乙肝疫苗接种无、弱应答者外周血单个核细胞培养上清IL-2水平及免疫复种效果

目的探讨IL-2水平与乙肝疫苗接种后免疫应答发生的关系以及复种卡介菌素和重组酵母乙肝疫苗对免疫失败人群的免疫效果。方法对1 071位57岁儿童进行乙肝标志物筛选,对乙肝疫苗接种无应答者首先接种免疫佐剂卡介菌素15次,再接种重组酵母乙肝疫苗,按0、1、3月方案进行免疫;随机选取抗-HBs阴性者21人和抗HBs≥10mIU/ml强应答组22人,抽取静脉血,分离外周血单个核细胞（PBMC）,用特异性抗原HBsAg和非特异性抗原植物血凝素（PHA）刺激培养,测定培养上清中的白细胞介素-2（IL-2）水平。结果1 071位儿童中HBsAg、抗-HBc和抗-HBs等全阴者127例,经复种免疫后,抗HBs阳性119例,阳转率93.70%（119/127）,平均几何滴度（GMT）为312.63 mIU/ml;在HBsAg或PHA刺激下,强应答组PBMC产生的IL-2水平均高于无、弱应答组（t=8.80和2.23,P均〈0.05）;PHA刺激的无、弱应答组和强应答组PBMC上清IL-2水平均高于HBsAg刺激组（t=5.70和4.38,P均〈0.05）。结论乙肝疫苗初免后抗-HBs为阴性者...更多按0、1、3月3针复种,可获得较好的免疫效果。乙肝疫苗无、弱应答者的PBMC可能存在着细胞免疫功能缺陷,由T细胞介导的细胞免疫功能低下可能是乙肝疫苗接种后无、弱应答发生的原因。     

2型糖尿病对乙肝疫苗接种免疫效果的影响及免疫对策分析

目的分析研究2型糖尿病对乙肝疫苗接种免疫效果的影响及免疫对策。方法该次研究中的观察组为该院2017年3月—2018年1月期间接收的接种乙肝疫苗的2型糖尿病患者,共选取20例,对照组为同期接种乙肝疫苗健康者,共20名。对上述两组接种疫苗效果、血清Th1与Th2细胞因子水平进行比较,分析不同免疫措施免疫效果加强情况。结果观察组患者血清抗HBs阳转率明显较对照组低,其无应答率则明显高于对照组(P0.05);观察组患者的IFN-γ、IL-2、IL-4均明显低于对照组,两组患者的IL-10水平比较(P0.05);皮下联合三角肌肌内注射法血清抗HBs阳转率明显较单纯三角肌肌内注射高(P0.05)。结论 2型糖尿病患者接种乙肝疫苗的免疫效果明显较健康者差,临床应当重视此类患者,将有效的免疫对策及时落实,以将患者的乙肝疫苗免疫效果提升。     

2型糖尿病患者对乙肝疫苗接种免疫效果的影响及免疫对策分析

目的研究分析2型糖尿病患者对乙肝疫苗接种免疫效果的影响,并探讨相应的免疫对策。方法选择2017年1月—2018年7月免疫预防接种中心进行乙肝疫苗接种的200例2型糖尿病患者与200名同期预防接种的健康志愿者,设置为观察组、对照组,两组均按照标准乙肝疫苗免疫接种程序完成乙肝疫苗接种,比较两组乙肝疫苗接种前后的血糖指标,并比较两组的血清抗HBs阳转率、抗HBs几何平均滴度、无应答率、血清Th1/Th2相关细胞因子水平。结果两组乙肝疫苗接种前、接种后的空腹血糖、餐后2 h血糖均无明显变化,差异无统计学意义(P0.05)。接种后,观察组的血清抗HBs阳转率、抗HBs几何平均滴度、IFN-γ、IL-2、IL-4均较对照组更低,差异有统计学意义(P0.05),其无应答率较对照组更高,差异有统计学意义(P0.05)。结论 2型糖尿病患者接种乙肝疫苗后的免疫应答状况不容乐观,2型糖尿病是影响成年人乙肝疫苗接种后免疫效果的主要因素之一,临床上应针对2型糖尿病患者进行乙肝疫苗加强免疫接种。     

