树突状细胞与相关激素的基础研究

内分泌系统和免疫系统之间的联系是近十几年来的研究热点。研究显示，淋巴细胞膜表面有多种神经递质受体及激素受体，提示神经内分泌系统通过其递质或激素和淋巴细胞膜表面受体结合，介导免疫系统的调节。另外，神经内分泌细胞膜上有免疫反应产物如白细胞介素（IL-1、IL-2、IL-3、IL-6等）、胸腺肽等细胞因子的受体，免疫系统也可通过细胞因子对神经内分泌系统的功能发生影响，甚至产生免疫反应性激素，如ACTH、TSH、HCG、生长激素等．     

精神神经免疫学的兴起及其研究进展

神经内分泌系统与免疫系统之间存在双向信息传递机制，即免疫系统不仅受神经、内分泌系统的调控，而且还能调节神经、内分泌系统的某些功能。这种相互作用的功能联系是通过神经、内分泌和免疫三大调节系统共有的化学信息分子与受体实现的。即：免疫系统不仅具有多种神经内分泌激素的受体，还能合成各种免疫神弱递质和内分泌激素，并其发生反应；免疫系统产生的单核细胞因子能影响中枢神经系统（ＣＮＳ），ＣＮＳ又能合成细胞因子及其     

IL-10 对脑内免疫平衡的调控作用及机制的进展

炎症是宿主抵御病原体入侵、感染和损伤的关键,但过度的炎症反应也对机体造成损伤。过度的炎症反应是神经退行性疾病等多种疾病发生发展的重要原因,而免疫系统则形成多种监控机制抵抗炎症反应。IL-10作为一种抗炎细胞因子,能从多个环节影响机体免疫反应。本文从中枢神经系统中IL-10生成的分子机制及其对免疫反应的调节机制等方面展开讨论,阐述IL-10在神经退行性疾病中的作用。     

神经系统和免疫系统间的相互作用

神经系统可协调和综合机体内各种细胞,组织及器官的活动,因此,神经系统和免疫系统间存在功能联系是不足为奇的。早在本世纪初,就有学者发现下丘脑具有免疫调节作用。此后,关于神经系统、内分泌系统和免疫系统之间相互联系、相互作用的文章陆续发表。近十余年来,这方面的研究日益受到重视,进展较快,已形成了神经免疫学这门新的学科。神经系统和免疫系统间的相互作用,即神经系统调节免疫系统的功能,而免疫系统影响神经系统的活动,它们以神经递质和内分泌激素为媒介。本文就以     

神经系统与免疫系统

<正> 神经系统与免疫系统都是调整机体内外环境稳定,免遭损害的功能系统,两者在许多方面有共同性、特殊性和相互调节的特性。神经系统与免疫系统的共同性从神经解剖角度来看,神经系统包括中     

神经-内分泌-免疫调节网络与疾病

近年来对神经 -内分泌系统和免疫系统之间相互作用、相互依赖的复杂关系的研究已经成为一门独立的边缘学科 ,即神经免疫调节 (ｎｅｕｒｏｉｍ ｍｕｎｏｒｅｇｕｌａｔｉｏｎ)或神经免疫内分泌学[1 ] (ｎｅｕｒｏ -ｉｍ ｍｕｎｏ -ｅｎｄｏｃｒｉｎｏｌｏｇｙ)。研究者们已通过大量实验证实 ,神经系统通过其广泛的外周神经突触及其分泌的神经递质和众多的内分泌激素[2 ] ,甚至还有神经细胞分泌的细胞因子[3] ,来共同调控着免疫系统的功能 ;而免疫系统通过免疫细胞产生的多种细胞因子和激素样物质反馈作用于神经内分泌系统[4] 。两个系统的细…     

