张家口地区献血者隐匿性乙肝病毒感染研究

目的:对张家口地区无偿献血者中隐匿性乙肝病毒感染情况进行流行病学调查,为当地血液安全筛查提供指导意义.方法:应用HBsAg ELISA检测试剂盒对回库无偿献血者标本进行检测;对血浆标本采用nested-PCR技术进行HBV核酸检测;对阳性标本进行HBVDNA序列分析.结果:在总计5498例次标本的检测中,共有5417例为HBsAg阴性;HBsAg阴性标本中nested-PCR方法检出13例HBV DNA阳性(0.24％,13/5417);测序结果显示隐匿性HBV感染者中C基因型所占的比例为61.5％(10/16),明显高于HBsAg阳性的HBV感染者(28.2％,11/39,P＜0.01).结论:张家口地区无偿献血者中存在较高比例的隐匿性乙肝病毒感染.     

330例乙肝病毒免疫标志物与HBV-DNA检测的关系探讨

目的 探讨乙肝病毒免疫标志物与HBV-DNA之间的相关关系,为临床诊断和确定治疗的方案疗效观察提供有价值的依据。方法 用ELISA法检测血清免疫标志物,荧光定量聚合酶链反应(PCR)HBV-DNA,并对其进行探讨。结果 HBsAg、HBeAg、HBcAb均阳性组,HBsAg、HBeAb、HBcAb均阳性组,HBsAb、HBeAb、HBcAb均阳性组,HBcAb阳性组,全阴组中,HBV-DNA阳性检出率分别为100％,61．3％,51．9％,15．4％,63％,12．5％,6．7％。结论 FQ-PCR检测乙肝病毒在体内感染和复制,对临床诊断,确定治疗方案和疗效观察有一定价值。     

乙肝免疫标志物与乙肝病毒核酸含量与肝功能的关系研究

目的:研究乙肝免疫标记物(HBV-M)与乙肝病毒脱氧核苷酸(HBV-DNA)载量与肝功能的关系。方法:检测104例乙肝患者HBs Ag、HBe Ag、HBc Ab、HBs Ab、HBe Ab5种HBV-M;用PCR法检测HBV-DNA含量;同时检测天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、胆碱酯酶(CHE)等肝功能指标,对三者关系采用Spearman相关性分析。结果:HBs Ag、HBc Ab、HBe Ag阳性组HBV-DNA阳性率及载量均大于其余组(P0.05);HBe Ag含量、ALT浓度与HBV-DNA载量均呈正相关(r=0.48,P0.05)、(r=0.36,P0.05);AST、CHE与HBV-DNA含量无明显相关性,但在无病毒载量与有病毒载量组之间AST比较有统计学意义(P0.05)。结论:HBV-M、HBV-DNA与肝功能之间有一定的相关性,但HBe Ag阴转不代表病毒复制停止,HBV-DNA也不能完全反应肝损害程度,临床应加大重视。     

具有饱和发生率和免疫响应的病毒感染模型的稳定性分析改进

通过构造Lyapunov函数,改进了具有饱和发生率和免疫响应的病毒感染数学模型的稳定性分析,得到了当病毒感染的基本再生数R_01时,无病平衡点全局渐进稳定;当R_01时,在一定条件下,免疫耗竭平衡点和持续带毒平衡点全局渐近稳定的结论.     

具免疫时滞的HIV感染模型动力学性质分析

讨论了一类具免疫时滞的HIV感染模型.分析了未感染平衡点的全局渐近稳定性,给出了感染无免疫平衡点及感染免疫平衡点局部渐近稳定的充分条件.数值模拟结果表明,当易感细胞生成率的取值使得基本再生数满足平衡存在的条件且低于某一临界值时,时滞对平衡点的稳定性没有影响;若大于该临界值,随着时滞增大,稳定性开关发生,平衡点不稳定,出现一系列Hopf分支,最终表现为周期波动模式.     

