警报素家族研究进展

警报素最早在2004年提出,是一类可应答于危险因子,对固有免疫细胞具有趋化和激活作用,可激发和促进适应性免疫应答的内源性生物介质。目前公认的警报素家族成员主要来自防御素家族,抗菌肽家族,嗜酸粒细胞衍生神经毒素和高迁移率族蛋白等。在炎症或损伤因素的刺激下,警报素能够迅速地从储存部位释放。警报素可以通过促进抗原的摄取、处理和呈递来增强对抗原特异性免疫反应的诱导,是一类可增强免疫活性的佐剂。对警报素家族深入研究将有助于阐明其在免疫系统中的地位,并可能为免疫治疗提供新的手段或靶点。     

警报素家族研究进展

警报素最早在2004年提出,是一类可应答于危险因子,对固有免疫细胞具有趋化和激活作用,可激发和促进适应性免疫应答的内源性生物介质.目前公认的警报素家族成员主要来自防御素家族,抗菌肽家族,嗜酸粒细胞衍生神经毒素和高迁移率族蛋白等.在炎症或损伤因素的刺激下,警报素能够迅速地从储存部位释放.警报素可以通过促进抗原的摄取、处理和呈递来增强对抗原特异性免疫反应的诱导,是一类可增强免疫活性的佐剂.对警报素家族深入研究将有助于阐明其在免疫系统中的地位,并可能为免疫治疗提供新的手段或靶点.     

警报素IL-33及其与疾病的关系

随着功能基因组学和生物信息学的深入研究,白细胞介素1(IL-1)家族的新成员不断被发现,人们对其功能的研究也越来越深入。在哺乳动物,IL-1家族至少有11个成员:IL-1F1/IL-1α、IL-1F2/IL-1β、IL-1F3/IL-1Ra、IL-1F4/IL-18、IL-1F5/IL-36Ra、IL-1F6/IL-36α、IL-1F7/IL-37、IL-1F8/IL-36β、IL-1F9/IL-36γ、IL-1F10/IL-38和IL-F11/IL-33,针对IL-1β、IL-1Ra及IL-18的中和活性单克隆抗体或重组蛋白已被批准成功应用于多种临床疾病的治疗。IL-33是IL-1家族的新成员,可刺激不同细胞因子的产生,诱导Th2应答,参与抗感染免疫及炎症反应,近年来,已成为白细胞介素研究领域中关注的热点。现就有关IL-33的结构和产生、生物学功能以及IL-33与不同疾病的关系进行综述。     

小鼠初次及再次体液免疫应答测定及多抗甲素的作用

溶血素测定法是近几年广泛用于测定小鼠特异体液免疫反应的一种简便方法。我们从小鼠尾静脉取微量血连续测定溶血素,在同一小鼠测定初次及再次免疫应答的循环溶血抗体动态过程及多抗甲素对初次及再次免疫应答的作用。方法:实验小白鼠(昆明种,本院繁殖,雌雄兼用,体重25±3g)。以SRBC4×10~8(ip)初次免疫后31天,以等量SRBC(ip)再     

开胃素A在猪一些器官内的分布

目的：研究苏钟猪一些器官内开胃素(或增食因子)A(orexin A)的分布。方法：免疫组织化学法。结果：开胃素A免疫阳性细胞分布于猪睾丸、肾上腺、胰腺、小肠、甲状腺和胸腺等部位,睾丸间质、胰岛和小肠的粘膜固有层有大量免疫阳性细胞存在,而在肾上腺皮质、甲状腺和胸腺等部位仅有少量免疫阳性细胞分布。结论：猪一些器官内开胃素A的分布与人和其他动物的基本相似。首次报道了开胃素A在甲状腺和胸腺的分布,反映了开胃素在种系发生上的保守性,也说明存在种间差异。     

环孢素A亲合素—Cyclophilin研究进展

环孢素A亲合素(Cyclophilin,CyP)广泛存在于生物体内,是细胞内环孢素A (Cy-closporin A,CsA)的受体,具有催化加速蛋白质折叠和转运等生物学功能。CyP与CsA结合抑制了钙离子、钙调素(Calmodulin,CaM)依赖的神经钙蛋白(Calcineurin,CN)的磷酸酶活性,阻断IL-2等T细胞增殖必需的一些细胞因子的转录,介导CsA免疫抑制作用。CyP在自身免疫性疾病和器官移植排斥研究中具有应用价值。     

