结肠炎大鼠结肠免疫功能的改变和褪黑素调节

目的:研究褪黑素(MT)对免疫性结肠炎大鼠结肠局部免疫功能的影响。方法:利用三硝基苯磺酸和乙醇复制大鼠免疫性结肠炎模型,设正常对照组、模型对照组、5-氨基水杨酸给药组(5-ASA,100mg·kg~(-1))和MT给药组(2.5,5.0,10.0mg·kg~(-1)),每天灌肠给药1次,从复制模型7d后开始至实验结束共21d。检测大鼠结肠组织白细胞介素(IL-1、IL-2)、肿瘤坏死因子(TNF-α)、一氧化氮(NO)、髓过氧化物酶(MPO)和丙二醛(MDA)水平;另制备模型对照组大鼠炎症结肠匀浆并加入脂多糖LPS,设阴性对照组、模型对照组、5-ASA给药组(终浓度为100μmol/L)和MT给药组(终浓度为0.01,0.1,1.0mmol/L)。取上清测IL-1、IL-2、TNF-α、NO、乳酸脱氢酶(LDH)、MPO和MDA水平。结果:模型对照组大鼠结肠中IL-1、IL-2、TNF-α、NO、MPO和MDA含量增多,MT可呈不同程度的抑制作用;模型对照组大鼠炎症结肠匀浆中IL-1、IL-2、TNF-α、NO、LDH、MPO和MDA含量显著增加,预先加入MT可明显降低IL-1、TNF-α、LDH、MPO和MDA含量,1.0mmol/LMT可明显抑制NO产生。结论:三硝基苯磺酸引起的结肠炎大鼠结肠存在明显免疫功能紊乱,MT可从不同水平调节结肠异常免疫功能减轻大鼠结肠炎症状。     

生物活性肽-Pm对小鼠免疫功能影响的探讨

中国图书分类号Ｒ３９２３３观察了生物性活肽Ｐｍ（简称ＢＡＰＰｍ）对正常及免疫功能低下小鼠免疫功能的影响,为临床防治提供适宜的免疫增强药物。１材料与方法小鼠,随机分为正常对照组、免疫低下组、免疫低下给药组;给药组动物由经食道喂入ＢＡＰＰｍ,连续...     

调节免疫应答在新型冠状病毒所致心肌损伤中的作用

新型冠状病毒(SARS-CoV-2)是2019年末在湖北武汉发现的第7种可以感染人类的冠状病毒,归为β属。临床统计发现该病毒常导致心肌损伤,且具有心血管基础疾病患者的感染风险更高,预后更差。目前新型冠状病毒对心肌损伤机制仍不明了。本文从新型冠状病毒与机体免疫系统相互关系阐述其对心肌损伤机制,并介绍相关的免疫治疗进展。     

钩端螺旋体疏水外膜蛋白(OmpL39)对豚鼠免疫功能影响的研究

目的研究钩体蛋白抗原的免疫保护力及其机制。检定纯化的强毒０１７钩体相对分子质量为３９×１０３的疏水外膜蛋白（ＯｍｐＬ３９）对豚鼠的免疫保护力。对免疫应答期豚鼠红细胞免疫功能的变化进行观察,以期对钩体基因疫苗的研制提供依据。方法用ＴＸ－１１４抽提钩体的不同蛋白成分,分三批对３６只豚鼠进行免疫保护力试验,检测红细胞免疫功能ＲＢＣ－Ｃ３ｂＲＲ、ＲＢＣ－ＩＣＲ、ＲＦＥＲ、ＲＦＩＲ的变化;用χ２检验、ｔ检验处理数据,进行分析。结果ＯｍｐＬ３９在豚鼠体内能产生高效价的显凝抗体（ＭＡＴ：１３２００）。ＲＢＣ－Ｃ３ｂＲＲ、ＲＢＣ－ＩＣＲ均明显升高（Ｐ＜０．０５）;红细胞免疫粘附因子促进率（ＲＦＥＲ）上升,抑制率（ＲＦＩＲ）下降,两者比值显著增大（Ｐ＜０．０５）。结论ＯｍｐＬ３９对豚鼠有有效的免疫保护力,在免疫应答期除增强体液免疫外,在提高红细胞免疫功能方面也起到了积极的作用     

