Bellinger Denise L, Lubahn Cheri, Lorton Dianne
Department of Human Anatomy and Pathology, Loma Linda University School of Medicine, Loma Linda, CA 92352, USA.
J Immunotoxicol. 2008 Oct;5(4):419-44. doi: 10.1080/15476910802483415.
Stress is triggered by a variety of unexpected environmental stimuli, such as aggressive behavior, fear, forced physical activity, sudden environmental changes, social isolation or pathological conditions. Stressful experiences during very early life (particularly, maternal stress during fetal ontogeny) can permanently alter the responsiveness of the nervous system, an effect called programming or imprinting. Programming affects the hypothalamic-pituitary-adrenocortical (HPA) axis, brain neurotransmitter systems, sympathetic nervous system (SNS), and the cognitive abilities of the offspring, which can alter neural regulation of immune function. Prenatal or early life stress may contribute to the maladaptive immune responses to stress that occur later in life. This review focuses on the effect of maternal and early life stress on immune function in the offspring across life span. It highlights potential mechanisms by which prenatal stress impacts immune functions over life span. The literature discussed in this review suggests that psychosocial stress during pre- and early postnatal life may increase the vulnerability of infants to the effects of immunotoxicants or immune-mediated diseases, with long-term consequences. Neural-immune interactions may provide an indirect route through which immunotoxicants affect the developing immune system. A developmental approach to understanding how immunotoxicants interact with maternal and early life stress-induced changes in immunity is needed, because as the body changes physiologically across life span so do the effects of stress and immunotoxicants. In early and late life, the immune system is more vulnerable to the effects of stress. Stress can mimic the effects of aging and exacerbate age-related changes in immune function. This is important because immune dysregulation in the elderly is more frequently and seriously associated with clinical impairment and death. Aging, exposure to teratogens, and psychological stress interact to increase vulnerability and put the elderly at the greatest risk for disease.
压力是由各种意外的环境刺激引发的，如攻击行为、恐惧、强迫性身体活动、突然的环境变化、社会隔离或病理状况。生命早期的应激经历（特别是胎儿发育过程中母亲的应激）可永久性改变神经系统的反应性，这种效应称为编程或印记。编程会影响下丘脑 - 垂体 - 肾上腺皮质（HPA）轴、脑内神经递质系统、交感神经系统（SNS）以及后代的认知能力，进而改变免疫功能的神经调节。产前或生命早期的应激可能导致日后生活中对应激的适应不良免疫反应。本综述重点关注母亲和生命早期应激对后代整个生命周期免疫功能的影响。它强调了产前应激在整个生命周期中影响免疫功能的潜在机制。本综述中讨论的文献表明，产前和产后早期的心理社会应激可能会增加婴儿对免疫毒物或免疫介导疾病影响的易感性，并产生长期后果。神经 - 免疫相互作用可能提供了一条间接途径，通过这条途径免疫毒物影响发育中的免疫系统。需要一种发育学方法来理解免疫毒物如何与母亲和生命早期应激诱导的免疫变化相互作用，因为随着身体在整个生命周期中发生生理变化，应激和免疫毒物的影响也会发生变化。在生命早期和晚期，免疫系统更容易受到应激的影响。应激可模拟衰老的影响并加剧与年龄相关的免疫功能变化。这很重要，因为老年人的免疫失调更频繁、更严重地与临床损伤和死亡相关。衰老、接触致畸物和心理应激相互作用，增加了易感性，使老年人面临最大的疾病风险。