循环淋巴细胞回家机制研究进展

淋巴细胞回家(Iymphocyte homing)是关于循环淋巴细胞回至淋巴器官的一个现象。近年来,对淋巴细胞回家的研究,有许多突破性进展,这对淋巴细胞免疫功能研究,无疑是很重要的。 本文将从三方面介绍其主要内容:(1)回家受体(homing receptor)和居住素(addressin),主要涉及同回家有关的粘附分子;(2)     

AT1受体短肽主动免疫自发性高血压大鼠对血压和心血管重塑的影响

目的观察血管紧张素Ⅱ的Ⅰ型(AT1)受体细胞外的不同肽段主动免疫自发性高血压大鼠(SHR)对血压、心脏及血管的影响.方法2月龄SHR,随机分成5组,以合成的AT1受体胞外3个多肽片段分别免疫,其余2组为氯沙坦灌胃组(10 mg/(kg·d),标记为SHR-L)和对照组(SHR-C).同龄Wistar大鼠免疫干预同SHR,对照组用免疫佐剂.ELISA法检测抗体滴度,大鼠尾动脉血压计测量血压.试验结束检测心脏及左心室重量、肠系膜三级动脉中层及内径和组织病理变化、心肌超微病理变化.结果SHR 2月龄血压开始升高,所有免疫组动物均产生针对特定短肽的抗体.ATR12181免疫组SHR收缩压于免疫后一个月降低,并持续至实验结束(145.42±8.46 mmHg,n=7),与SHR-C(197.00±7.70 mmHg,n=7,P＜0.05)相比明显降低,与SHR-L(139.28±17.19 mmHg,n=7,P＞0.05)相比无显著性差异;而ATR12185和ATR10014免疫组SHR收缩压无明显变化.与SHR-C相比,ATR12181免疫组心脏/体重比(4.66±0.50 mg/g vs 5.16±0.11 mg/g,P＜0.05)和左心室/体重比(3.64±0.45 mg/g vs 4.19±0.07 mg/g,P＜0.05)均显著降低;而ATR12181免疫组与SHR-L心脏/体重比(4.41±0.60 mg/g)及左心室/体重比(3.50±0.31 mg/g)相比无显著性差异,P＞0.05,肠系膜三级动脉中膜厚度/管腔半径及中膜面积/管腔面积降低.Wistar大鼠各组免疫前后均产生相应抗体,收缩压无明显变化,心脏及血管未见病理变化.结论用ATR12181主动免疫SHR,可降低SHR血压,减轻心脏重量,逆转心肌和动脉重塑;ATR12181主动免疫Wistar大鼠后未见心脏及血管病理变化.     

orexin A和orexin 1型受体在新生大鼠与成年大鼠延髓分布的比较

本文研究orexinA(OXA)和orexin 1型受体(OX1R)在新生大鼠与成年大鼠延髓的分布及比较。新生(1～5d)和成年(6～8周)SD大鼠,取其延髓,采用免疫组织化学方法和图像分析技术,观察OXA和OX1R在新生与成年SD大鼠延髓的分布。结果显示,OXA免疫反应阳性纤维和OX1R免疫反应阳性细胞在新生和成年SD大鼠延髓内有广泛分布,主要分布在延髓腹外侧区(ventrolateralmedulla,VLM)和舌下神经核(hypoglossalnucleus,XII)。在这两个区域,新生大鼠组的OX1R免疫反应阳性细胞的相对光密度值均低于成年大鼠组(P<0.001)。结果表明随着大鼠发育成熟,OX1R表达水平增加,可能与其生理功能完善有关。OXA免疫反应纤维和OX1R免疫反应阳性细胞在延髓的VLM和XII的表达提示可能与心血管和呼吸等活动的调节有关。     