脾氨肽口服冻干粉治疗小儿反复呼吸道感染的疗效及对免疫功能影响的观察

目的 探讨脾氨肽口服冻干粉治疗和预防小儿反复呼吸道感染(RRI)的临床效果.方法 将216例RRI惠儿随机分为对照组104例.治疗组112例.二组患儿在性别、年龄、临床表现无显著性差异.二组患儿在急性期均予抗感染、化痰、止咳、解痉、平喘及对症支持治疗等常规治疗.治疗组在常规治疗的基础上予以脾氨肽口服冻干粉治疗2个月,观察治疗后效果及治疗前后分别测定患儿T细胞亚群、免疫球蛋白等指标并观察其变化情况.结果 两组总有效率分别为51.9%和96.4%,有显著性差异(P<0.01),观察组的疗效优于时照组.观察组免疫学指标CD3、CD4、CD4/CD8、IgG及IgA均明显升高(P<0.01或P<0.05),CD8及IgM治疗前后无显著性差异(P>0.05).结论 脾氨肽口服冻干粉对治疗和预防小儿RRI有较好疗效.     

不同免疫途径对抗原肽修饰DC疫苗免疫效应的影响

目的探讨不同的免疫途径对抗原肽修饰树突状细胞(DC)疫苗免疫效果的影响。方法用鸡卵清蛋白(OVA)MHCⅠ限制性多肽SIINFEKL(OVAp257-264)包被小鼠骨髓来源的DC,通过皮下、腹腔、静脉或肌肉注射免疫小鼠,7天后行体内细胞毒性T淋巴细胞杀伤实验(InvivoCTL)分析CTL杀伤活性和细胞内IFN-γ染色(ICS)分析免疫小鼠脾脏CD8+细胞产生IFN-γ的情况。结果免疫7天后,InvivoCTL结果显示SIINFEKL修饰的DC皮下、腹腔、静脉或肌肉注射免疫小鼠其特异性CTL杀伤效应分别是37.3%±7.3%、61.0%±4.2%、56.9%±3.6%和10.8%±2.3%;ICS结果示四组小鼠产生IFN-γ的CD8+细胞占总CD8+细胞的比例分别是0.31%±0.07%、0.85%±0.12%、0.76%±0.14%和0.15%±0.04%。结论不同免疫途径可明显影响抗原肽修饰DC疫苗的免疫效应,其中腹腔注射诱发的抗原特异性CTL反应最强,静脉注射者次之,而皮下注射特别是肌肉注射较弱,提示通过腹腔注射DC疫苗可能是安全、高效的免疫途径。     

腹腔注射胶原蛋白肽增强糖皮质激素免疫抑制模型小鼠的免疫功能

目的观察腹腔注射胶原蛋白肽对糖皮质激素诱导的免疫抑制小鼠免疫功能的调节作用。方法采用糖皮质激素诱导的免疫抑制小鼠模型,连续7 d腹腔注射给予100、300、600 mg胶原蛋白肽/kg体质量。分别测量小鼠体质量、胸腺和脾脏质量,计算胸腺和脾脏指数;采用全自动血球计数仪检测外周血白细胞总数、中性粒细胞和淋巴细胞数、中性粒细胞和淋巴细胞百分比,采用流式细胞术检测CD4+/CD8+比值;采用MTT法检测刀豆蛋白A(ConA)诱导的脾脏T淋巴细胞增殖能力。结果与对照组相比,模型组小鼠中性粒细胞数及其百分比显著升高(P0.05),体质量、胸腺指数、脾脏指数、淋巴细胞数及其百分比、CD4+/CD8+比值、脾脏T淋巴细胞增殖能力显著降低(P0.05);腹腔注射胶原蛋白肽后,这些指标均向对照组水平恢复,并呈剂量依赖性关系;其中剂量最高600 mg/kg组的小鼠体质量、脾脏指数、淋巴细胞百分比、CD4+/CD8+比值显著高于模型组,中性粒细胞百分比显著低于模型组(P0.05),与对照组相比无显著差异。结论腹腔注射胶原蛋白肽能够增强小鼠的免疫功能。     

