Developmental immunotoxicology (DIT): windows of vulnerability, immune dysfunction and safety assessment
Developmental immunotoxicology (DIT): windows of vulnerability, immune dysfunction and safety assessment
复制标题
DOI：
10.1080/15476910802483324
复制
发表时间：
2008-10-01
影响因子：
3.3
通讯作者：
Dietert, Rodney R.
中科院分区：
文献类型：
--
作者：
Dietert, Rodney R.
发育性免疫毒性（DIT）是一个日益增长的健康问题，因为DIT结果使儿童易患近几十年来一直在上升的那些疾病（例如，儿童哮喘、过敏性疾病、自身免疫性疾病、儿童感染）。发育中的免疫系统对环境伤害的脆弱性增强是基于在生命早期脆弱性的关键窗口期间发生的独特免疫成熟事件。半同种异体妊娠状态，抑制移植物排斥反应和相关的胎儿和新生儿免疫系统的偏斜，也影响DIT结果的特定性质。在暴露的后代中，靶向免疫抑制可以与过敏性和/或自身免疫性疾病的风险增加共存。由于与DIT免疫功能障碍，而不是深刻的免疫抑制是更大的关注，测试方法应强调多功能评估。除了T细胞，树突细胞和巨噬细胞也是敏感的靶点。最后三个月的胎儿和新生儿通常在TH 1依赖性功能和出生后获得所需的TH 1能力是一个主要的关注与DIT。考虑到这一点，评估应包括测量TH 1依赖性细胞介导的免疫[细胞毒性T淋巴细胞（CTL）活性或迟发型超敏反应（DTH）反应]，以及多同种型T依赖性抗体反应（TDAR）和先天免疫（例如，NK活性）。其他参数，如免疫组织学、免疫表型、细胞因子反应和器官重量，在纳入免疫功能评价时可能有用。一个多功能的DIT协议使用流感的挑战，作为一个例子，允许功能障碍和失调的方法进行评估。
Developmental immunotoxicity (DIT) is an increasing health concern since DIT outcomes predispose children to those diseases that have been on the rise in recent decades (e.g., childhood asthma, allergic diseases, autoimmune conditions, childhood infections). The enhanced vulnerability of the developing immune system for environmental insult is based on unique immune maturational events that occur during critical windows of vulnerability in early life. The semi-allogeneic pregnancy state, with suppression of graft rejection and associated skewing of the fetal and neonatal immune system, also influences the specific nature of DIT outcomes. In the exposed offspring, targeted immunosuppression can co-exist with an increased risk of allergic and/or autoimmune disease. Because with DIT immune dysfunction rather than profound immunosuppression is the greater concern, testing approaches should emphasize multi-functional assessment. Beyond T-cells, dendritic cells and macrophages are sensitive targets. The last-trimester fetus and the neonate are normally depressed in TH1-dependent functions and postnatal acquisition of needed TH1 capacity is a major concern with DIT. With this in mind, assessment should include a measure of TH1-dependent cell-mediated immunity [cytotoxic T-lymphocyte (CTL) activity or delayed-type hypersensitivity (DTH) response] in conjunction with a multi-isotype T-dependent antibody response (TDAR) and evaluation of innate immunity (e.g., NK activity). Other parameters such as immune histology, immunophenotyping, cytokine responses, and organ weights can be useful when included with immune functional evaluation. A multifunctional DIT protocol using influenza challenge is presented as one example of an approach that permits dysfunction and misregulation to be evaluated.