免疫系统在青光眼发病机制中的作用

青光眼曾被认为是一种病因单纯疾病,近些年研究表明,是由多原因导致的视神经永久性损伤和视野丢失的一类疾病。而免疫系统在青光眼的视网膜视神经损害中所起的作用应该是双重的。一方面自身免疫机制引起视神经损伤可以由自身抗体直接导致,也可以间接模拟对敏感抗原的自身免疫反应所引起,另一方面,免疫系统监督和调节可以对应激作出反应,从而起到一定保护作用。了解免疫系统在青光眼发病机制中的作用对于预防及治疗青光眼有着重要的意义。     

MicroRNA在免疫系统中的作用

MicroRNAs(miRNAs)是一类新型保守的非编码单链小分子RNA,广泛存在各种生物体中.miRNAs转录后水平调节基因的表达,主要通过结合到特定靶日标mRNA的3′UTRS端,导致蛋白翻译抑制或促进靶mRNA降解.miR-NAs在固有免疫和适应性免疫细胞中通过特定的表达谱调节细胞的分化和功能,其表达和功能失调将导致各种免疫性疾病发生,如癌症和自身免疫性疾病.本文中主要阐述目前miRNAs在免疫系统中的研究及其对各种自身免疫性疾病的影响.     

microRNA-155在免疫系统中的作用

microRNA( miRNAs,miRs)是一组近几年发现的、不编码蛋白质的单链小分子RNA.其在疾病发生发展过程中的作用是目前研究的热点.miRNA在免疫系统中的作用已经被广泛的研究,其不仅参与免疫系统的发生发展,而且在介导免疫系统抵抗微生物入侵机体方面起重要的作用.miR-155是免疫系统最主要的miRNA之一,其在活化的各种免疫细胞中表达普遍升高,是参与天然免疫应答和特异性免疫应答的最重要的miRNA.现就miR-155在免疫系统中的作用做一综述.     

核转录因子FOXO在免疫系统中的作用

FOXO亚家族作为一种核转录因子,在细胞的增殖、分化、代谢、凋亡及基因表达方面发挥广泛而重要的作用。它还能在T淋巴细胞、B淋巴细胞、干／祖细胞和其它免疫相关细胞中,通过调节不同的靶基因的表达而影响其功能的发挥。因此,对于FOXO功能的认识有助于阐明许多免疫相关疾病的病理生理过程,并为其治疗提供新的靶点。     

bcl-2基因在免疫系统中的作用

bc1-2是在滤泡型淋巴瘤中最先发现的与t(14;18)染色体易位相关的一种癌基因。最近研究表明,bc1-2对细胞凋亡具有调控作用,并与T细胞发育、B细胞分化以及淋巴瘤的发生、发展等方面有关。     

miRNA在免疫系统中的研究进展

微小RNA(microRNA,miRNA)是一类内源性的长度约22个核苷酸的非编码小分子RNA,能够在转录后水平调节mRNA表达.miRNA在线虫、果蝇、植物、哺乳动物,甚至病毒中广泛存在.miRNA基因以单拷贝、多拷贝或基因簇等多种形式存在于基因组中,而且绝大部分定位于基因间隔区,其转录独立于其他基因.     

人内皮抑素在大肠杆菌中的高效表达及活性研究

目的:表达人内皮抑素蛋白,制备多克隆抗体,检测其生物学活性。方法:采用PCR法扩增人内皮抑素基因,构建pGEX-ES融合表达载体,IPTG(异丙基硫代-β-D半乳糖苷)诱导表达。初步纯化的内皮抑素包含体蛋白制备兔多克隆抗体,Western-blot检测其在小鼠肝、肾等的表达。亲和纯化的内皮抑素蛋白用内皮细胞抑制实验检测其生物学活性。结果:诱导表达的人内皮抑素蛋白经凝血酶酶切后,分子量约为 20kD,具有抑制内皮细胞生长的活性。制备的多克隆抗体检测出内皮抑素在小鼠肝、肾等组织的表达。结论:人内皮抑素的成功表达及抗体制备为抗血管生成治疗实体瘤的研究及检测奠定实验基础.     

