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1.
张锦涛  梁子婷  董亮 《病毒学报》2022,38(2):470-478
21世纪初,包括严重急性呼吸综合征冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)在内的高致病性冠状病毒对人类健康构成了巨大威胁。随着新型冠状病毒肺炎(COVID-19)在全球的暴发,冠状病毒尤其是能够引起严重下呼吸道感染的高致病性冠状病毒(HPCoVs)再次引起了人们的关注。在HPCoVs不断出现的大背景下,阐明其致病机制并控制感染过程中的宿主免疫对抵抗病毒感染,避免过度反应至关重要。在病毒感染过程中,多种天然免疫信号在冠状病毒感染过程发挥关键作用。本文就近年来出现的HPCoVs特征及其感染过程中天然免疫的应答情况作一综述,借此探寻重症感染患者炎症反应旺盛的原因并解释其临床表现,为进一步探寻精准治疗的潜在靶点。  相似文献   

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幽门螺杆菌感染可通过各种致黏膜炎症信号诱导宿主产生较强的免疫反应,但宿主免疫应答非但不能有效地清除感染,反而促进炎症反应而导致病情的加剧。本文综述了幽门螺杆菌感染所致宿主免疫应答以及该菌长期定居胃黏膜和致炎症的机制。  相似文献   

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鸡传染性支气管炎(Infectious Bronchitis,IB)一直是危害世界养禽业的最重要的疫病之一.IBV变异频繁,导致出现多种不同致病性毒株,不同致病性IBV的出现可能与其感染后免疫系统的激活有关.对IBV组织嗜性和感染后的免疫机制的研究对疫病防控具有重要意义.本研究为了探究IBV不同毒株组织嗜性和固有免疫应答之间的关系.将不同IBV毒株接种原代细胞、鸡胚、SPF鸡,进行各器官的组织嗜性鉴定,应用荧光定量的方法测定TLR3、TLR7、MAVS、MDA5、IFN-β和IFN-γ等细胞因子在SPF鸡的不同组织器官包括气管、肾、胃、肺、脾和法氏囊中mRNA的表达差异.结果表明,除-H52为已知疫苗毒株外,AH毒株对泌尿系统致病性强,TM毒株对消化系统有致病性.感染实验后显示,在气管中,AH感染组MDA5的mRNA表达显著下调,TM组IFN-β和IFN-γ的mRNA表达显著性上调,H52组MAVS与IFN-β表达上调;在肺脏中,AH组TLR3、TLR7、IFN-β和IFN-γ显著性上调,在TM组能看到MDA5和IFN-γ表达显著升高,H52组的TLR3、TLR7、MDA5、IFN-β和IFN-γ上调;在肾中,AH组和TM组IFNβ和TLR7表达下调,H52组TLR7、MAVS、IFN-β和IFN-γ表达上调;在腺胃中,AH组TLR7、MAVS﹑MDA5、IFN-β和IFN-γ表达上调,TM株IFN-γ表达上调,H52组TLR7表达显著性下调,MAVS、IFN-β和IFN-γ表达上调;在脾脏中,AH组MAVS表达上调,TM组TLR3、TLR7和MDA5表达显著性上调.H52组TLR7和IFN-γ的表达也显著提高;在法氏囊中,AH组各因子表达无显著性差异,TM组TLR7、MDA5和IFN-y表达上调,H52组中TLR3、TLR7、MAVS、MD)A5、IFN-β和IFN-γ表达均显著上调.不同组织嗜性的IBV毒株在各组织器官中各细胞因子表达量不同,不同组织嗜性毒株在固有免疫应答上存在差异且与免疫分子表达水平有相关性.本实验为不同IBV毒株感染机制、疫苗开发、病原与细胞相互作用的研究应用奠定理论基础.  相似文献   

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幽门螺杆菌(Helicobacter pylori,H.pylori)感染引起机体强的胃粘膜免疫应答,机体却无法对其进行完全根除,表明幽门螺杆菌具有逃避或破坏宿主免疫应答的特性。影响H.pylori逃避或破坏宿主免疫应答的因素或途径有很多,如肽聚糖的结构性修饰、H.pylori形态的改变、脂多糖抗原表位变化、IV型分泌系统、VacA和Treg细胞的免疫抑制作用、通过抑制吞噬细胞的吞噬作用和引起吞噬细胞的凋亡等等,本文就此作一综述,为以后对H.pylori的防御和治疗提供新的线索。  相似文献   

