复发性生殖器疱疹细胞免疫与治疗的相关性研究

目的检测复发性生殖器疱疹患者治疗前、后外周血T淋巴细胞亚群,观察治疗效果,并探讨机体细胞免疫的相关作用机理。方法复发性生殖器疱疹患者口服泛昔洛韦250mg,每天3次,连服5天,同时给予胸腺五肽1mg肌注,每天1次,15次为一疗程,共4个疗程。采用流式细胞仪检测52例复发性生殖器疱疹患者治疗前、后T淋巴细胞亚群（CD3^＋、CD4^＋、CD8^＋、CD4^＋/CD8^＋）,并与40例健康对照组进行比较。结果治疗组与健康对照组相比外周血CD3^＋、CD4^＋及CD4^＋／CD8^＋下降,CD8^＋升高,两组间差异有统计学意义（P〈0．01）。经抗病毒药物与免疫调节剂联合治疗2个月后,外周血CD3^＋、CD4^＋及CD4^＋／CD8^＋回升,而CD8^＋下降,治疗前、后差异有统计学意义（P〈0．01）。治疗前每例年平均发作4．5次,治疗后每例年平均发作1．5次,治疗前、后差异有统计学意义（P〈0．05）。结论复发性生殖器疱疹患者存在细胞免疫功能紊乱,抗病毒药物与免疫调节剂联合应用能改善患者的细胞免疫功能紊乱状况,降低生殖器疱疹复发率。     

共聚物-1直接免疫MPTP模型小鼠保护多巴胺能神经元

目的探讨共聚物-1(copolymer-1,Cop-1)直接免疫对小剂量1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)持续注射C57BL/6J小鼠黑质多巴胺(dopamine,DA)神经元保护作用的影响。方法雄性C57BL/6J小鼠分为MPTP模型组、造模后Cop-1免疫组、造模时Cop-1免疫组、造模前Cop-1免疫组、Cop-1免疫组和正常对照组。MPTP模型组动物仅接受MPTP注射,造模后Cop-1免疫组在MPTP连续注射7d后接受Cop-1免疫;造模时Cop-1免疫组在第1次MPTP注射后立即接受Cop-1免疫;造模前Cop-1免疫组在接受Cop-1免疫7d后开始注射MPTP,Cop-1免疫组仅接受Cop-1抗原免疫,正常对照组动物仅接受0.9%氯化钠注射液注射。MPTP连续注射24d后处死动物,取脑、脾。脑切片酪氨酸羟化酶免疫组化定量分析黑质DA神经元数;高效液相色谱法(high performance liquidchrom atography,HPLC)分析纹状体DA及其代谢产物含量;苏木精-伊红染色法(hematoxylin-eosin staining,HE)观察脾病理学变化;分离造模后Cop-1免疫组、造模时Cop-1免疫组、造模前Cop-1免疫组和Cop-1免疫组动物脾脏并进行Cop-1致敏淋巴细胞培养。结果与正常对照组相比,MPTP模型组、造模后Cop-1免疫组、造模时Cop-1免疫组、造模前Cop-1免疫组动物脾脏HE染色未见明显差异。与Cop-1免疫组相比,造模后Cop-1免疫组、造模时Cop-1免疫组、造模前Cop-1免疫组均出现大量Cop-1致敏淋巴细胞。黑质DA神经元定量分析显示,与正常对照组比较,持续低剂量MPTP注射使模型对照组黑质DA神经元减少了65.13%,造模后Cop-1免疫组、造模时Cop-1免疫组、造模前Cop-1免疫组黑质DA神经元分别减少了31.68%、27.55%和28.29%,各组DA神经元数明显高于模型对照组(P=0.000,P=0.000,P=0.000)。HPLC法测定纹状体内DA及其代谢产物含量结果显示,与正常对照组相比,模型组DA及其代谢产物含量明显减少。造模后Cop-1免疫组、造模时Cop-1免疫组、造模前Cop-1免疫组类似,但均明显高于模型组。结论在C57BL/6J小鼠慢性MPTP模型中,持续低剂量MPTP注射对小鼠的免疫器官脾的破坏不明显,Cop-1直接免疫可有效对抗MPTP毒性,保护黑质-纹状体系统的DA神经元。     