广西地区人群乙肝疫苗无、弱应答与HLA-DRB1＊11等位基因的相关性研究

目的研究广西地区人群接种重组乙肝疫苗后无、弱应答与HIA—DRB1＊11等位基因的相关性。方法选取广西籍912名健康大学生,按0,1,6方案标准全程接种重组乙肝疫苗,接种半年后采血检测血清中抗．HBs水平。对首次检测抗．HBs〈10mIU／ml者再行接种重组乙肝疫苗20ug。4周后抗-HBs仍小于10mIU／ml的65人作为无、弱应答组,随机抽取首次检测抗-HBs〉10mIU／ml的中、强应答者96名作为对照组。应用PCR—SSP方法检测外周血HIA—DRB1＊11等位基因。结果HLA—DRB1＊11等位基因在无、弱应答组的携带率为16．92％,在中、强应答组的携带率为14．58％,两组比较无统计学意义（P〉0．05）。结论HIA．DRB1＊11等位基因频率与广西地区人群乙肝疫苗免疫无、弱应答无明显相关性。     

抗病毒治疗后HIV/AIDS病人对重组乙型肝炎疫苗的免疫应答

目的比较艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)抗反转录病毒治疗(ART)后,与健康者接种乙型肝炎(乙肝)疫苗后免疫应答的差异。方法健康对照者和ART后CD_4~+T淋巴细胞(简称CD_4细胞)计数均≥200个/μL的HIV/AIDS病人,分别在0、1、6个月肌内注射重组乙肝疫苗20μg,并在第3次疫苗注射后1个月检测抗乙肝病毒表面抗原抗体(抗-HBs)的水平,高于10 mIU/mL即为阳性。两组血清抗-HBs阳性率的比较采用卡方检验,抗-HBs效价的比较采用非参数检验中的Mann-Whitney检验。结果健康对照组19例,在第3次乙肝疫苗注射后1个月,抗-HBs阳性率94.7%(18例);HIV/AIDS病人组30例,在第3次乙肝疫苗注射后1个月,抗-HBs阳性率93.3%(28例);两组比较差异无统计学意义(P=1.000)。CD_4细胞≥350个/μL组HIV/AIDS病人23例,第3次乙肝疫苗注射后1个月,抗-HBs阳性率95.7%(22/23);CD4细胞350个/μL、200个/μL组7例,第3次乙肝疫苗注射后1个月,抗-HBs阳性率85.7%(6/7),两组比较差异无统计学意义(P=0.418)。CD_4细胞≥350个/μL组在第3次乙肝疫苗注射后1个月,血清抗-HBs效价中位数为251.24mlU/mL,CD_4细胞350个/μL、200个/μL组在第3次乙肝疫苗注射后1个月,抗-HBs效价中位数为237.6mlU/mL,两组比较差异无统计学意义(Z=-0.368,P=0.737)。所有接种者均未出现不良反应。结论 ART后,CD_4细胞计数≥200/μL的HIV/AIDS病人,对乙肝疫苗接种能获得相对较好的免疫应答,因此针对严重免疫抑制的HIV/AIDS病人,为提高接种乙肝疫苗的应答效果,较好的接种时机可选择在ART后且CD4细胞计数≥200个/μL时。     

TGF-β1对乙肝疫苗免疫应答的影响及与HLA-DRB1*15基因的关系

目的探讨TGF-β1对乙肝疫苗免疫应答的影响以及与HLA-DRB1*15基因的关系。方法选取完成重组乙型肝炎疫苗标准全程接种的健康大学生中抗-HBsS/N值10mIU/ml者77名为无、弱应答组,选取抗-HBsS/N值10mIU/ml者101名为中、强应答组,应用PCR-SSP进行HLA-DRB1*15等位基因的检测,采用ELISA法检测血清中TGF-β1水平。结果①无、弱应答组的HLA-DRB1*15基因表达频率为14.29%(11/77),低于中、强应答组的28.71%(29/101)(P=0.022);②无、弱应答组中TGF-β1的平均表达水平为(24.04±14.74)ng/ml,高于中、强应答组(17.80±14.42)ng/ml;差异有统计学意义(P=0.005);③HLA-DRB1*15阳性组TGF-β1平均表达水平为(17.81±17.38)ng/ml,阴性组为(21.28±14.00)ng/ml,差异无统计学意义(P=0.194)。结论①HLA-DRB1*15基因可能是促进人群乙肝疫苗免疫应答的相关基因;②TGF-β1的表达水平可能影响机体乙肝疫苗的免疫效果;③HLA-DRB1*15基因可能不是通过影响TGF-β1的表达水平来影响乙肝疫苗的免疫应答。     