大蒜素上调节β防御素3的表达

目的:探索大蒜素与β防御素3(HBD3)的关系及其在人体抗感染的免疫机制。方法:采用含大蒜素培养液(5 mg/L)培养肺癌A549细胞,通过RT-PCR、Western blot及免疫荧光染色等方法检测HBD3在不同培养时间后表达量的差别。结果:大蒜素作用第4小时HBD3的mRNA表达量增加,第12小时HBD3的蛋白表达量增加。结论:通过本研究可以推断,大蒜素除本身的杀菌作用外,对人体自身主动免疫防御能力的影响调节也是其发挥抗菌作用的重要机制。     

Dendritic cells associated with plasmablast survival

A subset of myeloid dendritic cells is described which is associated with the ability of splenic and lymph node plasmablasts to survive and differentiate into plasma cells. Plasmablast-associated dendritic cells (PDC) are CD11c(high), DEC-205(-) and unlike conventional dendritic cells do not associate with T cells. The following findings suggest a requirement for PDC if plasmablasts are to differentiate to plasma cells. First, when large numbers of B cells are recruited into antibody responses and plasmablasts outgrow the PDC stroma, only those associated with PDC survive and differentiate into plasma cells. Conversely, if the number of PDC is increased by ligating their CD40, more plasmablasts survive on the expanded PDC stroma and differentiate into plasma cells. Finally, in T cell-deficient mice, the plasma cells that develop atypically in the T zones in response to thymus-independent antigens are associated with ectopic PDC.     

GB (guanidinobenzoatase) cell surface protease and serum inhibitors in colorectal neoplasia.

Cell surface proteases and their inhibitors are functionally related to the invasive properties and metastatic potential of tumour cells. Epithelial cells of the colorectal mucosa possess a cell surface protease referred to as guanidinobenzoatase (GB), which is similar, if not identical, to plasminogen activator. GB exists in isoenzymatic forms, one of which is associated with epithelial cells of normal colorectal mucosa and of adenomatous polyps, whilst another isoenzymatic form is associated with colorectal adenocarcinoma cells. Normal serum contains inhibitor proteins which recognize the isoenzymatic form of GB found on normal and adenomatous polyp epithelial cells but this inhibitor does not recognize the isoenzymatic form of GB associated with adenocarcinoma cells. The fluorescent probe 9-amino-acridine locates cells possessing active GB in frozen sections of colorectal mucosa. A technique is described which enables colorectal carcinoma cells to be highlighted by fluorescence microscopy whilst normal epithelial cells are distinguished by their lack of fluorescence. This is of biological and possibly diagnostic significance.     

Activation of extracellular regulated kinases is required for the increase in airway epithelial permeability during leukocyte transmigration

The goal of this study was to determine whether the extracellular regulated kinases (ERK1/2) are involved in leukocyte transmigration across airway epithelium and the associated changes in epithelial permeability. In vitro, we used formyl-methionyl-leucyl-phenylalanine (fMLP) to induce migration of HL-60 cells (a human leukocyte cell line) across sheets of polarized Calu-3 airway epithelial cells and also to induce migration of human neutrophils across primary cultures of cow tracheal epithelial cells. In both systems, leukocyte migration decreased transepithelial electrical resistance (R(te)), increased epithelial permeability to albumin (P(alb)), and increased ERK1/2 phosphorylation in epithelial cells. Leukocyte migration and the associated changes in R(te), P(alb), and ERK1/2 phosphorylation were inhibited by calphostin C, a blocker of protein kinase C (PKC), and by PD98059 (a blocker of ERK1/2). Leukocyte transmigration in rat tracheas in vivo was induced with fMLP, and was associated with increased P(alb) and phosphorylation of epithelial ERK1/2. Again, migration and the associated changes were inhibited by luminal PD98059 or calphostin C though neither agent affected rat leukocyte migration in Boyden chambers in vitro. We conclude that PKC and ERK1/2 pathways are activated in airway epithelial cells during migration of leukocytes and are important regulators of airway epithelial permeability.     