SARS冠状病毒S蛋白表位合成肽抗原性的研究

目的　研究SARS病毒合成肽疫苗。方法　根据目前已知SARS病毒的基因组序列及其编码的蛋白质 ,选择了SARS病毒编码的spike蛋白抗原表位蛋白质序列 ,运用计算机抗原表位预测技术 ,筛选抗原表位 ,以合成肽抗原表位。通过对SARS病人血清进行筛选确定与血清高交叉反应的 3个短肽 ,再合成多重抗原肽 (multipleantigenicpeptide ,MAP) ,与KLH偶联后免疫小鼠。结果　筛选的 3条与SARS病人血清反应强的肽 ,免疫小鼠均产生了高效价的抗体。结论　以合成肽为免疫原研究SARS病毒肽疫苗有着广阔前景。     

Phage displayed peptides recognizing porcine aminopeptidase N inhibit transmissible gastroenteritis coronavirus infection in vitro

Porcine aminopeptidase N (pAPN) is a cellular receptor of transmissible gastroenteritis virus (TGEV), a porcine coronavirus. Interaction between the spike (S) protein of TGEV and pAPN initiates cell infection. Small molecules, especially peptides are an expanding area for therapy or diagnostic assays for viral diseases. Here, the peptides capable of binding the pAPN were, for the first time, identified by biopanning using a random 12-mer peptide library to the immobilized protein. Three chemically synthesized peptides recognizing the pAPN showed effective inhibition ability to TGEV infection in vitro. A putative TxxF motif was identified in the S protein of TGEV. Phages bearing the specific peptides interacted with the pAPN in ELISA. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays confirmed the protective effect of the peptides on cell infection by TGEV. Moreover, the excellent immune responses in mice induced by the identified phages provided the possibility to develop novel phage-based vaccines.     

The effect of disgust on oral immune function

Disgust motivates avoidance of pathogen sources, but whether its role in disease avoidance extends into activating the immune system is unexplored. This was tested here by comparing oral immune markers before and after a disgust induction, relative to neutral and negative induction control groups. The disgust group, but not controls, revealed an oral inflammatory response, with increased salivary tumor necrotizing factor alpha and albumin, as well as a down-regulation of immunoglobulin A (SIgA) secretion. It has been hypothesized that disgust evolved in animals to clear toxins from the oral cavity by gaping and increased salivary flow. Our data suggest down-regulated SIgA secretion may be a vestige of this response so as to conserve protein, while the inflammatory reaction may reflect an adaptive response to disease threat, selectively triggered by disgust. The broader implications of these data for a discrete neuro-gut-immune axis are examined.     

人冠状病毒HKU1血清学检测方法的建立及其初步应用

目的 表达HCoV-HKU1的壳蛋白（N蛋白）及棘突蛋白（S蛋白）,建立检测血清中相应抗体的方法.方法 使用原核表达系统表达纯化HCoV-HKU1的N蛋白,转膜制条建立基于蛋白印迹的N抗体检测方法.构建HCoV-HKU1 S蛋白的真核表达质粒,转染细胞后,用间接免疫荧光（IFA）建立S抗体检测方法.利用已建立的N抗体和S抗体检测方法,检测了100份正常成人血清.结果 经Western Blot检测,S和N蛋白表达正确;利用已建立的血清学检测方法分析100份正常成人血清,其中HCoV-HKU1 S抗体的阳性率为47%,N抗体的阳性率为48哂,S抗体和N抗体均阳性的占总数的21%,双抗体均阴性的占总数的22%.S抗体和N抗体共同检测可获得74%的阳性检出率.结论 所建立的方法可用于HCoV-HKU1血清学分析,共同检测HCoV-HKU1 S抗体和N抗体可获得较好的检测结果.在正常成年中HCoV-HKU1抗体阳性检出率较高.     

