白细胞免疫球蛋白样受体家族及其与免疫相关疾病的关系

当病原体感染时,机体天然免疫系统依赖于不同受体分子介导的免疫反应。天然免疫细胞的免疫反应程度可能是通过细胞多种激活和抑制性受体分子介导的信号通路来整合调控的。免疫球蛋白超家族在免疫反应中作为抗原受体、共刺激蛋白、黏附分子、免疫调节分子发挥重要作用。其中一组被称作白细胞免疫球蛋白样受体[leukocyteimmunoglobulin（Ig）-likereceptors,LILRs]或免疫球蛋白样转录物（ILTs）的分子家族既参与先天性免疫,     

生物信息学预测与肝细胞肝癌患者预后相关的免疫相关基因

目的 通过生物信息学分析预测肝细胞肝癌(HCC)患者预后免疫相关基因并建立预后预测模型。方法 通过差异分析鉴定HCC组织中的免疫相关基因,使用单因素、多因素比例风险回归模型(Cox)、套索算法(LASSO)建立风险预后预测模型。使用C指数、受试者工作特征(ROC)曲线、校准曲线和决策曲线评价预后模型的预测效能。此外,将风险评分用于患者分层进而评估不同风险水平患者的预后差异。结果 通过生物信息学分析,发现HCC患者至少存在1403个免疫相关基因,主要集中在免疫反应、适应性免疫反应、免疫球蛋白产生等生物过程以及细胞因子相互作用、趋化因子信号通路和同种异体移植排斥等通路。单因素Cox分析发现,53个免疫相关基因与预后相关,进一步通过LASSO和多因素Cox回归分析筛选出8个预后免疫相关基因,包括长链非编码RNA AC125238.1、细胞色素P450氧化酶1A2(CYP1A2)、纤胶凝蛋白3(FCN3)、肝癌衍生生长因子样蛋白1(HDGFL1)、脂质运载蛋白2(LCN2)、线粒体编码的细胞色素C氧化酶Ⅱ假基因12(MTCO2P12)、肽基精氨酸脱亚氨酶3(PADI3)和G蛋白信号调节因子16...     

线粒体DNA相关疾病的分子遗传学研究

在儿童退行性疾病中 ,诸如发育延迟、感觉运动障碍、惊厥、糖尿病以及器官衰竭等 ,线粒体功能紊乱是一个相当常见的病因[1] 。近年来线粒体ＤＮＡ(ｍｔＤＮＡ)突变及其致病作用也是一些晚发性疾病如Ａｌｚｈｅｉｍｅｒ’ｓ病、肿瘤及Ｐａｒｋｉｎｓｏｎ’ｓ病的研究热点。据Ｆｉｎｌａｎｄ的一项研究表明ｍｔＤＮＡ相关疾病的发病率≥ 16 3 10万。自从 1963年发现ｍｔＤＮＡ和 1988年首次报道致病性ｍｔＤＮＡ突变以来 ,迄今已发现至少 97个点突变和很多的ｍｔＤＮＡ重排 (缺失、重复 ) ,ｍｔＤＮＡ突变业已成为线粒体疾病的重要病因之一[1,…     

病原体相关分子模式——一种倍受关注的天然免疫活化剂

病原体相关分子模式(pathogen-associated molecular pattems，PAMPs)是存在于低等微生物或其细胞壁上的一些保守成分，由于这些成分不存在于高等哺乳动物中，藉此哺乳动物参与天然免疫的细胞可以区分出“自己”与“非己”成分。TOU样受体是PAMPs的结合受体，不同的PAMPs可以被不同的TOU样受体所识别或组合识别，然后通过一系列蛋白质级联反应激活转录因子NF-κB和Jun/Fos，从而有效地活化天然免疫系统。PAMPs作为一种天然的免疫佐剂在感染性疾病和肿瘤的防治中具有潜在的巨大的应用价值。     

肝脏的免疫功能

肝脏不仅具有内分泌功能,而且可参与机体局部或整体水平的免疫调节,尤其发现了肝脏是胸腺以外的Ｔ细胞分化的重要场所。     

真菌细胞壁病原相关分子模式TLR/Dectin-1通路及相关细胞因子的免疫作用

侵袭性真菌感染(IFI)是致ICU患者死亡的重要原因之一。机体通过天然免疫重要的模式识别受体(PRR)Toll样受体(TLR)及C型凝集素受体(CLR)与病原相关分子模式(PAMP)识别后启动抗真菌免疫反应。目前明确磷脂甘露聚糖(PLM)的识别主要依赖TLR2和TLR4;β-葡聚糖经TLR2/树突状细胞相关性C型凝集素-1(Dectin-1)或只经Dectin-1识别。PLM和β-葡聚糖被识别后及经Dectin-1驱动获得性免疫后产生一系列下游细胞因子,一些下游细胞因子的免疫作用对不同组织有所不同、不确定或存在争议,一些免疫反应在细节上还没有详尽描述。因此,深入研究PAMP与PRR相互作用及其细胞因子对免疫调节影响,对IFI的预防治疗有重要意义。     