CD150在成人乙型肝炎疫苗无应答者体外外周血单个核细胞中的表达

目的 了解信号转导淋巴细胞激活分子(SLAM)CD150在乙型肝炎(乙肝)疫苗无应答者体外外周血单个核细胞(PBMC)中的表达.方法 对2007年9月至2009年12月曾行乙肝疫苗接种、HBV标志物检测均阴性的202例患者进行标准程序再免疫,再接种后第7～12个月检测抗-HBs效价.根据抗-HBs效价判定无应答者18例(男11例,女7例);选取应答者18例(男9例,女9例)作为对照.采集无应答者与应答者静脉血18 mL,淋巴细胞分离液密度梯度离心法分离PBMC,流式细胞仪测定细胞膜表面分子CD150.采用SAS统计软件包进行t检验以及Spearman 秩相关检验.结果 乙肝疫苗免疫后,在特异性刺激剂rHBsAg作用下,PBMC中CD150的表达无应答者为(39.20±10.66)%,高于应答者的(23.73±12.41)%,差异有统计学意义(t=2.1947,P<0.05);CD3+CD4+细胞中CD150的表达无应答者为(49.64±11.94)%.亦高于应答者的(37.73±11.02)%,差异无统计学意义(t=1.7175,P>0.05).在非特异性刺激剂植物血凝素(PHA)作用下,PBMC中CD150的表达在无应答者为(39.21±7.37)%,高于应答者的(23.18±12.68)%,差异有统计学意义(t=2.2835,P<0.05).在特异性刺激剂rHBsAg作用下,CD150在PBMC及CD3+CD4+细胞中与抗体效价呈负相关(r=-0.726,P<0.05).结论 CD150可能在机体接种乙肝疫苗后的无应答者中发挥一定作用.

Abstract：

Objective To study the expression of signaling lymphocytic activation molecule (SLAM)CD150 in peripheral blood mononuclear cells(PBMCs)isolated from adult non-responders to recombined yeast gene hepatitis B vaccine.Methods A total of 202 cases were recruited.All these subjects had been immunized with recombined yeast gene hepatitis B vaccine for more than one standard scheme in two years(from Sep 2007 to Dec 2009)and remained negative for hepatitis B markers(HBsAg,anti-HBs,HBeAg,anti-HBe and anti-HBc).After recruitment,all 202 subjects received another standard scheme(0,1 and 6 month)revaccination.The blood samples were collected 7 months later after the first injection of revaccination to detect anti-HBs titer.The PBMCs were isolated from 18 adult non-responders(anti-HBs titer<10 mIU/mL)and 18 adult responders(antiHBs titer≥100 mIU/mL).CD150 expression on cell surface was analyzed by flow cytometry.SAS package was used for t test and spearman rank correlation analysis.Results After rHBsAg stimulation,the percentage of PBMCs expressed CD150 was significantly higher in non-responders (39.20%±10.66%)than responders(23.73%±12.41%)(t=2.1947,P<0.05).The same trend was also observed in rHBsAg stimulated C133+CD4+T cells,but the difference was not statistically significant(49.64%±11.94%vs 37.73%±11.02%)(t=1. 7175,P>0.05).After phytohaemagglutinin (PHA)stimulation,the percentage of CD150-positive PBMCs was also significantly higher in non-responders (39.21%±7.37%)than responders(23.18%±12.68%)(t=2.2835,P<0.05).CD150 expressions in both PBMCs and CD3+CD4+T cells were negatively correlated with anti-HBs titer after rHBsAg stimulation (r=-0.726,P<0.05).Conclusion Activation of CD150 may contribute to the non-response to hepatitis B vaccine.     

抗HBV特异性主动免疫治疗肝功能正常的慢性HBV感染5年随访

目的探讨抗HBV特异性主动免疫对肝功能正常的慢性HBV感染者的远期疗效。方法治疗组125例采用抗HBV特异性主动免疫治疗:乙型肝炎(乙肝)疫苗20μg、注射用重组人白细胞介素-220万U、沙格司亭75μg,分别行三角肌肌内注射,每月1次,12次为1个疗程。对照组75例,采用维生素B1200mg,注射方法同上。结果治疗组疗程结束时HBsAg、HBeAg阴转率与HBV DNA(<105copies/ml)例数分别为7(5.6%)、20(16.0%)及22(17.6%),明显高于对照组的0、4(5.3%)及3(4.0%)(P<0.05)。结论抗HBV特异性主动免疫对肝功能正常的慢性HBV感染者近期及远期均有一定的疗效。     