老年慢性阻塞性肺疾病急性期患者自然免疫缺陷与免疫干预研究

目的探讨老年慢性阻塞性肺疾病（COPD）患者急性期自然免疫功能的缺陷,并研究免疫干预治疗的作用。方法采用随机的方法将70例老年COPD住院患者分成干预组35例、对照组35例,另设老年健康对照组20例。患者入院后行常规检查治疗,老年干预组加用口服的非特异免疫调节药匹多的莫德（pidotimod）,观察30d,前15d,口服匹多的莫德,2次/d,2片/次（400mg/片）,后15d维持量,1次/d,2片/次,分别于第1天、第30天用流式细胞仪检测患者外周血CD14、CD158b、HLA-DR的改变,同时观察第10天时临床症状的改善情况。结果干预组、对照组、健康对照组最终纳入分析患者分别为30、28、20例。干预组、对照组外周血CD14、CD158b、HLA-DR参数均较健康对照组低,差异均有统计学意义（P〈0.05）。在常规治疗一致的前提下,加用匹多的莫德的干预组上述免疫参数在治疗30d时均明显升高,差异有统计学意义（P〈0.05）。第10天老年干预组的临床症状如咳嗽、咳痰、肺部湿啰音的改善均较对照组明显,差异有统计学意义（P〈0.05）。结论老年COPD在急性期发作期间自然免疫功能低下。加用非特异性免疫调节剂匹多的莫德（Pidotimod）片后,可改善自身的免疫功能,同时加快了临床症状的恢复。     

老年肺癌患者细胞免疫功能变化及意义

目的：测定老年肺癌患者外周血淋巴细胞表达水平,以期探讨老年肺癌患者的细胞免疫功能状态和临床意义。方法：采用流式细胞术检测老年肺癌患者及健康老年人外周血淋巴细胞表达,评价老年肺癌患者细胞免疫功能状态。结果：老年肺癌组CD3、CD4、CD4/CD8比值、NK细胞较对照组及老年健康组显著降低,差异有统计学意义（P〈0.05）。CD19细胞在各组间差异无统计学意义。结论：对老年肺癌患者细胞免疫功能的监测,有助于对病情及治疗的综合评估。     

帕瑞昔布联合吗啡术后静脉镇痛对胃癌患者淋巴细胞亚群和自然杀伤细胞活性的影响

目的观察帕瑞昔布联合吗啡术后静脉镇痛对胃癌患者淋巴细胞亚群和自然杀伤细胞(NK细胞)的影响。方法选择胃癌根治术患者40例,随机分为帕瑞昔布联合吗啡镇痛组(PM组,n=20)和吗啡镇痛组(M组,n=20)。两组患者均接受相同的麻醉方法。术毕分别用帕瑞昔布联合吗啡和单纯吗啡行静脉术后镇痛,采用视觉模拟评分法(VAS)镇痛评分评价镇痛效果,并分别于麻醉前、术毕、术后24h及术后48h抽取静脉血,用流式细胞仪检测T淋巴细胞亚群CD3+、CD4+、CD8+、CD4+/CD8+比值及NK细胞(CD16+、CD56+/CD45+)的变化。结果两组患者术后VAS评分比较差异无统计学意义(P>0.05);两组患者CD3+、CD4+淋巴细胞在术毕、术后24h及48h均较麻醉前明显降低(P<0.05),两组患者的NK细胞(CD16+、CD56+/CD45+)、CD4+/CD8+在术毕及术后24h也低于麻醉前(P<0.05)。CD8+在各时点变化差异无统计学意义(P>0.05)。与M组相比,PM组在术后24hNK细胞(CD16+、CD56+/CD45+)、CD3+、CD4+、CD4+/CD8+明显增高(P<0.05);PM组在术后48hNK细胞(CD16+、CD56+/CD45+)、CD4+/CD8+已恢复到麻醉前水平(P>0.05),而M组仍处于较低水平(P<0.05)。结论帕瑞昔布联合吗啡和单纯吗啡术后镇痛都取得良好的镇痛效果,但前者更有利于胃癌患者术后细胞免疫功能的恢复。     