SARS病毒S蛋白片段与细胞结合作用分析

目的研究SARS冠状病毒(SARSCoV)S蛋白片段与SARSCoV敏感细胞Vero的相互作用,明确S蛋白的受体结合位点。方法在E.coli中表达S蛋白第260～600位氨基酸(S260600)和397～796位氨基酸(S397796)片段,通过Westernblot对蛋白表达进行确认,用NiSepharose螯合层析对重组蛋白进行纯化。将纯化的S260600和S397796蛋白与Vero细胞4℃共同孵育1h后,先后与SARS患者血清及FITC标记的抗人IgG作用,通过流式细胞仪检测蛋白与细胞表面受体的结合情况。结果成功构建了原核表达质粒pET30a/S260600和pET30a/S397796,并表达、纯化出S260600和S397796重组蛋白。分别用SARS患者血清和抗6×His单克隆抗体进行Westernblot检测,证实重组蛋白得到正确表达。流式细胞仪分析显示S260600和S397796重组蛋白均可与Vero细胞发生结合,但S397796的结合力要弱于S260600。同时发现S260600重组蛋白与SARSCoV非敏感细胞NIH3T3细胞不能结合,进一步证明S260600重组蛋白与Vero细胞表面受体的结合是特异性的。结论重组蛋白S397796和S260600具有受体结合能力,尤其S260600包含了重要的受体结合位点,对进一步研究介导SARSCoV感染的细胞表面受体、开展疫苗和抗病毒药物的筛选均具有重要意义。     

Nutritional control of immunity: Balancing the metabolic requirements with an appropriate immune function

The immune system is a highly integrated network of cells sensitive to a number of environmental factors. Interestingly, recent years have seen a dramatic increase in our understanding of how diet makes a crucial contribution to human health, affecting the immune system, secretion of adipocytokines and metabolic pathways. Recent experimental evidence indicates that diet and its components are able to profoundly influence immune responses, thus affecting the development of inflammatory and autoimmune diseases. This review aims to discuss some of the main topics concerning the impact of nutrients and their relative composition on immune cell development and function that may be particularly important for regulating the balance between inflammatory and tolerogenic processes. We also highlight the effects of diet on commensal bacteria and how changes in the composition of the microbiota alter intestinal and systemic immune homeostasis. Finally, we summarize the effects of dietary compounds on epigenetic mechanisms involved in the regulation of several immune related genes.     

Assessing immune function by profiling cytokine release from stimulated blood leukocytes and the risk of infection in rheumatoid arthritis

Persons with rheumatoid arthritis (RA) suffer a high burden of infections, but currently no biomarkers are available to identify individuals at greatest risk. A prospective longitudinal study was therefore conducted to determine the association between the responsiveness of ex vivo cytokine production and 6-month risk of infections. Infections were identified by billing codes and validated by medical record review. At baseline, the release of 17 cytokines by peripheral blood mononuclear cells in response to stimulation, or media alone, was measured using multiplexed cytokine analysis. Production of IL-2, IL-8, IL-10, IL-17, TNF-α, IFN-γ, and GM-CSF, induced by various conditions, was significantly associated with the occurrence of infections. A multivariable prediction model based on these data provided new information on the risk of infection beyond standard assessments of disease activity, severity, and treatment. Future studies could utilize this information to devise new biomarkers for the prediction of infection in patients with RA.     