肿瘤相关免疫抑制细胞的免疫逃逸作用机制

肿瘤能够通过多种机制有效逃避机体免疫系统监视,肿瘤相关树突状细胞（TADC）、髓系来源抑制细胞（MDSC）、肿瘤相关巨噬细胞（TAM）等在肿瘤免疫逃逸过程中能够诱导免疫抑制反应。虽然由TADC、MDSC和TAM介导的免疫抑制机制还不完全明了,但是最近的研究表明肿瘤相关因子激活的细胞内信号传导途径可以调节细胞内代谢、细胞因子的产生和共刺激分子及共抑制分子的表达,由此产生免疫抑制作用。     

Human MHC Class I Antigens are Associated with a 90-kDa Cell Surface Protein

Human MHC class I proteins are expressed on almost all nucleated cells as a heavy chain (about 45 kDa) non-covalently associated with beta 2-microglobulin (12 kDa). In this report we show that MHC class I (MHC-I) proteins can also be associated with a 90-kDa protein in the cell membrane. Surface-radiolabelled cells were treated with dithiobis succinimidyl propionate (DSP) in order to preserve multimer protein complexes during cell lysis. The lysates were immunoprecipitated and analysed by SDS-PAGE and autoradiography. Immunoprecipitation of human MHC-I proteins co-precipitated another protein of about 90 kDa in molecular weight-p90. p90 was coprecipitated from all the MHC-I expressing cells tested: U937, Raji, Molt-4 and IFN-gamma treated K562, but not from untreated, MHC-I negative K562. A 90-kDa protein was also co-precipitated with MHC-I from fresh peripheral blood mononuclear cells (PBMC). Furthermore, p90 was coprecipitated by different MoAbs to the MHC-I heavy chain or beta 2-microglobulin, but not by control antibodies. Two additional co-precipitating proteins at 34 kDa and 28 kDa were seen in MHC-I precipitates from Raji cells. Our results suggest that MHC-I proteins and the 90-kDa protein are associated in the cell membrane, probably by a close but weak, non-covalent interaction. Two additional cell surface proteins at 34 kDa and 28 kDa seem to be MHC-I associated on Raji Burkitt's lymphoma cells.     

Endogenous lipid antigens for invariant natural killer T cells hold the reins in adipose tissue homeostasis

The global obesity epidemic and its associated co‐morbidities, including type 2 diabetes, cardiovascular disease and certain types of cancers, have drawn attention to the pivotal role of adipocytes in health and disease. Besides their ‘classical’ function in energy storage and release, adipocytes interact with adipose‐tissue‐resident immune cells, among which are lipid‐responsive invariant natural killer T (iNKT) cells. The iNKT cells are activated by lipid antigens presented by antigen‐presenting cells as CD1d/lipid complexes. Upon activation, iNKT cells can rapidly secrete soluble mediators that either promote or oppose inflammation. In lean adipose tissue, iNKT cells elicit a predominantly anti‐inflammatory immune response, whereas obesity is associated with declining iNKT cell numbers. Recent work showed that adipocytes act as non‐professional antigen‐presenting cells for lipid antigens. Here, we discuss endogenous lipid antigen processing and presentation by adipocytes, and speculate on how these lipid antigens, together with ‘environmental factors’ such as tissue/organ environment and co‐stimulatory signals, are able to influence the fate of adipose‐tissue‐resident iNKT cells, and thereby the role of these cells in obesity and its associated pathologies.     

Immunoelectron Microscopic Localization of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Smooth Muscle Cells from Morphologically Normal and Atherosclerotic Human Arteries

Vascular wall fibrinolytic system proteins are believed to play a pivotal role in atherogenesis. Tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) influence persistence of luminal thrombi and proteolysis of extracellular matrix, respectively. The major physiologic inhibitor of t-PA and u-PA is plasminogen activator inhibitor type 1 (PAI-1). All three of these fibrinolytic system proteins have been detected in vascular endothelial cells, smooth muscle cells, and macrophages by light microscopic immunohistochemistry. This study was undertaken to delineate, by immunoelectron microscopy, the loci of PAI-1 in smooth muscle cells from intact morphologically normal and atherosclerotic human arteries as well as in isolated and cultured smooth muscle cells from arteries. In intact vessels, PAI-1 immunoreactivity was associated with contractile filaments in cells in both normal and atherosclerotic tissues. Lipid-laden smooth muscle cells in atherosclerotic vessels were mainly of the synthetic phenotype and displayed lesser amounts of PAI-1 associated with rough endoplasmic reticulum and contractile filaments. Isolated smooth muscle cells exhibited either a contractile or synthetic phenotype. In the cells with a contractile phenotype, PAI-1 was associated with the contractile elements, whereas in the cells with a synthetic phenotype, the PAI-1 was associated predominantly with elements of the endoplasmic reticulum. Because PAI-1 is associated predominantly with contractile filaments in smooth muscle cells, the net amount of immunodetectable PAI-1 appears to be greater in contractile compared with synthetic phenotype cells.     