精神神经免疫学的兴起及其研究进展

神经内分泌系统与免疫系统之间存在双向信息传递机制，即免疫系统不仅受神经、内分泌系统的调控，而且还能调节神经、内分泌系统的某些功能。这种相互作用的功能联系是通过种经、内分泌和免疫三大调节系统共有的化学信息分子与受体实现的。即：免疫系统不仅具有多种神经内分泌激素的受体，还能合成各种免疫神经递质和内分泌激素，并对其发生反应：免疫系统产生的单核细胞因子能影响中枢神经系统（ＣＮＳ），ＣＮＳ又能合成细胞因子及其受体，且对其发生反应。     

IL-35研究进展

细胞因子在介导机体针对病原微生物的免疫反应、自身免疫耐受以及维持机体内环境平衡等过程中起了重要作用,IL-35是最近几年新发现的细胞因子,属于IL-12细胞因子家族,对免疫系统和免疫反应有负向抑制作用。本文对这一新细胞因子生物学特性的研究现状作一综述。     

IL-1β通过加重脂质诱导的内质网应激导致人系膜细胞损伤

 目的： 探讨白细胞介素1β（IL-1β）加重脂质诱导的内质网应激（ERS）而导致人肾小球系膜细胞（HMCs）损伤的分子机制。方法：将HMCs分为对照组、高脂组（LDL）、IL-1β+高脂组（IL-1β+LDL）及4-苯基丁酸(4-PBA)干预组（4-PBA+IL-1β+LDL）。油红O染色检测HMCs胞内脂质沉积;real-time PCR检测葡萄糖调节蛋白78(GRP78)、蛋白激酶R样内质网激酶（PERK）和α-平滑肌肌动蛋白（α-SMA） mRNA水平;免疫细胞化学分析GRP78蛋白水平; Western blotting检测NF-κB p65水平;ELISA法测定细胞培养上清IL-6和TGF-β1含量。结果：与LDL组相比,IL-1β+LDL组胞内脂质沉积、GRP78 mRNA与蛋白水平、PERK mRNA水平、NF-κB p65水平及IL-6分泌量均显著增高（均P＜0.05）;4-PBA可减少胞内脂质沉积,降低GRP78 mRNA与蛋白及PERK mRNA水平,抑制NF-κB p65的表达,减少IL-6的分泌（均P＜0.05 vs IL-1β+LDL组）。与LDL组相比,IL-1β+LDL组α-SMA mRNA表达增高（P＜0.05）,4-PBA可显著降低其表达（P＜0.05 vs IL-1β+LDL组）。结论：IL-1β可加重脂质诱导的ERS,从而导致细胞损伤。     

醋酸舍莫瑞林拮抗环磷酰胺免疫抑制作用的实验研究

醋酸舍莫瑞林 (sermorelinacetate, SA)是人工合成的由29个氨基酸组成的生长激素释放素, 为内源性促生长激素释放激素(GHRH)的氨基末端片段, 具有显著的调节生长的效应 [1, 2], 其相对分子质量 (Mr)为 3 358. 03。Blacklock等 [3]提出, 神经肽 /神经递质、激素及细胞因子是神经系统、内分泌系统及免疫系统三大系统间相互调节的共用介质。免疫系统除本身非常精细的调节机制外, 还受到神经 内分泌 免疫网络的调节。我们观察了SA对环磷酰胺 (Cyclophosphamide,CY)所致免疫抑制作用的影响, 探讨了SA对机体细胞免疫功能的调节作用。1…     

Enteric neuroimmune interactions coordinate intestinal responses in health and disease

The enteric nervous system (ENS) of the gastrointestinal (GI) tract interacts with the local immune system bidirectionally. Recent publications have demonstrated that such interactions can maintain normal GI functions during homeostasis and contribute to pathological symptoms during infection and inflammation. Infection can also induce long-term changes of the ENS resulting in the development of post-infectious GI disturbances. In this review, we discuss how the ENS can regulate and be regulated by immune responses and how such interactions control whole tissue physiology. We also address the requirements for the proper regeneration of the ENS and restoration of GI function following the resolution of infection.     