5.
乙型肝炎病毒变异与宿主免疫应答的研究进展   总被引:1,自引:0,他引:1  
分子生物学与免疫学的新进展使乙型肝炎病毒(HBV)的研究发生了革命的变化。由突变HBV所致不同类型的感染是由宿主免疫系统,干扰素(IFN)的反应和病毒基因型之间的复杂相互作用所致。本文从病毒变异与宿主免疫应答两方面综述了近年来HBV分子生物学研究中的新进展。  相似文献   

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禽坦布苏病毒(Avian Tembusu virus,ATMUV)是近年来在我国新发现的一种病毒,可感染多种蛋禽,感染动物临床特征为采食量下降,产蛋量骤减,甚至停产,感染后期呈神经症状,如腿和翅膀麻痹、共济失调等。ATMUV在我国多个省市地区流行,给我国甚至世界养禽业带来严重影响。固有免疫是机体抵抗病原感染的第一道重要防线,是机体与生俱来的抵御病原微生物的能力。适应性免疫是机体免疫系统在抗原刺激下产生特异性抗体及免疫效应细胞的过程,以建立针对某种病原微生物的抵抗力,是机体免疫系统的重要部分。本文将从禽坦布苏病毒诱导宿主固有免疫应答和适应性免疫应答两方面进行综述。  相似文献   

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沙门菌病(Salmonellosis)是全世界最普遍的食源性疾病之一,不仅对养殖业造成经济损失,还对人类安全构成威胁。禽沙门菌感染肠道后,可诱导肠上皮细胞表达多种TLRs和炎症反应的发生,在分泌的趋化因子作用下免疫效应细胞迁移到感染部位。细菌通过肠上皮细胞屏障后被巨噬细胞或树突状细胞吞噬,其中巨噬细胞是沙门菌的主要定殖场所。天然免疫系统将抗原递呈给淋巴细胞后,机体能够在2–3周内通过以Th1为主的免疫应答清除在肠道和深层组织中的沙门菌。而宿主特异性血清型鸡白痢沙门菌从肠道侵入后,在肝脾和其他器官中定殖,进而引发全身感染。早期感染阶段不会引起肠道炎症反应,主要诱导以Th2为主的免疫应答,而Th1型应答相对较弱,有利于鸡白痢沙门菌在机体内的持续存在和感染。本文围绕禽沙门菌的致病机理和免疫应答特性进行阐述,尤其对鸡白痢沙门菌免疫逃逸和持续载菌的特性进行深入分析,为禽沙门菌病的防控提供新靶标和新见解。  相似文献   

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念珠菌作为一类最常见的人类机会性致病菌,会导致重症和免疫功能低下患者的高发病率和死亡率。其自身有效的策略可入侵宿主并逃避宿主防御系统。而宿主对抗念珠菌的能力取决于天然免疫应答和适应性免疫应答。宿主体内大量免疫细胞和免疫分子相互协作针对侵入性的真菌做出反应。该文就宿主对念珠菌感染免疫应答机制作一综述。  相似文献   

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肠道菌群作为动物体内重要的组成部分,能够直接参与机体的免疫调控作用,促进机体免疫系统发育,维持正常免疫功能.同时,免疫系统对肠道菌群又有调控和制约作用.本文主要综述了肠道菌群的组成以及影响肠道菌群变化的因素,系统阐述了肠道菌群与疾病相互作用的机制,总结了肠道菌群在宿主感染与免疫应答中的作用,为开展肠道菌群参与机体免疫应...  相似文献   

11.
肿瘤细胞能够通过多种机制抵御免疫防御或药物的抗肿瘤作用.近年研究发现,外泌体能够直接介导癌症的进展和远端转移灶的形成.更为重要的是,在肿瘤免疫微环境中,肿瘤来源外泌体不仅能够抑制树突状细胞(DC)、巨噬细胞、T细胞、NK细胞等免疫细胞功能,还能促进骨髓来源的抑制性细胞(MDSC)、调节性T细胞(Treg)等的免疫抑制功能,进而降低抗肿瘤免疫应答过程,帮助肿瘤细胞逃避机体免疫细胞识别.本文将概述肿瘤外泌体及其携带的关键介质分子在介导肿瘤免疫逃逸和耐受过程中扮演的角色,并对这一研究领域的最新进展作一综述.  相似文献   

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A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γand IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.  相似文献   

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Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells.  相似文献   

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A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing t...  相似文献   

