PCB IMMUNOTOXICITY

免疫系统的主要功能是识别和 消除非自我的细胞和非细胞实体 (细菌、病毒、原生动物)或自我改变(转化的恶性细胞) 否则会危及健康。已经确定，有些人 环境污染物，包括卤代芳香族 碳氢化合物、多氯联苯和 2，3，7，8-四氯二苯并对二恶英(TCDD)，引起免疫功能障碍， 然而，这些机制尚未解决。这一领域的最新进展已经 证明TCDD和某些多氯联苯同系物的免疫毒性 是通过细胞质/核受体蛋白(芳香族 与某些卤代芳香族结合的烃(AH)受体 具有高亲和力的碳氢化合物。这一配体-Ah受体的形成 复合体导致ah基因复合体的激活，并导致 合成许多蛋白质，其中许多是酶，如芳基 碳氢羟基酶(AHH)和几种毒性作用，包括 腭裂形成，胸腺萎缩和免疫功能障碍，但 激活该复合体导致这些效应的机制 目前仍不清楚。因为已经确定了AH受体 蛋白质在淋巴组织中表达，AH受体配体可以 诱导淋巴样AHH活性，建议：1)淋巴组织 拥有功能受损的所有必要的蜂窝设备 通过激活其ah基因复合体，2)只有T的特定亚群 和B淋巴细胞对ah基因激活敏感，3)只有淋巴细胞 在分化的某些阶段对ah基因的激活很敏感， 4)淋巴组织中这种复合体的激活导致 直接或间接导致减损的产品的合成 免疫功能。这些假说将在体内和体内进行测试 毒理学和免疫学的体外方法评价几个参数 小鼠体液免疫和细胞免疫的变化 无反应，其淋巴组织已被实验性地交换 或者被迫与相反的Ah型的人合作。这些 研究将进一步阐明卤代芳烃的作用机理。 碳氢化合物与哺乳动物系统相互作用，将有助于人类 这些污染物的健康风险评估。

The primary function of the immune system is the recognition and elimination of cellular and noncellular entities which are non-self (bacteria, viruses, protozoa) or altered self (transformed malignant cells) which would otherwise compromise health. It has been established that some environmental contaminants, including the halogenated aromatic hydrocarbons, polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), cause immune dysfunction, however, the mechanisms are unresolved. Recent progress in this area has demonstrated that the immunotoxicity of TCDD and of certain PCB congeners is mediated through a cytoplasmic/nuclear receptor protein (the aromatic hydrocarbon (Ah) receptor) which binds certain halogenated aromatic hydrocarbons with high affinity. The formation of this ligand-Ah receptor complex leads to the activation of the Ah gene complex and results in the synthesis of a number of proteins, many of which are enzymes such as aryl hydrocarbon hydroxylase (AHH), and several toxic effects including cleft-palate formation, thymic atrophy, and immune dysfunction, but the mechanisms by which activation of this complex results in these effects remains unclear. Since it has been established that the Ah receptor protein is expressed in lymphoid tissue and that Ah receptor ligands can induce lymphoid AHH activity, it is proposed that: 1) lymphoid tissue possesses all the necessary cellular apparatus to be functionally impaired by activation of its Ah gene complex, 2) only specific subpopulations of T and B lymphocytes are sensitive to Ah gene activation, 3) only lymphocytes at certain stages of differentiation are sensitive to Ah gene activation, and 4) that activation of this complex in lymphoid tissue leads to the synthesis of products which directly or indirectly result in impairment of immune function. These hypotheses will be tested using in vivo and in vitro methods of toxicology and immunology to evaluate several parameters of humoral and cellular immunity in mice which are either Ah responsive or nonresponsive and whose lymphoid tissues have been experimentally exchanged or forced to cooperate with those of the opposite Ah genotype. These studies will further elucidate the mechanisms by which halogenated aromatic hydrocarbons interact with mammalian systems and will aid in the human health risk assessments of these pollutants.