乙肝病毒感染导致Mrell下调及基因组断裂

[目的]乙肝病毒的持续感染与肝细胞癌的发生密切相关.本文探讨了乙肝病毒感染后导致宿主蛋白Mrell的变化,并研究这种蛋白的变化可能导致肝癌发生的机制.[方法]本文通过Westernblot检测了乙肝病毒感染HL7702细胞及肝癌组织标本的Mrell蛋白的变化,并且通过RNA干涉的方法干扰了Mrell的表达,用连接介导PCR检测基因组的变化.[结果]本研究发现乙肝病毒感染细胞导致Mrell表达下调,肝癌组织也可以发现Mrell表达下调;下调Mrell表达可以导致细胞基因组的断裂增多.[结论]HBV感染导致Mrell表达下调导致基因组不稳定,这可能与HBV感染导致细胞恶性转化相关.     

登革病毒感染的免疫与免疫病理的研究进展

登革病毒感染是世界上热带与亚热带地区一个严重的公众卫生健康问题,本文综述了登革病毒感染后机体免疫的改变,并从抗体、Ｔ细胞激活及细胞因子过量释放方面探讨了登革出血热（ＤＨＦ）／登革休克综合征（ＤＳＳ）的发病机理。     

具有周期传染率的SIR传染病模型的周期解

考虑了具有周期传染率的SIR流行病模型,定义了基本再生数^-R0=β／（μ＋γ）,分析了该模型的动力学性态,证明了当^-R0〈1时无病平衡点是全局稳定的;^-R0〉1时,无病平衡点是不稳定的,模型至少存在一个周期解。对小振幅的周期传染率模型,给出了模型周期解的近似表达式,证明了该周期解的稳定性,最后做了数值模拟,结果显示周期解可能是全局稳定的。     

斑马鱼用于病原菌感染与免疫及自噬的研究进展

斑马鱼作为一种脊椎动物模型,是研究病原菌感染与免疫的理想对象,目前已成功构建了多种细菌感染斑马鱼模型。由于其在通体透明的幼鱼阶段只有天然免疫系统发育完善,因此利用斑马鱼研究天然免疫具有许多优势,且能避免获得性免疫的干扰。自噬作为一种高度保守的胞内降解过程,是天然免疫的重要部分,可通过Toll样受体或黏膜免疫系统等参与对细菌的应答。目前,对斑马鱼自身发育需要及清除母体残留物所进行的自噬已进行了初步研究。最近细菌感染斑马鱼的体内自噬研究模型已成功构建,这对体内异源自噬机制的研究意义重大。本文就近年来利用斑马鱼模型研究病原菌感染与免疫及自噬的进展作一综述。     

CXCR3通过调控Notch1信号影响乙肝病毒X蛋白对肝癌细胞周期和迁移的作用

乙肝病毒X蛋白（Hepatitis B virus X protein,HBx）是乙肝病毒诱导肝癌进展的关键因子,其能够影响肝癌细胞周期和促进其迁移。已知趋化因子受体3(chemokine CXC motif receptor 3,CXCR3)在乙型肝炎病毒肝癌中发挥促进作用,目前尚不清楚CXCR3在HBx诱导的肝癌细胞中的作用。因此,本研究探讨下调CXCR3对HBx诱导的肝癌细胞周期进展和迁移作用及机制。肝癌细胞Huh7分成对照组,pcDNA组（转染阴性对照载体）,pcDNAHBx组（转染HBx过表达载体）,pcDNA-HBx+si-NC组（共转染HBx过表达载体、siRNA对照的）,pcDNA-HBx+si-CXCR3组（共转染HBx过表达载体、CXCR3 siRNA的）,pcDNA-HBx+si-CXCR3+Jagged1组（共转染HBx过表达载体、CXCR3 siRNA,Notch1信号激活剂Jagged1处理）,测定细胞中HBx、CXCR3、神经性钙黏附素（Neural cadherin,N-cadherin）、基质金属蛋白酶-9(Matrix metalloprotease...     