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Human cytomegalovirus (HCMV), a ubiquitous in humans, has a high prevalence rate. Young people are susceptible to HCMV infection in developing countries, while older individuals are more susceptible in developed countries. Most patients have no obvious symptoms from the primary infection. Studies have indicated that the virus has gradually adapted to the host immune system. Therefore, the control of HCMV infection requires strong immune modulation. With the recent advances in immunotherapy, its application to HCMV infections is receiving increasing attention. Here, we discuss the immune response to HCMV infection, the immune escape mechanism, and the different roles that HCMV plays in various types of immunotherapy, including vaccines, adoptive cell therapy, checkpoint blockade therapy, and targeted antibodies.  相似文献   

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Most tumours arise from a single normal cell through a sequential evolutionary process of mutation and selection. Tumours are initiated by escaping non‐immune surveillance, which includes defective DNA repair, epigenetic gene alternation, resistance to apoptosis and loss of intercellular contact inhibition. Tumour cells harbour mutations in a number of critical genes that provide selective advantages at various stages during the evolution of the tumour. The tumour cells that circumvent the tumour suppressor mechanisms of the non‐immune surveillance process are edited by the immune system, resulting in the selection of a resistant tumour variant. The selection of the tumour cell is further shaped by its interactions with cells and other factors in its microenvironment. Tumour evolution is thought to adhere to Darwinian principles by escaping both non‐immune (intrinsic) and immune (extrinsic) responses against self‐altered tumour cells. At end‐stage, tumours have escaped both non‐immune and immune surveillance with increased threshold of apoptosis. Combination therapy has been proposed, by exploring the non‐immune and immune suppressive nature of the tumour, and has been found to have a therapeutic efficiency on tumour regression as compared with monotherapies. The combination of immunotherapy and other different modalities, especially vaccines, with conventional anticancer therapies with optimized dosage and scheduling can offer synergistic antitumour effects. Here, we focus on the mechanism of tumour evolution and its implication in combination therapy.  相似文献   

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To evaluate the immunogenicity of inactivated SARS coronavirus (SARS-CoV), three groups of rabbits were immunized three times at 2-week intervals with inactivated vaccine + adjuvant, adjuvant, and normal saline respectively. Eight batchs of serum were sampled from the auricular vein at day 7 to day 51, and specific IgG antibody titers and neutralizing antibody titers were detected by indirect ELISA and micro-cytopathic effect neutralizing test. Antibody specificity was identified by proteinchip assay. Histopathological changes were detected by H&E staining. The results showed that, rabbits in the experimental group immunized with inactivated SARS-CoV all generated specific IgG antibodies with neutralizing activity, which suggested the inactivated SARS-CoV could preserve its antigenicity well and elicit an effective humoral immune responses. The peak titer value of specific IgG antibody and neutralizing antibody reached 1:40960 and 1:2560 respectively. In the experimental group, no obvious histopathological changes was detected in the H&E stained slides of heart, spleen, kidney and testis samples, but the livers had slight histopathological changes, and the lungs presented remarkable histopathological changes. These findings are of importance for SARS-CoV inactivated vaccine development. Foundation item: Joint funds of National Natural Science Foundation of China (U0632010); Program of Guangdong Provincial Key Lab of Bioengineering Medicine (51207026).  相似文献   

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To evaluate the immunogenicity of inactivated SARS coronavirus(SARS-CoV),three groups of rabbits were immunized three times at 2-week intervals with inactivated vaccine + adjuvant,adjuvant,and normal saline respectively.Eight batchs of serum were sampled from the auricular vein at day 7 to day 51,and specific IgG antibody titers and neutralizing antibody titers were detected by indirect ELISA and micro-cytopathic effect neutralizing test.Antibody specificity was identified by proteinchip assay.Histopathological changes were detected by H&E staining.The results showed that,rabbits in the experimental group immunized with inactivated SARS-CoV all generated specific IgG antibodies with neutralizing activity,which suggested the inactivated SARS-CoV could preserve its antigenicity well and elicit an effective humoral immune responses.The peak titer value of specific IgG antibody and neutralizing antibody reached 1:40960 and 1:2560 respectively.In the experimental group,no obvious histopathological changes was detected in the H&E stained slides of heart,spleen,kidney and testis samples,but the livers had slight histopathological changes,and the lungs presented remarkable histopathological changes.These findings are of importance for SARS-CoV inactivated vaccine development.  相似文献   

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