It takes nerve to tell T and B cells what to do

The existence of an association between the brain and immunity has been documented. Data show that the nervous and immune systems communicate with one another to maintain immune homeostasis. Activated immune cells secrete cytokines that influence central nervous system activity, which in turn, activates output through the peripheral nervous system to regulate the level of immune cell activity and the subsequent magnitude of an immune response. In this review, we will focus our presentation and discussion on the findings that indicate a regulatory role for the peripheral sympathetic nervous system in modulating the level of cytokine and antibody produced during an immune response. Data will be discussed from studies involving the stimulation of the beta2 adrenergic receptor expressed on CD4+ T cells and B cells by norepinephrine or selective agonists. We will also discuss how dysregulation of this line of communication between the nervous and immune systems might contribute to disease development and progression.     

T淋巴细胞与肝移植免疫耐受

背景：肝移植排斥反应的发病机制主要是T细胞介导的免疫应答,具有调节细胞功能的高活性、多功能的低分子蛋白质即细胞因子在器官移植排斥反应和免疫耐受中发挥着重要作用。目的：就T淋巴细胞与肝移植后免疫耐受的关系及研究现状作一综述。方法：由第一作者检索Medline 数据库及维普医学数据库1995年1月至2013年6月有关肝移植后免疫状态与T淋巴细胞及其细胞因子作用的文献。以“liver transplantation, immune tolerance, rejection, T lymphocytes”为英文检索词,“肝移植,排斥反应,免疫耐受,T淋巴细胞”为中文检索词,排除重复研究类文章。选取相关文献查找全文,纳入57篇,其中有关T淋巴细胞与移植后免疫状态研究背景的文献9篇,有关调节性T细胞在移植免疫中的作用10篇,有关T淋巴细胞与移植后免疫耐受关系的文献17篇,有关T淋巴细胞与移植后免疫耐受研究前景的文献21篇。结果与结论：T淋巴细胞是调节机体免疫应答一类重要的免疫细胞。接受同种异体肝移植后,受体发生免疫排斥还是免疫耐受与免疫系统中T淋巴细胞的亚群及其功能密切相关。通过阻断或诱导T淋巴细胞的某些功能可以诱导宿主免疫耐受。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

Tissue homeostasis and cancer

Epithelial cells are known to release an important amount of cytokines capable to modulate immune system functions. On the other hand, immune system cells can release cytokines, which play an important role in the control of the growth of epithelial cells. In this paper, we stand the hypothesis that a mutual (reciprocal) growth regulation exists between epithelial cells and immune system. We propose a model describing plausible cytokine circuits that may regulate (inhibit) both epithelial growth and epithelial inflammation. In addition, we describe how dysfunction of these circuits could lead to tumoral growth, excessive inflammation or both. A failure in the regulation of epithelial growth by the immune system could give rise to a neoplasm, and a failure in the regulation of the immune system by the epithelium could give rise to inflammatory or autoimmune diseases. This model may satisfactorily explain the link between inflammation and cancer.     

Mechanisms of immune regulation in the peripheral nervous system

The peripheral nervous system (PNS) is a target for heterogenous immune attacks mediated by different components of the systemic immune compartment. T cells, B cells, and macrophages can interact with endogenous, partially immune-competent glial cells and contribute to local inflammation. Cellular and humoral immune functions of Schwann cells have been well characterized in vitro. In addition, the interaction of the humoral and cellular immune system with the cellular and extracellular components in the PNS may determine the extent of tissue inflammation and repair processes such as remyelination and neuronal outgrowth. The animal model experimental autoimmune neuritis (EAN) allows direct monitoring of these immune responses in vivo. In EAN contributions to regulate autoimmunity in the PNS are made by adhesion molecules and by cytokines that orchestrate cellular interactions. The PNS has a significant potential to eliminate T cell inflammation via apoptosis, which is almost lacking in other tissues such as muscle and skin. In vitro experiments suggest different scenarios how specific cellular and humoral elements in the PNS may sensitize autoreactive T cells for apoptosis in vivo. Interestingly several conventional and novel immunotherapeutic approaches like glucocorticosteroids and high-dose antigen therapy induce T cell apoptosis in situ in EAN. A better understanding of immune regulation and its failure in the PNS may help to develop improved, more specific immunotherapies.     