Simulation and Prediction of the Adaptive Immune Response to Influenza A Virus Infection

The cellular immune response to primary influenza virus infection is complex, involving multiple cell types and anatomical compartments, and is difficult to measure directly. Here we develop a two-compartment model that quantifies the interplay between viral replication and adaptive immunity. The fidelity of the model is demonstrated by accurately confirming the role of CD4 help for antibody persistence and the consequences of immune depletion experiments. The model predicts that drugs to limit viral infection and/or production must be administered within 2 days of infection, with a benefit of combination therapy when administered early, and cytotoxic CD8 T cells in the lung are as effective for viral clearance as neutralizing antibodies when present at the time of challenge. The model can be used to investigate explicit biological scenarios and generate experimentally testable hypotheses. For example, when the adaptive response depends on cellular immune cell priming, regulation of antigen presentation has greater influence on the kinetics of viral clearance than the efficiency of virus neutralization or cellular cytotoxicity. These findings suggest that the modulation of antigen presentation or the number of lung resident cytotoxic cells and the combination drug intervention are strategies to combat highly virulent influenza viruses. We further compared alternative model structures, for example, B-cell activation directly by the virus versus that through professional antigen-presenting cells or dendritic cell licensing of CD8 T cells.Understanding how the immune system combats influenza virus infection and how the virus can affect the immune system is crucial to predicting and designing prophylactic and therapeutic strategies against the infection (58). Antigenic shift and antigenic drift alter the degree to which preexisting immunity can control the virus. These factors also influence whether different arms of the adaptive immune system can cross-react against new strains of the virus. For example, shifts of the hemagglutinin (HA) and neuraminidase (NA) protein sequences limit the ability of antibodies to neutralize new variants of the virus and may make cross-reactive T-cell responses to conserved viral proteins more important. Other viral proteins, such as NS1, affect both the induction of type I interferon as well as the susceptibility of infected cells to interferon-mediated inhibition of viral gene expression (43). The efficiencies of viral replication and cell-to-cell viral spread are altered by mutations in the viral matrix and polymerase genes, while the survival of infected cells can be altered by the viral PB1-F2 protein. These attributes are influenced by mutations in the viral matrix (50, 51) and polymerase (30, 69) genes, while the survival of infected cells can be altered by the viral PB1-F2 protein (17). The multigenic aspect of influenza virus pathogenesis makes experimental prediction difficult and time-consuming. Computer simulation tools would be useful to independently dissect the potential contribution and relative importance of each factor or to investigate unexpected scenarios that are difficult to replicate experimentally.Mathematical models and computer simulations have been widely used to study viral dynamics and immune responses to viral infections, such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses (SIV), lymphocytic choriomeningitis virus (19, 55, 60, 61), and influenza A virus (3, 7, 8, 13, 34, 35, 52). More complex compartmental models of the immune system (4, 23) and models incorporating differential delay equations (21, 48, 68) have been used to better reflect the time that cells reside in a particular compartment or the duration of transit between compartments. In this study, we sought to develop a two-compartment mathematical model to assess the individual contributions of antigen presentation and activation of naïve T and B cells by antigen-presenting cells (APC), CD4 T-cell help, CD8 T-cell-mediated cytotoxicity, B cells, and antibody to control influenza A virus (IAV) infection and to explore the influence of anatomical location. We developed a model which represented published experimental findings on primary influenza virus infection. More importantly, the model was used to explore alternative structures for interactions between virus and immune cells, for example, comparing virus kinetics when antigen delivery and immune cell priming occurred through direct interaction of virus and immune cells or through a cellular intermediate. The model predicts that, under some circumstances, changes affecting antigen presentation more strongly impacted viral kinetics than other viral or immune factors (28, 73, 75, 78). This model highlights the importance of the assumptions used to synthesize a model and gaps in our understanding of the immune response regulating primary influenza virus infection. We discuss the implications of these findings for future influenza virus research and theories of influenza virus virulence based on influenza virus-immune system interactions.     

细胞自噬在病毒感染与免疫调节中的作用机制

细胞自噬(autophagy)是一种主要由溶酶体介导的降解通路,作为细胞维持内环境稳态的一种保护性机制,不仅通过将长寿命蛋白和衰老细胞器降解为小肽或氨基酸为细胞提供再生资源,而且也可作为防御机制抵抗病原微生物感染和寄生. 自噬缺失与许多疾病如癌症、心血管疾病等的发生关系密切,在机体生理、病理过程中发挥重要作用. 本文拟就细胞自噬与病毒感染、机体免疫的关系加以综述,以期为研究细胞自噬的发生、参与机体免疫、发挥抗病毒感染作用及其分子机制提供参考,也为进一步研究抗病毒治疗的靶标提供新思路.     

