乙型肝炎免疫应答的研究进展

HBV感染后的转归依赖于病毒因素和免疫系统之间的平衡。病毒因素包括初始感染剂量、病毒复制动力学和扩散能力。免疫系统因素包括：动力学、特异性、体液和细胞免疫应答的持久性．以及其它非抗原特异性效应器机制如天然免疫应答的激活和细胞因子产生。对土拨鼠的研究结果提示慢性化表现在感染后出现低免疫应答的动物上．伴低水平细胞因子产生和严重程度较轻的急性肝炎^[1]，提示初始免疫应答的强弱是确定感染后转归的关键因素。

氟烷性肝炎免疫应答中特异性抗原的促淋巴细胞增殖作用

目的 探讨豚鼠氟烷性肝炎免疫应答中特异性抗原 (TFA GSA抗原 )刺激淋巴细胞增殖的作用。方法 雄性Hartley豚鼠 30只 ,随机分为实验组 (H组 )和对照组 (C组 ) ,每组又分 3个亚组 ,各 5只。H组 :在 4 0 %O2 (用N2 平衡 )下吸入 1%氟烷 ,持续 4小时 ,其中H1组只吸入 1次 ;H2 组间隔 4 2天后再吸入 1次 ,共吸入 2次 ;H3 组再间隔 4 2天再吸入 1次 ,共吸入 3次。C组 :只吸入4 0 %O2 (用N2 平衡 ) ,持续 4小时 ,其中C1组只吸入 1次 ;C2 组间隔 4 2天后再吸入 1次 ,共吸入 2次 ;C3 组间隔 4 2天再吸入 1次 ,共吸入 3次。人工合成特异性TFA GSA抗原。H1组和C1组在第35天 ,H2 组和C2 组在第 6 3天 ,H3 组和C3 组在第 10 5天分离得到淋巴细胞 ,分别加入不同浓度的TFA GSA抗原 (1 6、3 13、6 2 5、12 5、2 5 μg/ml) ,培养 7天。终止培养前 18小时加入氚标记胸腺嘧啶 (3 H TdR) ,通过淋巴细胞转化试验 (LTT) ,分析机体吸入氟烷后诱导免疫应答过程中 ,特异性抗原刺激淋巴细胞的增殖作用。结果 发现特异性抗原能诱导吸入氟烷豚鼠淋巴细胞增殖 ,其最低有效浓度随吸入氟烷次数的增加而降低。吸入次数少时 ,需要较大浓度的TFA GSA抗原 ;次数增加 ,其促淋巴细胞增殖的最佳浓度下降。

Immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in subjects over age of forty years and response of a booster dose among nonresponders

AIM:The study was initiated to evaluate the reactogenicity and immunogenicity of a recombinant hepatitis B vaccine in age group >40 years and to study the response of a single booster dose in primary non-responders to the hepatitis B vaccination. METHODS:A total of 102 volunteers without markers of hepatitis B infection (negative for HBsAg,anti-HBc antibody, HBeAg and anti-HBs antibody) received 20μg of recombinant HB vaccine intramuscularly at 0,1,and 6 months.Anti HBs titers were evaluated by a quantitative Elisa kit at 90 and 210 days.A booster dose of 20μg HB vaccine was given after 6 months of the 3^(rd) vaccine dose to the 15 non- responders and anti-HBs titers were measured after i month. RESULTS:Seroprotection (anti-HBs GMT^3 10 IU/L) was achieved in 85.3 % (87/102) volunteers.The mean GMT titers of the vaccine responders was 136.1 IU/L.Of the seroprotected individuals,there were 32.4% (33/102) hyporesponders (anti- HBs titers <10-99 mIU/ml) and 52.9% (54/102) were responders (anti-HBs titers >100 IU/L).All the non-responders (15/15) responded to a single dose of the booster dose of recombinant HB vaccine and their mean anti-HBs antibody titers were more than 100.5 mIU/ml after the booster dose. CONCLUSION:Recombinant hepatitis B vaccine offers good seroprotection in the age group >40 years and has a good safety profile.A single booster dose after 6 months in primary non-responders leads to good seroprotective anti-HBs antibody titers.However,larger population based studies are needed to evaluate the role of a booster dose in selected group of non-responders and whether such an approach will be cost effective.

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection.This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1000 mg-1 200 mg/daily) for 48 weeks,Blood samples were drawn at the beginning and the end of the therapy.Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS:At the beginning of treatment,TTV infection was detected in 10/15 (66.6%) of HCV-infected patients.Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients.Out of these 6 patients,4 (67%) became positive for TTV DNA after 6 months of therapy.Regarding HCV viremia,11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy,7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment.In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy,TTV DNA was detected as well.Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION:No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.

Network Biological Modeling:A Novel Approach to Interpret the Traditional Chinese Medicine Theory of Exterior-Interior Correlation Between the Lung and Large Intestine

Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.

Influence of the invasion of peripheral blood mononuclear cells by hepatitis B virus on immune response of the patients with chronic hepatitis B

Objective:To exploretheinfluenceof HBVinvasionintoperipheralbloodmononuclearcells(PBMC)on theimmuneresponseof patientswithchronichepatitisB.Method s:Thecytokinelevelsintheculturesupernatantof PBMCfrom56patientswithchronichepatitisB weredeterminedby ELISA,andPCRwasemployedto amplifythe HBVDNA.Results:Thelevelsof IFN-γinpatientswithhepatitisB waslowerthanthosetof thecontrol,butthe differencewasnotstatisticallysignificant,whilethelevelsof IL-4weresignificantlyhigherthanthoseof thecontrol(P<0.01).Theserumlevelsof HBVDNAwerenegativelycorrelatedwiththatof IFN-γin culturesupernatantsof PBMC.Thirty-fivepatientspositiveof HBVDNA inthePBMCswereidentifiedfrom56patientswithhepatitisB,andtheirIFN-γlevelprovedto be significantlydifferent.Conclusions:Th2cell-mediatedimmuneresponseis predo-minantin chronichepatitisB whichis associatedwiththechronicityof HBVinfection.HBVinvasionintothe PBMCsmayaffectTh1andTh2cell-mediatedimmuneresponseof thepatientswithchronichepatitisB.

粪便中脊髓灰质炎病毒IgA的ELISA检测方法比较

脊髓灰质炎是由脊髓灰质炎病毒Ⅰ、Ⅱ、Ⅲ型引起的传播广泛且危害极大的急性传染病。黏膜免疫在抗脊髓灰质炎免疫应答过程中颇为重要。局部黏膜分泌物（如唾液、肠液）中特异性IgA是机体接种口服脊髓灰质炎减毒活疫苗（OPV）或者自然暴露于脊灰病毒的一种重要免疫标志，同时也可作为评价黏膜免疫应答的主要指标。