Protective autoimmunity as a T-cell response to central nervous system trauma: prospects for therapeutic vaccines.

Immune activity in general, and autoimmunity in particular, have long been considered as harmful in the context of central nervous system (CNS) trauma. Increasing evidence suggests, however, that the injured CNS can benefit from autoimmune manipulations. Active or passive immunization with CNS-associated self antigens was shown to promote recovery from a CNS insult. It is now also evident that this beneficial 'autoimmunity' is not solely an outcome of immune manipulation but is also a physiological response, evoked by a non-pathogenic insult and apparently designed to counteract the insult-related toxicity which is induced in part by essential physiological compounds present in excess of their normal levels. It appears that when the buffering capacity of constitutive local mechanisms (transporters, enzymes, etc.) that normally regulate these compounds is exceeded, assistance is recruited from the immune system. Like the overactive physiological compounds themselves, the immune system needs to be rigorously regulated in order to produce adequate phagocytic activity and the required quantity of cytokines and growth factors at the right time and place. Boosting of this autoimmune response is potentially a powerful strategy for neuroprotective therapy.     

Neuro-immune-endocrine functional system and vascular pathology.

A new interpretation of the response to injury by the nervous, immune and endocrine system is proposed, in order to integrate biochemical knowledge into the respective clinical areas. The discovery that the signaling molecules of the classical nervous, immune and endocrine systems, that is, the neurotransmitters, cytokines and hormones, respectively, are expressed and perceived by the three systems, has enabled us to establish a functional concept of these systems. The hypothetical integration of different pathological processes in a functional response made up by three phases, the immediate or nervous, intermediate or immune and late or endocrine ones, makes it possible to consider that all of them represent different forms of expression of a functional response whose meaning is always the same, that is, inflammation. If the functions that characterize each one of these three phases represent the activity of the nervous, immune and endocrine systems, the biochemical knowledge could be integrated into the functional meaning of each system.     

Immunoregulatory role of neurotransmitters

The nervous and endocrine systems modulate the immune system functions through releasing neurotransmitters, neuropeptides and endocrine hormones as they regulate the other physiological functions. The immune system in turn communicates with the nervous and endocrine systems through secreting immunocompetent substances. In this report we review our concepts and evidence concerning the immunoregulatory role of acetylcholine (ACh) and monoamine neurotransmitters which include noradrenaline (NA), 5-hydroxytryptamine (5-HT) and dopamine (DA). The immunoregulatory role comprises two aspects, the modulation of immune functions by neurotransmitters and the effect of the immune system on nervous system functions. The inhibition of ACh biosynthesis in the central nervous system (CNS) caused the enhancement of the humoral immune response of rats to sheep red blood cells (SRBC); by contrast, the inhibition of acetylcholinesterase (AChE) activity in the CNS resulted in the suppression of the immune response. It seems that ACh in the brain plays an immunoinhibitory role. The role can be blocked by atropine, a muscarinic antagonist, but not by hexamethonium, a nicotinic antagonist. During the humoral immune response (days 3–6 after SRBC injection), activity of AChE in the hypothalamus and hippocampus was strikingly lower. It is suggested that a functional connection is present in the ACh of the brain and the immune system. In vitro, ACh at 10⁻⁹ to 10⁻⁴ mol/l dose range significantly strengthened the spleen cell proliferation induced by concanavalin (Con A). The action of ACh only occurred either before or just after T lymphocytes were activated through muscarinic cholinergic receptors. In vivo, the depletion of monoamine neurotransmitters or only NA in the CNS caused the impairment of the anti-SRBC response of rats. During the phases of days 2–7 post-immunization, the metabolic alterations of NA, 5-HT and DA emerged in the CNS and the lymphoid organs of rats, which mainly exhibited that in the peak periods of the antibody response, the metabolism of the monoamine neurotransmitters in the hypothalamus and hippocampus was markedly increased, but NA content in the spleen and thymus was significantly decreased. These results provide evidence for the bidirectional information exchange network between the monoamine neurotransmitters and the immune system. Exposure to NA (at 10⁻⁸–10⁻⁵ mol/l concentration range) in vitro was shown to inhibit the Con A-induced proliferation of the rat spleen cells. This effect of NA was related to the early events involved in the initiation of T cell proliferation and was mediated by either alpha- or beta- adrenergic receptors. The evidence that altering 5-HT level in the central or peripheral nervous systems through various ways of administering the drugs to regulate 5-HT biosynthesis led to the variations of the antibody response, and that cyproheptadine, an antagonist of serotoninergic receptors, can block the action of 5-HT show that 5-HT may exert an immunoinhibitory effect, which appears to be mediated via the peripheral mechanism to relate to the 5-HT receptors. However, the antibody response can cause changes in 5-HT metabolism in the CNS. The possible reasons for these results are discussed. Collectively, the antibody response arouses the metabolic variations of ACh, NA, 5-HT and DA in the central and peripheral nervous systems and then, these alterations can in turn influence immune function through neurotransmitter relevant receptors present on the immunocytes. The purpose of this interaction is most likely to maintain the homeostasis of the immune and other physiological functions.     

