肿瘤免疫中的细胞凋亡

在肿瘤免疫编辑的三个阶段：清除、平衡和逃逸,细胞凋亡发挥重要作用。清除阶段,免疫细胞通过诱导肿瘤细胞凋亡发挥免疫清除作用;平衡阶段,在免疫选择作用下,肿瘤细胞凋亡促进肿瘤恶性演进;逃逸阶段,肿瘤细胞凋亡耐受性增强,进而反向促使免疫细胞凋亡,削弱肌体免疫力,产生免疫耐受。     

睾丸Sertoli细胞构建人工免疫赦免区的研究启示

异源胰岛细胞移植中免疫排斥的问题一直是制约胰岛移植成功运用于临床的主要障碍。最近有研究表明,睾丸Sertoli细胞能够表达有效诱导免疫排斥细胞凋亡的Fas配体。因此,通过人工方式为异休移植细胞构建一个类似的局部免疫赦免微环境将成为可能。     

机体免疫反应与肿瘤发生的理性思考

在肿瘤发生的各个阶段中,机体免疫系统的免疫监控功能始终贯穿于每一个阶段.机体免疫系统和致癌因素是矛盾消长的辩证关系,虽然机体具有严密的免疫监视机制,但某些情况下恶变细胞也可能通过多种机制逃避机体的免疫监视,使机体的免疫系统出现障碍而无法对肿瘤细胞进行识别和杀伤,从而导致肿瘤的发生.     

针对T细胞介导的胰岛自身免疫的治疗策略

1A型糖尿病是由T细胞所介导的器官特异性自身免疫性疾病。人们利用转基因技术、自身抗原疫苗接种、单克隆抗体治疗等新兴技术通过诱导自身免疫耐受,改变免疫调节因子,调节细胞凋亡等途径阻止了自身免疫反应对胰岛的攻击。这些针对其发病机制所提出的新型治疗策略让人们看到了治疗自身免疫型糖尿病的希望。     

从自然选择学说看肿瘤免疫

当今人类生存的环境发生了变化,肿瘤的发病率和病死率也越来越高,肿瘤细胞面对强大的免疫系统生存下来,说明肿瘤生存能力增强已经适应了其生存环境,这是环境对肿瘤细胞自然选择的结果。自然选择学说始终贯穿于肿瘤免疫学的免疫监视理论和免疫编辑学说之中,从自然选择的角度看肿瘤免疫学,将为肿瘤治疗策略开创一条新路。     

严重脓毒症与免疫功能障碍

脓毒症多呈现典型的促炎效应和抗炎反应,并与获得性免疫功能障碍同时出现,且免疫细胞中超过80％的基因表达发生改变。由于单核／巨噬细胞细胞因子谱的改变、主要组织相容性复合体Ⅱ类抗原（MHCⅡ）及共刺激分子表达下降以及树突状细胞的凋亡,诱发细胞免疫功能下降;中性粒细胞活性降低和补体系统的激活,又增加感染易感性。T淋巴细胞表现...     

The central nucleus of the amygdala; a conduit for modulation of HPA axis responses to an immune challenge?

Physical stressors such as infection, inflammation and tissue injury elicit activation of the hypothalamic-pituitary-adrenal (HPA) axis. This response has significant implications for both immune and central nervous system function. Investigations in rats into the neural substrates responsible for HPA axis activation to an immune challenge have predominantly utilized an experimental paradigm involving the acute administration of the pro-inflammatory cytokine interleukin- 1β (IL-1β). It is well recognized that medial parvocellular corticotrophin-releasing factor cells of the paraventricular nucleus (mPVN CRF) are critical in generating HPA axis responses to an immune challenge but little is known about how peripheral immune signals can activate and/or modulate the mPVN CRF cells. Studies that have examined the afferent control of the mPVN CRF cell response to systemic IL-1β have centred largely on the inputs from brainstem catecholamine cells. However, other regulatory neuronal populations also merit attention and one such region is a component of the limbic system, the central nucleus of the amygdala (CeA). A large number of CeA cells are recruited following systemic IL-lβ administration and there is a significant body of work indicating that the CeA can influence HPA axis function. However, the contribution of the CeA to HPA axis responses to an immune challenge is only just beginning to be addressed. This review examines three aspects of HPA axis control by systemic IL-1β: (i) whether the CeA has a role in generating HPA axis responses to systemic IL-1β, (ii) the identity of the neural connections between the CeA and mPVN CRF cells that might be important to HPA axis responses and(iii) the mechanisms by which systemic IL-Iβ triggers the recruitment of CeA cells.     