新冠病毒疫苗诱导的伴有血小板减少的免疫性血栓综合征的报告率

新冠肺炎疫情催生了新冠病毒疫苗的快速研发和应用,2020年年底以来国内外陆续有4类11款新冠疫苗已获批附条件紧急上市。上市前,这些疫苗的有效性和安全性评价都表现良好。但是疫苗上市后,在真实世界( real-world)随着接种剂次的增加,某些疫苗接种后陆续出现罕见的不良反应,引起了人们的广泛关注。在所有的不良反应中,尤...     

Ultrastructure of human nasal epithelium during an episode of coronavirus infection

The nasal epithelium from a young girl was examined by electron microscopy and found to be infected by coronavirus. Virions are seen within and outside the ciliated cells, but not outside or within the goblet cells or other cells of the nasal mucosa. Some virions are located near the microvilli, others in pockets in the apical cell membrane. The cytoplasm contains many small vesicles with a single virion, large apical vesicles containing hundreds of virions, and lysosome-like cytosomes with a moderate number of virions. Some viruslike particles devoid of an electron-dense interior are seen both in the cytosomes and extracellularly. Virus budding was observed in the Golgi apparatus but nowhere else in the cell. The ciliated cells seem not to be destroyed by the viruses, although in many cases the cilia are withdrawn into the cell body. The loss of cilia is likely to cause rhinorrhoea.     

2010-2012年南京市呼吸道冠状病毒流行病学特征分析

目的 分析2010年11月至2012年10月南京地区4个型别冠状病毒流行病学特征.方法 采集江苏省人民医院与南京医科大学第二附属医院流感样(influenza-like illness,ILI)病例咽拭子标本,并收集患者相关信息,利用RT-PCR方法进行检测,应用SPSS 17.0对数据进行统计分析.结果 1233例标本中,冠状病毒核酸阳性者共有115份(总阳性率9.33％),主要为229E型(36.52％,42/115)、OC43型(29.57％,34/115)与HKU1型(25.22％,29/115).2010-2012年不同年份间,冠状病毒229E型、HKU1型与NL63型阳性率有统计学差异(229E亚型:X2=18.072,P＜0.001;HKU1亚型:X2 =22.091,P＜0.001;NL63亚型:X2 =6.470,P=0.039).结论 南京地区冬季为冠状病毒流行高峰期,夏季为低谷期,春秋季小高峰趋势不明显.2010-2012年南京地区人呼吸道冠状病毒主要流行亚型为229E型、OC43型与HKU1型.不同年份冠状病毒主要流行亚型存在一定差异.     

Genetic alterations in the ageing immune system: impact on infection and cancer

The immune system, which is able to distinguish between self and non-self, is programmed to protect the organism from a huge spectrum of potential foreign invaders. Each T and B lymphocyte bears an antigen receptor of a single specificity, which is determined during development by a unique genetic mechanism that generates millions of different variants of the genes encoding the receptor molecules. When a particular antigen, such as a virus, is encountered, only those lymphocytes bearing the relevant receptors become activated and undergo massive clonal expansion. The expanded antigen-specific B cells produce antibodies, which neutralize free virus in the bloodstream, whereas the T cells, particularly the so-called CD8 T cells, actually kill cells that are infected with the virus. Once the infection is cleared, most of the expanded T cells undergo apoptosis, leaving a small number of memory cells to await future possible encounters with the same virus. During ageing, both latent and acute viral infections lead to increased morbidity and mortality, based, in large part, on the diminished ability of T cells to control the infection. To investigate the underlying mechanism of the T cell defects, we have analyzed the process of replicative senescence in human T cells. Our research has shown that following repeated stimulation with antigen in cell culture, the responding T cells eventually reach an irreversible state of cell cycle arrest, at which time they show loss of gene expression of a key T cell-specific signaling molecule required for proliferation, as well as reduced stress protein production, apoptosis resistance, shortened telomeres and inability to upregulate telomerase. Increased proportions of T cells with identical phenotypes are present in elderly individuals, suggesting that chronic/repeated stimulation of some T cells may lead to replicative senescence in vivo. Genetic modulation of this process may yield novel strategies to augment immune function in the elderly.