肝脏固有免疫系统对肠源性感染的免疫应答与免疫耐受机制

肝特殊的解剖结构及生理特征使其成为暴露肠源性抗原的主要器官。由于肝具有独特的固有免疫系统,在正常情况下,肝分布多种致耐受的抗原提呈细胞,对持续性表达或递呈于肝的肠源性抗原物质,诱发针对该抗原的系统性免疫耐受,避免肝受到不必要的免疫损伤。当炎症发生及肝脏固有免疫系统活化时,则通过免疫效应细胞及免疫效应因子对肠源性病原体发挥强烈地免疫应答以控制感染。该过程形成机制的研究对肝功能的理解及肝性疾病的预防与治疗至关重要。本文就肝固有免疫系统对肠源性感染的免疫应答与免疫耐受形成机制作一综述。     

Quantitative Analysis of Immune Response and Erythropoiesis during Rodent Malarial Infection

Malarial infection is associated with complex immune and erythropoietic responses in the host. A quantitative understanding of these processes is essential to help inform malaria therapy and for the design of effective vaccines. In this study, we use a statistical model-fitting approach to investigate the immune and erythropoietic responses in Plasmodium chabaudi infections of mice. Three mouse phenotypes (wildtype, T-cell-deficient nude mice, and nude mice reconstituted with T-cells taken from wildtype mice) were infected with one of two parasite clones (AS or AJ). Under a Bayesian framework, we use an adaptive population-based Markov chain Monte Carlo method and fit a set of dynamical models to observed data on parasite and red blood cell (RBC) densities. Model fits are compared using Bayes'' factors and parameter estimates obtained. We consider three independent immune mechanisms: clearance of parasitised RBCs (pRBC), clearance of unparasitised RBCs (uRBC), and clearance of parasites that burst from RBCs (merozoites). Our results suggest that the immune response of wildtype mice is associated with less destruction of uRBCs, compared to the immune response of nude mice. There is a greater degree of synchronisation between pRBC and uRBC clearance than between either mechanism and merozoite clearance. In all three mouse phenotypes, control of the peak of parasite density is associated with pRBC clearance. In wildtype mice and AS-infected nude mice, control of the peak is also associated with uRBC clearance. Our results suggest that uRBC clearance, rather than RBC infection, is the major determinant of RBC dynamics from approximately day 12 post-innoculation. During the first 2–3 weeks of blood-stage infection, immune-mediated clearance of pRBCs and uRBCs appears to have a much stronger effect than immune-mediated merozoite clearance. Upregulation of erythropoiesis is dependent on mouse phenotype and is greater in wildtype and reconstitited mice. Our study highlights the informative power of statistically rigorous model-fitting techniques in elucidating biological systems.     

高致病性冠状病毒感染导致宿主免疫应答异常

近二十多年,全球范围内先后爆发了由严重急性呼吸综合征冠状病毒（severe acute respiratory syndrome coronavirus,SARS-CoV）、中东呼吸综合征冠状病毒（middle east respiratory syndrome coronavirus,MERS-CoV）和严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2,SARS-CoV-2）3种高致病性冠状病毒导致的疫情。这3种高致病性冠状病毒感染通常伴随着免疫系统功能失调,临床表现有淋巴细胞减少症、细胞因子风暴、急性呼吸系统窘迫综合征,甚至多器官衰竭而导致死亡。揭示高致病性冠状病毒在免疫应答中的作用机制,对于预防与控制冠状病毒感染具有重要意义。本文总结了SARS-CoV、MRES-CoV和SARS-CoV-2的进入机制和受体特征、固有免疫应答和适应性免疫应答失调方面的研究进展,强调了高致病性冠状病毒与宿主免疫应答之间的复杂相互作用,以期为防治冠状病毒感染提供参考。