Berczi I, Chow D A, Sabbadini E R
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Domest Anim Endocrinol. 1998 Sep;15(5):273-81. doi: 10.1016/s0739-7240(98)00015-0.
The development and function of the immune system is regulated by neuroendocrine factors. Immune function may be divided into adaptive and natural immunity. Adaptive immune responses are driven by specific determinants of the antigen (epitopes), require 5-10 d to fully develop, and show an accelerated or memory response after repeated exposure to the same antigen. Natural immunity may be divided into host defense mediated by non-immune factors (e.g., antimicrobial proteins, enzymes, mucus etc.) and polyspecific responses of the immune system. This polyspecific response relies on natural antibodies and on some other serum proteins (e.g., lipopolysaccharide-binding protein-LBP, C-reactive protein-CRP), and on surface receptors of macrophages, natural killer cells and B and T lymphocytes for activation. Highly conserved homologous (crossreactive) epitopes, or homotopes for short, are recognized by the natural immune system. Natural antibodies, LBP, and CRP are capable of activating the entire immune system after combination with the appropriate homotope. During febrile illness natural immune host defense is promptly elevated because of the rapid rise of natural antibodies, LBP, and CRP in the serum. This is known as the acute phase response (APR), which is initiated by a sudden rise of cytokines in the circulation, such as IL-1, IL-6, and TNF-alpha. The cytokines act on the brain, the neuroendocrine system, and on other tissues and organs, which leads to fever and profound hormonal and metabolic changes. The hypothalamus-pituitary adrenal axis is activated and serves as the primary regulator of immune and inflammatory reactions. Insulin, glucagon, and catecholeamine levels are also raised. Bone marrow activity and leukocyte function are high and the liver is converted to the rapid production of acute-phase proteins (APP). APP include LBP, CRP, fibrinogen, some complement components, enzyme inhibitors, and anti-inflammatory proteins, which may rise in the serum from several hundred to a thousand times within 24-48 hr. Therefore, natural immunity is a polyspecific response to homotopes, which functions as an instantaneous defense mechanism in health and which is rapidly boosted by cytokines and hormones during febrile illness. This is a highly successful defense reaction, as in the overwhelming majority of cases, febrile illness leads to recovery and the development of adaptive immunity in man and higher animals.
免疫系统的发育和功能受神经内分泌因子调节。免疫功能可分为适应性免疫和天然免疫。适应性免疫反应由抗原的特定决定簇（表位）驱动，需要5 - 10天才能充分发展，并且在重复接触相同抗原后会出现加速或记忆反应。天然免疫可分为由非免疫因子介导的宿主防御（如抗菌蛋白、酶、黏液等）以及免疫系统的多特异性反应。这种多特异性反应依赖于天然抗体和一些其他血清蛋白（如脂多糖结合蛋白-LBP、C反应蛋白-CRP），以及巨噬细胞、自然杀伤细胞和B及T淋巴细胞的表面受体来激活。高度保守的同源（交叉反应）表位，简称为同型表位，可被天然免疫系统识别。天然抗体、LBP和CRP在与适当的同型表位结合后能够激活整个免疫系统。在发热性疾病期间，由于血清中天然抗体、LBP和CRP的迅速升高，天然免疫宿主防御会迅速增强。这被称为急性期反应（APR），它由循环中细胞因子如IL-1、IL-6和TNF-α的突然升高引发。这些细胞因子作用于大脑、神经内分泌系统以及其他组织和器官，导致发热以及深刻的激素和代谢变化。下丘脑-垂体-肾上腺轴被激活，并作为免疫和炎症反应的主要调节者。胰岛素、胰高血糖素和儿茶酚胺水平也会升高。骨髓活性和白细胞功能增强，肝脏转变为快速产生急性期蛋白（APP）。APP包括LBP、CRP、纤维蛋白原、一些补体成分、酶抑制剂和抗炎蛋白，它们在血清中的水平可在24 - 48小时内从几百倍升高到一千倍。因此，天然免疫是对同型表位的多特异性反应，它在健康状态下作为一种即时防御机制发挥作用，并且在发热性疾病期间会被细胞因子和激素迅速增强。这是一种非常成功的防御反应，因为在绝大多数情况下，发热性疾病会导致人类和高等动物康复并产生适应性免疫。