HBV标志阳性者配偶婚前紧急乙型肝炎免疫的效果

目的:观察快速乙肝疫苗接种方案对HBV标志阳性者配偶婚前紧急乙肝免疫的效果.方法:健康受试者分为2组.组1按快程序(d0,7,14接种),组2按标准程序(mo 0,1,6接种)三角肌内接种20μg CHO乙肝疫苗.在首针接种后1,3,7,12和24 mo分别检测抗-HBs滴度等.结果:组1全程接种完成率(93.3%)显著高于组2(64.6%)(P<0.01).首针接种后1,3 mo组1血清抗-HBs阳转率(86.7%和93.3%)显著高于组2(22.9%和45.2%,P<0.01);7-24 mo各时段2组接近,无显著差异;抗-HBs有效保护率组1(77.8%,84.4%)显著高于组2(4.2%,26.2%,P<0.01);血清抗-HBs几何平均滴度(GMT)组1分别为109.5和112.8 IU/L,显著高于组2(19.6和40.1 IU/L,P<0.01).结论:d 0,7,14接种方案方便、全程接种完成率高、抗-HBs阳转率和GMT峰值高且出现早,对HBV标志阳性者配偶婚前紧急乙肝为理想的免疫方案.     

接种国产重组酵母乙肝疫苗200例免疫效果观察

乙肝疫苗接种已成为我国控制乙型肝炎的主要对策。现在新一代乙肝基因工程疫苗与血源疫苗相比 ,在生产来源安全性方面都有很大优越性。我们于1 998年 9月～ 2 0 0 1年 7月对本市 2 0 0例中专学校学生进行了国产重组酵母乙肝疫苗免疫效果观察。现报告如下。1　资料与方法在 1 998年入校的男女新生进行入校健康查体 ,在 HBV5项指标检测阴性者中选择 2 0 0例接种国产重组酵母乙肝疫苗 ,另 1 80例不接种疫苗者作为对照组。方法 :1 HBV指标检测 :抽取被检者空腹静脉血 2 ml,分离血清 ,采用 ELISA法检测 HBV表面抗原 (HBs Ag)、HBV核心抗…     

Recent advances in gut immunology

In recent years, there have been significant advances in our understanding of the mucosal immune system. In addition to unravelling some of the complexities of this system, including the discovery of completely new cells types, further insights into the three‐way interactions between mucosal immune cells, the intestinal epithelium and the microbial communities colonizing the GI tract promise to redefine our understanding of how intestinal homeostasis is maintained, but also how dysregulation of these highly integrated interactions conspires to cause disease. In this review, we will discuss major recent advances in the role of key immune players in the gut, including innate lymphoid cells (ILCs), mucosa‐associated invariant T cells (MAIT cells) and cells of the mononuclear phagocyte system (MPS), including how these cells interact with the intestinal epithelial and their crosstalk with components of the intestinal microbiota, and how these interactions shape host health.     

Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity

For prevention of Streptococcus pneumoniae (pneumococcus) infections in infancy, protein-conjugated capsular polysaccharide vaccines provide serotype-specific, antibody-mediated immunity but do not cover all of the 90+ capsule serotypes. Therefore, microbiologists have sought protective noncapsular antigens common to all strains. Alternatively, we investigated killed cells of a noncapsulated strain, which expose many such common antigens. Given to mice intranasally, this vaccine elicits antibody-independent, CD4+ T lymphocyte-dependent accelerated clearance of pneumococci of various serotypes from the nasopharynx mediated by the cytokine IL-17A. Such immunity may reproduce the natural resistance that develops in infants before capsular antibodies arise. Given by injection, the killed cell vaccine induces bifunctional immunity: plasma antibodies protective against fatal pneumonia challenge, as well as IL-17A-mediated nasopharyngeal clearance. Human testing of this inexpensive candidate vaccine by intramuscular injection is planned. Bacterial cellular vaccines are complex--a challenge for reproducibility. However, when several known protective antigens were deleted, the killed pneumococcal vaccine was still protective. This antigenic redundancy may prevent vaccine escape variants by recombinational loss, which is frequent in pneumococcus. Biochemically defined immunogens with bifunctional activity have also been devised. These immunogens are three-component conjugates in which cell wall teichoic acid (a common antigen capable of T cell activation) is coupled to a genetic fusion of two common pneumococcal proteins: a protective surface antigen and a derivative of pneumolysin, which provides TLR4 agonist activity and induces antitoxic immunity. Such constructs induce accelerated clearance when given intranasally and induce both immune mechanisms when injected. The defined composition permits analysis of structure-function activity.     

动脉粥样硬化形成与发展中的自身免疫反应

关于动脉粥样硬化的发病机制,目前尚未完全阐述清楚。近年来的研究显示自身免疫反应在动脉粥样硬化形成和发展过程中具有重要作用。现就自身免疫反应在动脉粥样硬化形成和发展过程中的作用做一综述。     

Immune reaction and colorectal cancer: Friends or foes?

The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.     

