunity, there remain many unresolved issues. In preliminary studies, the investigators have examined the contributions that MT (a small, cysteine-rich metalloprotein that is rapidly induced in cells following heavy metal exposure) might make to altered immune activity. Metallothionein may be responsible for some of the forms of humoral immunosuppression associated with metal exposure. For example, the investigators have found that MT suppresses specific T-dependent humoral responses, and that some aspects of macrophage function are altered by MT. They have also found that monoclonal antibodies to MT developed in our laboratory can block some in vivo immunomodulatory activities of MT. The investigator's findings suggest that MT induced by heavy metal exposure (or indeed by exposure to other toxicants) is responsible for decreases in immunity as a consequence of antigen-presenting cell/helper T-cell interactions. The central parameters of the humoral response that are potential targets of the suppressive effect of MT will be evaluated. These experiments will establish the mechanisms by which suppressive effects occur. The Specific Aims are to: (1) explore the dynamics of in vivo MT interactions with the immune system and to determine if suppression of humoral immunity is found in both T-dependent and -independent responses, (2) to examine the effects of MT on the role that T-lymphocytes play in regulation of the humoral immune response, (3) to determine whether the interactions of helper T-cells and macrophages are altered by MT, and (4) to establish whether patterns of B-cell differentiation are altered by the presence of MT. This research will have important implications both for the identification of individuals at particular risk for immune disease as a consequence of heavy metal exposure, and for the diagnosis and treatment of individuals exposed to excessive levels of these important environmental toxins.