免疫老化与肝脏受损易感性

免疫老化与肝脏受损易感性孙文兵１韩本立１许多因素与老化宿主肝脏受损易感性有关。本文就免疫老化（Ｉｍｍｕｎｏｓｅｎｅｓｃｅｎｃｅ）与其之间的关系作一综述。１枯否细胞与肝细胞损伤枯否细胞（ＫｕｐｆｅｒＣｅｌＫＣ）对肝细胞的调节是肝细胞维持正常生理过程的重...     

病原体相关分子模式——一种倍受关注的天然免疫活化剂

病原体相关分子模式 (pathogen associatedmolecularpatterns ,PAMPs)是存在于低等微生物或其细胞壁上的一些保守成分 ,由于这些成分不存在于高等哺乳动物中 ,藉此哺乳动物参与天然免疫的细胞可以区分出“自己”与“非己”成分。Toll样受体是PAMPs的结合受体 ,不同的PAMPs可以被不同的Toll样受体所识别或组合识别 ,然后通过一系列蛋白质级联反应激活转录因子NF κB和Jun Fos ,从而有效地活化天然免疫系统。PAMPs作为一种天然的免疫佐剂在感染性疾病和肿瘤的防治中具有潜在的巨大的应用价值。     

基于细胞焦亡与免疫相关基因构建及验证肝细胞癌预后风险模型

目的：利用生物信息学方法构建并验证细胞焦亡与免疫相关基因的肝细胞癌预后风险模型,根据其风险评分探索免疫相关性特征,以指导个性化免疫治疗。方法：从TCGA、GEO官网分别下载TCGA-LIHC和GSE14520基因表达谱,从INNATEDB和IMMPORT官网下载免疫相关基因。以TCGA为训练组,GEO为测试组,对训练组细胞焦亡基因表达谱采用Cox回归分析,筛选预后相关基因进行共识聚类分组,提取分组间差异基因与免疫相关基因的交集基因,对交集基因应用单因素Cox和Lasso回归分析,得到预后相关风险评分模型。根据训练组风险中位值划分高低风险组,利用测试组验证模型可行性,最后探索训练组富集分析（GO、KEGG、GSEA）、免疫相关性分析及模型基因蛋白表达情况。结果：共筛选出9个可靠的风险模型基因（ICAM1、S100P、FABP3、CCL20、HRG、IGHM、SPP1、C4BPA、C6）。GO富集分析显示风险差异基因主要参与各种代谢过程。KEGG富集分析显示风险差异基因主要参与补体和凝血级联信号通路。GSEA富集分析显示高风险组与致癌途径的激活密切相关。在免疫浸润、免疫相关通路及免疫检查点...     

Expression of adhesion molecules on lymphocytes/monocytes and hepatocytes in human liver grafts

The regulation of expression of adhesion molecules in human liver grafts in the course of rejection and inflammatory reactions was studied. The tissue distribution of adhesion receptor molecules and ligand molecules in graft biopsies taken during complications was compared to that in normal liver and reference biopsies taken at the time of transplantation.     

Expression of adhesion molecules in allergic lung diseases

Endothelial adherence and migration of leukocytes into tissue is mediated by different sets of adhesion molecules. The expression of these sets might not only preselect the types of leukocytes that enter the inflammatory sites, but also activate these leukocytes, induce adherence to epithelial cells, and cause the release of cytokines. Atopic asthma, extrinsic allergic alveolitis, and sarcoidosis as examples of immunologic lung diseases were investigated for the expression of adhesion molecules. Bronchial biopsies in chronic obstructive lung disease (COPD) and resected lung tissue of juvenile emphysema were chosen for controls. Immunohistochemistry was done on sections from bronchial and transbronchial biopsies and on smears from bronchoalveolar lavage cells. In all three types of immune disorders, lymphocytes expressed the integrins alpha4/beta1 (VLA4) and ICAM3, whereas lymphocytes in COPD bronchitis and in emphysema controls were unreactive. Eosinophils in atopic asthma bronchitis in contrast to COPD bronchitis also expressed both VLA4 and ICAM3. The expression of VCAM1 on endothelial cells was only seen in atopic asthma and was related to disease activity. The expression of other adhesion molecules was nonspecific. Expression of VCAM1 on endothelial cells and its ligand VLA4 on lymphocytes and eosinophils seems to be a specific event in atopic asthma. Expression of VLA4 and ICAM3 on lymphocytes, however, might be a specific event in all three immune reactions.     