免疫系统的衰老及其机制

免疫系统随着年龄的增加而功能退化,出现免疫系统衰老.免疫系统衰老与老年人群感染的易感性、疫苗的低效性、自身免疫性疾病增加以及肿瘤多发性密切相关.免疫系统衰老的特征表现为细胞介导的免疫功能下降以及抗体介导的体液免疫应答的降低.在衰老过程中,T细胞和B细胞功能的下降与先天性免疫系统功能的降低同时存在.本文就免疫系统随年龄衰老的改变及其内在机制进行综述.     

Role of autoimmunity in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis. The pathogenesis of PBC involves environmental factors, genetic predisposition and loss of immune tolerance. In recent years, it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC. In this study, the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.     

Conditional ablation of CD205+ conventional dendritic cells impacts the regulation of T-cell immunity and homeostasis in vivo

Dendritic cells (DCs) are composed of multiple subsets that play a dual role in inducing immunity and tolerance. However, it is unclear how CD205(+) conventional DCs (cDCs) control immune responses in vivo. Here we generated knock-in mice with the selective conditional ablation of CD205(+) cDCs. CD205(+) cDCs contributed to antigen-specific priming of CD4(+) T cells under steady-state conditions, whereas they were dispensable for antigen-specific CD4(+) T-cell responses under inflammatory conditions. In contrast, CD205(+) cDCs were required for antigen-specific priming of CD8(+) T cells to generate cytotoxic T lymphocytes (CTLs) mediated through cross-presentation. Although CD205(+) cDCs were involved in the thymic generation of CD4(+) regulatory T cells (Tregs), they maintained the homeostasis of CD4(+) Tregs and CD4(+) effector T cells in peripheral and mucosal tissues. On the other hand, CD205(+) cDCs were involved in the inflammation triggered by Toll-like receptor ligand as well as bacterial and viral infections. Upon microbial infections, CD205(+) cDCs contributed to the cross-priming of CD8(+) T cells for generating antimicrobial CTLs to efficiently eliminate pathogens, whereas they suppressed antimicrobial CD4(+) T-cell responses. Thus, these findings reveal a critical role for CD205(+) cDCs in the regulation of T-cell immunity and homeostasis in vivo.     

Hepatitis C virus-specific immune responses in noninjecting drug users

Noninjection drug use, although recognized as an emerging risk factor for acquisition of other blood-born pathogens, is still unconfirmed as a route of hepatitis C virus (HCV) transmission. Our goal was to measure HCV exposure and prevalence in noninjection drug users (NIDUs). Fifty-seven NIDUs were screened by extensive questionnaire to exclude prior injection drug use and evaluated for HCV-specific serologic and cellular immune responses. HCV-specific T-cell responses were measured using interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) assay with overlapping HCV peptides covering the entire HCV genome. Fifteen individuals who never used illicit drugs served as negative controls. Eleven people with no history of injecting drug use (19.3%) were HCV seropositive: seven with chronic HCV infection and four with previously resolved infection. Of 51 NIDUs with ELISpot results, HCV-specific cellular immunity was detected in 5 (9.8%). These responses were relatively weak and narrow. We did not find significant associations between HCV-specific immune responses and noninjection drug use practices. Subjects with HCV-specific immunity, however, were significantly more likely to have bought sex in the past 6 months, to have had more casual partners of the opposite sex in the last 6 months, and those partners were more likely to have ever injected drugs compared to subjects without HCV-specific immunity. In summary, we found serologic or cellular HCV-specific immune responses in 27.5% of NIDUs. Our results suggest that sexual behaviour associated with noninjection drug use might be a risk factor for HCV acquisition. Additional studies are needed to precisely determine the practices that lead to HCV exposure among this population.     

Pathogenesis of autoimmune hepatitis

The mechanisms underlying the pathogenesis of autoimmune hepatitis are not fully understood, though there is growing evidence that genetic predisposition, molecular mimicry and/or impairment of regulatory T-cells are involved in the initiation and perpetuation of the autoimmune liver attack. The histological picture of interface hepatitis, characterized by a dense portal mononuclear cell infiltrate, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of this condition. Liver damage is likely to be orchestrated by CD4(pos) T-cells recognizing an autoantigenic liver peptide. For autoimmunity to arise, the peptide must be presented by antigen-presenting cells to na?ve CD4(pos) T-helper (Th0) cells. Once activated, Th0-cells can differentiate into Th1-, Th2-, or Th17-cells, initiating a cascade of immune reactions that are determined by the cytokines they produce. Autoantigen recognition and the above effector mechanisms are opposed by regulatory T-cells, a cell subset numerically and functionally impaired in autoimmune hepatitis.