Immunoelectron Microscopic Localization of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Smooth Muscle Cells from Morphologically Normal and Atherosclerotic Human Arteries

Vascular wall fibrinolytic system proteins are believed to play a pivotal role in atherogenesis. Tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) influence persistence of luminal thrombi and proteolysis of extracellular matrix, respectively. The major physiologic inhibitor of t-PA and u-PA is plasminogen activator inhibitor type 1 (PAI-1). All three of these fibrinolytic system proteins have been detected in vascular endothelial cells, smooth muscle cells, and macrophages by light microscopic immunohistochemistry. This study was undertaken to delineate, by immunoelectron microscopy, the loci of PAI-1 in smooth muscle cells from intact morphologically normal and atherosclerotic human arteries as well as in isolated and cultured smooth muscle cells from arteries. In intact vessels, PAI-1 immunoreactivity was associated with contractile filaments in cells in both normal and atherosclerotic tissues. Lipid-laden smooth muscle cells in atherosclerotic vessels were mainly of the synthetic phenotype and displayed lesser amounts of PAI-1 associated with rough endoplasmic reticulum and contractile filaments. Isolated smooth muscle cells exhibited either a contractile or synthetic phenotype. In the cells with a contractile phenotype, PAI-1 was associated with the contractile elements, whereas in the cells with a synthetic phenotype, the PAI-1 was associated predominantly with elements of the endoplasmic reticulum. Because PAI-1 is associated predominantly with contractile filaments in smooth muscle cells, the net amount of immunodetectable PAI-1 appears to be greater in contractile compared with synthetic phenotype cells.     

CD57 expression by T cells in the female genital tract of HIV-zx1 infected women

Despite an influx of T cells to the cervix during HIV infection, genital T cells are not associated with control of HIV shedding. CD57 expression by T cells has been associated with enhanced migratory potential and CD57+ T cells have been shown to accumulate in tissues during the late stages of HIV disease. We investigated the impact of HIV-infection and clinical status on the expression of CD57 by T cells from the female genital tract in 13 HIV-infected and 5 uninfected women. We found that cervical and blood-derived T cells expressed similar frequencies of CD57. The frequency of CD57 expression by cervical or blood T cells was not associated with clinical status (CD4 counts). No impairment in IFN-γ production by CD57+ T cells from the genital tract was observed. We conclude that increased T cell senescence does not appear to be a hallmark of genital mucosal HIV-1 infection.     

Marasmius oreades lectin induces renal thrombotic microangiopathic lesions

The present studies demonstrate that infusion of a type B specific lectin derived from the mushroom Marasmius oreades (MOA) into mice binds selectively to the glomerular endothelial cells via surface carbohydrate moieties resulting in cell injury and death associated with platelet-fibrin thrombi. This selective MOA binding to the endothelial cells can be abrogated by a sugar specific for the carbohydrate sequence. Hemolytic-Uremic Syndrome (HUS) and the closely associated Thrombotic Thrombocytopenic Purpura (TTP) are diseases associated with widespread microvascular injury in various organs. Clinically, these diseases are associated with microangiopathic hemolytic anemia and thrombocytopenia. The kidney glomerulus is a primary target of this microvascular injury. There are many underlying etiologies including bacterial toxins. Experimentally, such toxins injure endothelial cells in vitro but in vivo studies have failed to reproduce the characteristic renal pathology. We suggest that MOA-induced glomerular microangiopathic injury could be used to study the pathophysiology of endothelial cell injury as related to glomerular microangiopathic injury.