树突状细胞在肠道黏膜免疫系统中的作用

在针对大量的外环境无害抗原、食物蛋白和共生菌群所引发的免疫耐受与针对入侵病原体引发的免疫反应之间维持一种平衡的状态是肠道黏膜免疫系统内的中心事件。这种状态，一方面保证了肠道黏膜免疫系统自身的稳定，另一方面也保证了机体内环境的稳定。那么，肠道黏膜免疫系统怎样区分这些无害信号和有害信号呢？研究发现，树突状细胞（dendritic cell，DC）在其中发挥了“决策者”的作用。     

miRNA在免疫系统中的研究进展

microRNA(miRNA)是一类长度约21~25碱基的非编码蛋白质的单链小分子RNA,广泛存在于多细胞生物和病毒体内,主要通过核酸序列互补匹配结合到特定的靶mRNA上,抑制靶mRNA翻译过程或降解靶mRNA,是一种起负调控作用的分子。目前越来越多的研究显示,miRNA广泛参与了生物体多种生理过程,且相关研究报道也表明其表达及功能失调可能导致肿瘤发生、白血病以及病毒感染等多种病理现象。本文主要阐述目前在免疫系统中对miRNA研究的一些进展情况。     

Expression of cortistatin and MrgX2, a specific cortistatin receptor, in human neuroendocrine tissues and related tumours

Cortistatin (CST), a novel hormone originally described in the rat, mouse, and human cerebral cortex, displays structural and functional similarities to somatostatin (SRIF). CST binds to all five somatostatin receptors and, differently from SRIF, also binds to MrgX2, which has recently been identified as its specific receptor. Little is known about the distribution of CST and MrgX2 in peripheral non-tumour and neoplastic tissues. The aim of the present study was therefore to determine by immunohistochemistry and mRNA analysis (RT-PCR) the distribution of CST and MrgX2 in 56 human non-tumour and 108 tumour tissues, with special reference to neuroendocrine tissue types. Despite the high level of CST mRNA expression in non-tumour and tumour (both neuroendocrine and non-neuroendocrine) tissues, the presence of immunoreactive CST was confirmed in a subset of gastroenteropancreatic, parathyroid, and pituitary non-tumour cells only, and showed a predominantly focal pattern in most neuroendocrine tumours. Co-localization experiments in the gastroenteropancreatic system demonstrated that the normal CST-producing cells are delta cells, while in the adenohypophysis no preferential co-localization of CST with any of the pituitary hormones was observed. MrgX2 mRNA was variably detected in the hypothalamus, pituitary, thyroid, lung, gastroenteropancreatic tract, testis, and ovary, and was negative in the cerebral cortex, parathyroid, and adrenal, as well as in a variety of tumour types. Conversely, immunolocalization of MrgX2 protein was restricted to neurohypophysis and testis, whilst all tumours analysed were negative. A possible explanation for the discrepancy between RT-PCR and immunohistochemistry is that MrgX2 protein was widely detected in blood vessels, scattered lymphocytes, and gastrointestinal ganglia in both normal and neoplastic samples. The findings demonstrate a selective distribution of CST in normal and neoplastic neuroendocrine tissues, suggesting that CST might have a broader functional role than previously assumed, whereas possible autocrine/paracrine actions via its recently described specific receptor MrgX2 are restricted to selected tissues.     

Control of ovarian function by the immune system: Is this a plausible and necessary hypothesis?

A recently presented hypothesis, according to which cyclic selection of a specific number of follicles for ovulation is brought about by immune mechanisms, will be discussed critically. The arguments and conclusions within the framework of this hypothesis are either not convincing or even at variance with well established facts. It is questioned whether there is any need for such a dramatic extension of the commonly accepted concept for neuroendocrine control of ovarian function.     

Oscillations in the immune system

Summary:  Oscillations are surprisingly common in the immune system, both in its healthy state and in disease. The most famous example is that of periodic fevers caused by the malaria parasite. A number of hereditary disorders, which also cause periodic fevers, have also been known for a long time. Various reports of oscillations in cytokine concentrations following antigen challenge have been published over at least the past three decades. Oscillations can also occur at the intracellular level. Calcium oscillations following T-cell activation are familiar to all immunologists, and metabolic and reactive oxygen species oscillations in neutrophils have been well documented. More recently, oscillations in nuclear factor κB activity following stimulation by tumor necrosis factor α have received considerable publicity. However, despite all of these examples, oscillations in the immune system still tend to be considered mainly as pathological aberrations, and their causes and significance remained largely unknown. This is partly because of a lack of awareness within the immunological community of the appropriate theoretical frameworks for describing and analyzing such behavior. We provide an introduction to these frameworks and give a survey of the currently known oscillations that occur within the immune system.     