Pathophysiological roles of interleukin-18 in inflammatory liver diseases

Summary: Innate immune response to microbes sometimes determines the nature of the following specific immune response. Kupffer cells, a potent constituent of innate immunity, play a key role in developing the type 1 immune response by interleukin (IL)-12 production. Furthermore, Kupffer cells have the potential to induce liver injury by production of IL-18. Propionibacterium acnes -primed lipopolysaccharide (LPS)-challenged liver injury is the prototype of IL-18-induced tissue injury, in which IL-18 acts on natural killer cells to increase Fas ligand (FasL) that causes liver injury by induction of Fas-dependent hepatocyte apoptosis. LPS induces IL-18 secretion from Kupffer cells in a caspase-1-dependent manner. Indeed, caspase-1-deficient mice are resistant to P. acnes and LPS-induced liver injury. However, administration of soluble FasL induces acute liver injury in P. acnes -primed caspase-1-deficient mice but does not do so in IL-18-deficient mice, indicating that IL-18 release in a caspase-1-independent fashion is essential for this liver injury. Therefore, a positive feedback loop between FasL and IL-18 plays an important role in the pathogenesis of endotoxin-induced liver injury.     

The roles of innate immune cells in liver injury and regeneration

For predominant abundance with liver-specific Kupffer cells, natural killer （NK） cells, and natural killer T （NKT） cdls and their rapid responses to several stimuli, the liver is considered as an organ with innate immune features. In contrast to their roles in the defense of many infectious agents like hepatitis viruses and parasites, hepatic innate immune cells are also involved in the immunopathogenesis of human clinical liver diseases and several murine hepatitis models such as concanavalin A （Con A）, lipopolysaccharide （LPS）, or polyinosinic-polycytidylic acid （Poly I：C）-induced liver injury. In this review, the destructive roles of NK cells, NKT cells and Kupffer cells in the processes of immune-mediated liver injury and regeneration will be discussed, and some putative mechanisms involving the impairment of liver regeneration caused by activated hepatic innate immune cells are also proposed.     

Estrogen receptors and their roles in the immune and respiratory systems

Estrogen is an important hormone for health in both genders. It is indispensable to glucose homeostasis, immune robustness, bone health, cardiovascular health, and neural functions. The main way that estrogen acts in the cells is through estrogen receptors (ERs). The presence of specific estrogen receptors is required for estrogen to have its characteristic ubiquitous action in almost all tissues. Estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) are the major isoforms of estrogen that are highly specific in humans and enable selective hormonal actions in different tissues. This article reviews some of the observed estrogen actions and effects in different tissues and cells through these specific receptors. This ubiquitous, almost ordinary hormone may reveal itself as a significant factor that helped us to better understand the complexity of the human immune system response against respiratory infections, including the COVID-19, and especially in the current state of this painful pandemic.     

Regulatory T cells and their roles in immune dysregulation and allergy

The main function of the immune system is to fight off potential infections, but also to maintain its activity below a level that would trigger self-reactivity. Regulatory T cells (Tregs) such as forkhead box P3⁺ (FOXP3) Tregs and type 1 regulatory T cells (Tr1) play an essential role in this active process, using several distinct suppressive mechanisms. A wide range of pathologies have been associated with altered Treg cell function. This is best exemplified by the impact of mutations of genes essential for Treg function and the associated autoimmune syndromes. This review summarizes the main features of different subtypes of Tregs and focuses on the clinical implications of their altered function in human studies. More specifically, we discuss abnormalities affecting FOXP3⁺ Tregs and Tr1 cells that will lead to autoimmune manifestations and/or allergic reactions, and the potential therapeutic use of Tregs.     

Increased microfilaments in hepatocytes and biliary ductular cells in cholestatic liver diseases

To assess the extent of microfilaments in cholestatic liver diseases we examined the cytoplasmic microfilaments in intrahepatic and extrahepatic cholestasis in man by electron microscopy. Study subjects were two patients with drug-induced intrahepatic cholestasis, three patients with intrahepatic cholestasis due to viral hepatitis, four patients with extrahepatic cholestasis due to stones of the common bile duct and two patients with primary biliary cirrhosis. Two biopsied specimens from patients without clinical or histological evidence of liver disease served as noncholestatic controls. The microfilaments in hepatocytes and biliary ductular cells were significantly increased in cholestasis compared with those in non-cholestatic controls. Well developed bundles of microfilaments were noted around the pericanalicular ectoplasm and seemed to be parallel to plasma membrane of the hepatocytes in cholestasis. In cholestasis, there were increased bundles of microfilaments around the periluminal region, lateral cell wall, and nucleus of biliary ductular cells. Two patterns of microfilaments bundles (fine microfilamentous network and spindle-shaped dense or clusters of microfilaments) were associated with cholestasis. The clustered form of microfilaments also seemed to be clearly associated with intracytoplasmic vacuoles containing bile salts. In conclusion, the increase of microfilaments in hepatocytes and biliary ductular cells may be the consequence of various forms of cholestasis. Further studies are needed to clarify the functional significance of increased microfilaments in cholestasis.     