Variables influencing outflow-inflow interpretations tracking performance: predictability of target motion, transfer function, and practice

Experimental evidence can be found in support of either outflow or inflow theories of voluntary action. Accordingly, the empirical problem becomes one of ascertaining fundamental conditions under which the dichotomy plainly manifests itself. Using a within-subjects design, six undergraduates were given pursuit tracking training. The independent variables were (a) presence or absence of regularity (predictability) in the back-and-forth motion of the target, (b) type of control stick (with attendant proprioceptive feedback) used to drive the cursor, and (c) practice. The dependent variable was the time integral of error. The following results were significant (p less than .05, two-tailed): (a) A pressure stick is better than a freely moving one when tracking a random target; this finding supports a reactive force inflow model. The converse is true for a predictable target and is therefore supportive of an outflow interpretation. (b) Regardless of kind of target motion, an unloaded stick is better than an elastically loaded one at the beginning of training (outflow support) but worse by the end of training (inflow support). It is concluded that the motor outflow versus motor inflow dispute is amenable to parametric resolution.     

从卡介苗成功治疗膀胱癌论肿瘤的免疫治疗

卡介苗(BCG)膀胱内灌注是治疗浅表性膀胱癌一种最有效的方法。通过对治疗后的监测发现,卡介苗灌注后可引发肿瘤部位显著的固有免疫和适应性免疫细胞反应,体内大多数的抗肿瘤免疫效应细胞参与这一反应过程。这一结果表明,有效的肿瘤免疫治疗必须由固有免疫和适应性免疫细胞协同作用才能完成。     

从抗原提呈细胞到抗原提呈小体

树突状细胞是体内专职抗原提呈细胞,在抗肿瘤免疫治疗中发挥重要作用。而exosome是树突状细胞分泌的一种膜性微囊小体,富含树突状细胞的MHC-I/II类分子、协同刺激分子等多种生物活性分子,亦在抗肿瘤免疫应答中发挥重要作用。从树突状细胞到exosome,是细胞性瘤苗向非细胞性瘤苗的飞跃,对免疫治疗研究产生极为深远的影响。     

Neuroimmune stress responses: reciprocal connections between the hypothalamus and the brainstem

Hypothalamic nuclei, particularly the paraventricular nuclei (PVN), are important brain sites responsible for eliciting stress responses following a systemic immune challenge. The activation of PVN cells by a systemic immune challenge is critically dependent on the integrity of inputs from brainstem cells situated in the nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM). Interestingly, a descending pathway from the PVN to the brainstem, recruited by systemic immune challenge, might also exist. It is well documented that PVN neurons innervate the NTS and VLM and recent evidence from our laboratory shows that lesions of the PVN reduce brainstem cell responses elicited by a systemic bolus of the proinflammatory cytokine interleukin-1beta (IL-1beta). Although a number of different PVN divisions are candidates for the source of inputs to the brainstem, we have demonstrated that the majority of descending PVN projections recruited by systemic IL-1beta arise from cell bodies localized in the medial and lateral parvocellular PVN. These findings suggest that central nervous system responses to an immune challenge are likely to involve complex reciprocal connections between the PVN and the brainstem, whereby brainstem cell populations could essentially act as integratory sites for descending and ascending immune signals. For instance, these brainstem pathways may have significant implications not only for the regulation of central hypothalamic and extra-hypothalamic targets but also the autonomic nervous system.     

抑郁症的心理神经免疫学研究：细胞因子的作用

免疫系统在一些心理精神障碍中具有重要作用,抑郁症可看作是一种心理神经免疫紊乱性疾病。生理应激和心理应激能激活免疫系统,导致细胞因子的产生,从而影响中枢神经系统的多个方面,包括神经递质代谢、神经内分泌功能、神经可塑性以及与行为改变有关的信息过程。细胞因子不仅由免疫活性细胞分泌,也能被神经胶质细胞和神经细胞合成和分泌,它在抑郁症中的作用可能会在揭示抑郁障碍机制上有新突破,并可能作为今后药物治疗的靶点进入临床领域     

Cultivating a healthy neuro‐immune network: A health psychology approach

The field of psychoneuroimmunology (PNI) examines interactions among psychological and behavioral states, the brain, and the immune system. Research in PNI has elegantly documented effects of stress at multiple levels of the neuro‐immune network, with profound implications for both physical and mental health. In this review, we consider how the neuro‐immune network might be influenced by “positive” psychological and behavioral states, focusing on positive affect, eudaimonic well‐being, physical activity, and sleep. There is compelling evidence that these positive states and behaviors are associated with changes in immune activity in the body, including reductions in peripheral inflammatory processes relevant for physical health. Growing evidence from animal models also suggests effects of positive states on immune cells in the brain and the blood‐brain barrier, which then impact critical aspects of mood, cognition, and behavior. Tremendous advances are being made in our understanding of neuro‐immune dynamics; one of the central goals of this review is to highlight recent preclinical research in this area and consider how we can leverage these findings to investigate and cultivate a healthy neuro‐immune network in humans.     