The state of the immune system in thyroidectomized rats

Disorders in the immune system manifesting in decreased weight and cellularity of lymphoid organs, decreased count of large granular lymphocytes, suppression of the immune response and metabolic activity of macrophages were observed in experimental animals 1-6 months after thyroidectomy. The intensity of these disorders depends on the period elapsed after the surgery. These disorders can result from not only changes in the levels of the pituitary-thyroid hormones, but also disturbances in the endocrine function of the thymus in thyroidectomized animals.     

Ovarian function and the immune system.

A hypothesis is presented on the interaction between the immune system and ovary in the regulation of the reproductive system and in the origin of some of its disorders. It has been suggested that the beginning, duration and age dependent failure of ovarian ovulatory function depends among other things on the adequate relationship between the immune system and approriate ovarian target structures. The cyclicity of ovarian function is considered to be primarily dependent on the induction of a specific cyclic immune response to the ovary. Similarly, the selection of a species-specific number of ovulating follicles during sexual maturity is thought to be ensured by immune mechanisms. This hypothesis, on the role of the immune system in regulation of ovulatory ovarian function respects the physiological effect of gonadotropins and steroids on the ovarian structures. The interaction between the ovary and the hypothalamus-pituitary system appears to be modulated by the relationship between the ovary and the immune system.     

Mast cell functions in the innate skin immune system

Mast cells are not only potent effector cells in allergy, but are also important players in protective immune responses against pathogens. Most of our knowledge about mast cells in innate immunity is derived from models of sepsis, whereas their role in innate immune responses of the skin has largely been neglected in the past. Their particular pattern of distribution in the skin and their ability to sense and react to pathogens and other danger signals indicate that mast cells can be important sentinels and effector cells in skin immune responses. The recent findings reviewed here have confirmed this hypothesis and have established a prominent role for skin mast cells in innate immunity.     

Non-zero-sum microbiome immune system interactions

Fundamental asymmetries between the host and its microbiome in enzymatic activities and nutrient storage capabilities have promoted mutualistic adaptations on both sides. As a result, the enteric immune system has evolved so as not to cause a zero-sum sterilization of non-self, but rather achieve a non-zero-sum self-reinforcing cooperation with its evolutionary partner the microbiome. In this review, we attempt to integrate the accumulated knowledge of immune—microbiome interactions into an evolutionary framework and trace the pattern of positive immune—microbiome feedback loops across epithelial, enteric nervous system, innate, and adaptive immune circuits. Indeed, the immune system requires commensal signals for its development and function, and reciprocally protects the microbiome from nutrient shortage and pathogen outgrowth. In turn, a healthy microbiome is the result of immune system curatorship as well as microbial ecology. The paradigms of host–microbiome asymmetry and the cooperative nature of their interactions identified in the gut are applicable across all tissues influenced by microbial activities. Incorporation of immune system influences into models of microbiome ecology will be a step forward toward defining what constitutes a healthy human microbiome and guide discoveries of novel host–microbiome mutualistic adaptations that may be harnessed for the promotion of human health.     

Following TRAIL's path in the immune system

The members of the tumour necrosis factor (TNF) superfamily of cytokines play important roles in the regulation of various immune-cell functions. Likewise, induction of cell death by apoptosis is indispensable for the normal functioning of the immune system. There are two major pathways of apoptosis induction. The intrinsic, or mitochondrial, pathway is regulated by the activation and interaction of members of the Bcl-2 family. The extrinsic, or death receptor, pathway is triggered by certain TNF family members when they engage their respective cognate receptors on the surface of the target cell. Hence, cell-to-cell-mediated death signals are induced by activation of these death receptor–ligand systems. Besides TNF itself and the CD95 (Fas/APO-1) ligand (FasL/Apo1L), the TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) belongs to the subfamily of ligands that is responsible for extrinsic induction of cell death. Depending on their status of stimulation, TRAIL can be expressed by various cells of the immune system, amongst them natural killer (NK) cells, T cells, natural killer T cells (NKT cells), dendritic cells and macrophages. TRAIL has been implicated in immunosuppressive, immunoregulatory and immune-effector functions. With respect to pathological challenges, TRAIL and its receptors have been shown to play important roles in the immune response to viral infections and in immune surveillance of tumours and metastases. In this review we summarize the current knowledge on the role of TRAIL and its receptors in the immune system and, based on this, we discuss future directions of research into the diverse functions of this fascinating receptor–ligand system.