Expression of cell adhesion molecules and their beta1 and beta2 integrin ligands in human liver peliosis

The expression of the following cell adhesion molecules and their beta1 and beta2 integrin ligands was investigated in the liver tissue from 3 patients with non-bacillar peliosis using light and electron microscope immunohistochemistry: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1), and very late antigen-4 (VLA-4). We found a parallel enhancement of the adhesion molecules expression in the dilated sinusoids and cavities in all 3 cases with peliosis. Mononuclear blood cells were detected in the sinusoids and sometimes perisinusoidally. These cells were mainly ICAM-1-, LFA-1-, and VLA-4-positive. At the ultrastructural level, ICAM-1-positive immune deposits were observed on the membrane of sinusoidal endothelial cells, Kupffer cells, and hepatocytes. The expression of cell adhesion molecules on liver sinusoids in peliosis is probably triggered by factors released from damaged endothelial cells and hepatocytes. The prevalence of the ICAM-1/LFA-1 and VCAM-1/VLA-4 patterns of mononuclear blood cell/sinusoidal cell interactions could support the macrophage-induced or lymphocyte-induced type of liver injury. PECAM-1 was also included in the non-specific immune response in peliosis. The presence of erythrostasis or thrombosis in liver sinusoids could participate in the induction of adhesion molecule expression in peliosis.     

气体信息分子与前列腺的生理病理过程

20世纪 6 0年代 ,发现用阿托品 (atropine ,ATR)阻断胆碱能神经 ,用胍乙啶 (guanethidine ,GUA)阻断肾上腺素能神经后 ,刺激消化道的一些神经 ,可引起消化道平滑肌舒张 ,这些神经当时被认为是非肾上腺素能和非胆碱能神经 (nonadrenergicandnoncholin ergicnerves ,NANC)。NANC神经释放何种递质尚不清楚。 1980年 ,Furchgott和Zawadzki发现许多血管扩张剂作用于血管内皮细胞 ,使其释放一种血管内皮舒张因子 (endothelium -derivedrelaxingfactor ,E DRF) ,使血管舒张[1] 。上个世纪 80年代末 ,国际生物学界一件令人瞩目的成就是证明…     

内毒素刺激人脐静脉内皮细胞免疫相关分子的表达

目的了解内毒素（LPS）刺激活化人脐静脉内皮细胞（HUVEC）后,与免疫相关的膜分子和细胞因子表达及变化情况,以探讨LPS激活内皮细胞后对免疫应答可能的影响。方法胰蛋白酶法分离培养人脐静脉内皮细胞,用RT-PCR观测未刺激和用LPS刺激的内皮细胞HLA-DR,CD80、CD86、B7-H1、B7-H2、B7-H3、B7-H4、B7-DC、HVEM、TR6、LTβR、LIGHT、OX40、OX40L等免疫相关分子的mRNA表达情况;用流式细胞仪技术检测CD40、CD137、ICAM-1蛋白的表达情况;ELISA检测细胞因子IL-6、IL-8、TNF-α、IFN-γ的含量。结果①RT-PCR结果显示,未经刺激的人脐静脉内皮细胞表达B7-H2、B7-H3、TR6、LTβR,并在LPS刺激后表达上调;B7-DC、HUVEM虽呈组成性表达,但在LPS刺激后未见变化;B7-H1、B7-H4仅在内皮细胞上为诱导表达;而CD80、CD86、LIGHT、HLA-DR、OX40无论刺激与否均未表达。②流式细胞仪检测证实其细胞表面表达少量CD137、CD40及ICAM-1,LPS刺激后其表达水平明显提高;③ELISA检测发现,内皮细胞在未激活状态下就能够分泌IL-6、IL-8和TNF-α,且LPS刺激后提高其分泌量。结论人脐静脉内皮细胞组成性表达多种免疫相关分子,LPS激活内皮细胞可以显著上调其表达。人脐静脉内皮细胞由于缺少CD80、CD86的共刺激信号,不能活化初始T细胞而只能向活化及记忆性T细胞提供共刺激信号在调节特异性免疫应答的过程中,可能会起到负调控的作用。