胞外体认识之新进展

胞外体是由多种细胞分泌的一种膜性小囊泡,参与多种生理及病理生理过程。近年研究发现,由抗原提呈细胞分泌的胞外体富集MHCI/II类分子、协同刺激分子、热休克蛋白70~90等多种生物活性分子于一身,在体内外免疫调节中起关键作用。就胞外体的基本特征及其作为一种新型的亚细胞疫苗在抗肿瘤和抗病毒免疫中的应用前景予以综述。     

Anomalous brain dominance and the immune system: Do left-handers have specific immunological patterns?

Geschwind and Behan (1982) and Geschwind and Galaburda (1985a, 1985b, 1985c) suggested a correlation between brain laterality and immune disorders. To test whether this hypothesis holds true not only for the frequency of immune diseases and circulating autoantibodies, but extends also to cellular immunity, we examined the association between handedness and markers of cellular immunity. Twenty-seven left-handed and 37 right-handed subjects were serologically screened for cellular parameters and 22 left-handed subjects were typed for human leukocyte antigen (HLA). When compared to the right-handers, the left-handed group showed a significant decrease in the inflammatory cell types CD3(+) T cells (total T cells), CD4(+) T cells (T-helper cells), and HLA-Dr (MHC-II, antigen-presenting cells) as well as in the CD19(+) cells (B cells) and CD16/CD57(+) cells (natural killer cells). We assume a relationship exists between cerebral hemispheric specialisation and the immune system not only for humoral but also for cellular immunity, and we discuss the role of the major histocompatibility complex in neurological and immunological development.     

The use of digital rheoplethysmography for the study of psychogenic and neurogenic factors in man

The use of the RPG in the qualitative and quantitative study of the state of the intact digital vasculature of intact man is illustrated and emphasized. Rheoplethysmography is the only method for quantitatively recording continuously and simultaneously the volumes and rates of inflow, outflow and the differences between inflow and outflow and the rate of basal blood flow in the digits of intact man or in any organ or tissue that can be isolated in a plethysmographic cup. The effects of psychogenic and neurogenic factors on the peripheral circulation of man were studied with the RPG, and the results demonstrate how useful this method is for such studies of the fingertip.     

Proprioceptive feedback as a mediator in interlimb timing

Prior findings regarded as evidence for proprioceptive feedback as a mediator in interlimb timing can also be interpreted as evidence for motor outflow because they came from research that had subjects make voluntary movements, and such movements allow for both feedback and outflow to operate. The present study was designed to resolve this controversy by determining if these findings could be replicated with passive movements which allow for feedback, but not outflow, to operate. The interlimb timing task studied was one where subjects made the timing response with their right hand while moving their left arm during the 1.5-sec interval to be timed. Three groups of 16 male college students performed 50 trials of the right-hand response with knowledge of results, under one of three left-arm conditions: (a) passive movement, (b) voluntary movement, and (c) no movement. The results indicated that the findings were replicated with passive movements and this was interpreted as support for the involvement of proprioceptive feedback in interlimb timing.     

骨髓干细胞移植治疗1型糖尿病的理论与实践

胰岛移植作为治疗1型糖尿病较理想的方法,由于其供体不足而受到限制。干细胞具有极强的自我更新能力与多向分化潜能,可成为提供1型糖尿病胰岛β细胞良好的细胞来源。造血千细胞移植通过诱导免疫耐受,修复受损胰腺组织改善胰岛功能。间充质干细胞移植可分化为胰岛β细胞,且通过免疫调节改善胰岛细胞微环境。     

An electrophysiological model of human visual reaction time

Human visual reaction times were fractionated into component latencies measuring visual reception time, opto-motor integration time, central motor outflow time, and peripheral motor time on the basis of evoked cortical activity recorded from the intact scalp and the occurrence of the response electromyogram. Normative data are presented for a right-foot dorsiflexion task studied on 18 male subjects, together with an analysis of inter- and intra-subject variability in response timing. Faster reactors were found to display briefer opto-motor integration times and motor times, while an individual's faster responses were characterized by shorter motor outflow times and motor time. These results are interpreted in terms of varying physiological mechanisms.     

通过打破抗原特异性T细胞免疫耐受控制慢性HBV感染

乙型肝炎病毒(HBV)感染诱导机体抗病毒免疫应答,若不能对病毒有效清除,体内抗原特异的CTL降低,出现抗原特异性T细胞免疫耐受,造成慢性肝脏炎症。分析HBV感染时抗原特异性T细胞免疫耐受机制,并通过打破免疫耐受预防HBV感染。