TH1／TH2细胞平衡与病毒性肝炎

TH细胞是机体重要的免疫调节细胞,TH1、TH2、TH03种,分别产生不同的细胞因子调节细胞和体液免疫、TH1和TH2细胞可通过所产生的细胞因子发挥相互调节和制约作用。TH1/TH2细胞的调节对维持机体正常的免疫功能非常重要,现已知许多免疫性疾病与TH1/TH2细胞的失衡有关。本文主要阐述HBV和HCV这2种肝炎病毒感染与TH1/TH2细胞平衡的关系。     

Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression

Overwhelming inflammatory immune response can result in systemic inflammation and septic shock. To prevent excessive and deleterious action of proinflammatory cytokines after they have produced their initial beneficial effects, the immune system can release several anti-inflammatory mediators, including interleukin-10, interleukin-1 receptor antagonist, and soluble tumor necrosis factor receptors, thus initiating a compensatory anti-inflammatory response syndrome. However, in vivo the delicate balance between pro- and anti-inflammatory responses is additionally controlled by the central nervous system. Therefore, proinflammatory cytokines stimulate the hypothalamic-pituitary-adrenal axis and enhance sympathetic nerve system activity. The mediators of these neuroimmune pathways can again suppress immune cell functions to control systemic inflammation. The question is, however, what happens if the immunoinhibitory CNS pathways are activated without systemic inflammation? This can result from production of cytokines in the brain following infection, injury, or ischemia or in response to various stressors (e.g., life events, depression, anxiety) or directly from brainstem irritation. The answer is that this may generate a brain-mediated immunodepression. Many animal and clinical studies have demonstrated a stress and brain cytokine mediated decrease in the cellular immune response at the lymphocyte level. More recently, the importance of monocytes in systemic immunocapacity has been shown. Monocytic inactivation with decreased capability of antigen presentation and depressed secretion of proinflammatory cytokines increases the risk of infectious complications. Interestingly, cytokines in the brain and other stressors can also generate systemic immunodepression at the monocyte level. In this scenario the catecholamine-induced release of the potent anti-inflammatory cytokine interleukin-10 is a newly discovered mechanism of the brain-mediated monocyte deactivation in addition to the "well known" immunosuppressive action of glucocorticoids. Furthermore, other neuropeptides such as alpha-melanocyte-stimulating hormone and beta-endorphin which can be released in stressful situations have also inhibitory effects on immune cells. Thus mediators of the CNS are implicated in the regulation of immune functions and may play a role in both conditioning the host's response to endogenous or exogenous stimuli and generating a "brain-mediated" immunodepression.