Ⅰ型干扰素与细菌感染

干扰素( IFN)是免疫反应中重要的细胞因子.根据IFN作用受体的不同,IFN通常分为Ⅰ型IFN(主要包括IFN-α、IFN-β)和Ⅱ型IFN(IFN-γ),Ⅰ型IFN主要通过IFN受体A(IFNAR)介导机体抗病毒反应.近年研究表明,Ⅰ型IFN在机体抗细菌感染中也起着重要作用.文中着重对Ⅰ型IFN信号通路介导的宿主免疫在利斯特菌、链球菌、结核杆菌、炭疽芽孢杆菌、军团菌、铜绿假单胞菌等细菌感染中的作用作一综述.     

Immune safety of a novel oncolytic mutant M1 after administration In Vivo

The aim of this study was to evaluate the safety and efficiency of a novel,oncolytic adenovirus mutant M1 administered in conjunction with immunosuppressive agents.Animal models were established by administering purified M1 either intravenously or retroperitoneally.At different time points,blood samples were taken from the mice for testing of liver and renal function.Microscopic examination of the liver was performed to observe pathological changes.Immunohistochemical analyses were used to evaluate the expression of the adenovirus in the liver.Lymphocyte recruitment to the liver and the activation of adenovirus specific T cells were also analyzed.No signs of general toxicity were observed,but transient increases in ALT and Scr were observed following the administration of M1.Microscopic examination revealed a mild inflammatory response in the liver.Compared to intravenous injection,higher expression levels of adenoviral proteins were observed after retroperitoneal injection.Combined treatment with cyclosporine A resolved the liver and kidney dysfunction and increased the concentration of the adenovirus in the liver.The use of the novel oncolytic adenovirus mutant M1 in vivo is safe,and the combined administration of M1 with immunosuppressive agents was able to enhance the effectiveness and safety profile of M1.     

粒细胞巨噬细胞集落刺激因子与乙肝疫苗协同诱导小鼠细胞免疫应答

目的考察粒细胞巨噬细胞集落刺激因子(Gm-csf)对乙型肝炎疫苗免疫原性及诱导的细胞免疫效果的加强作用。方法将Gm-csf和乙型肝炎疫苗分别采用4种不同方式免疫BALB/c小鼠,免疫后,制备脾细胞,再以相应的HBsAg体外刺激,酶联免疫法(ELISA)测定细胞因子分泌水平,MTT法测定脾细胞对抗原刺激指数;以YAC-1细胞为靶细胞,测定细胞毒性T淋巴细胞活性;同时ELISA法测定血清中特异性抗体IgG1和IgG2a。结果GM+疫苗组小鼠脾细胞产生的IFN-γ水平最高,显著高于其它组(P<0.05),而各免疫组IL-5水平没有显著差别(P>0.05);GM+疫苗组小鼠脾细胞对抗原刺激的刺激指数显著高于其它各组(P<0.05);GM+疫苗组小鼠脾细胞对YCA-1的杀伤性显著高于其它各组(P<0.01)。结论通过Gm-csf的联合免疫,可提高乙型肝炎疫苗的免疫原性,增强乙型肝炎疫苗诱导的细胞免疫水平。     

Cell biology and immunology of malaria

Malaria is a vector-borne infectious disease caused by unicellular parasites of the genus Plasmodium. These obligate intracellular parasites have the unique capacity to infect and replicate within erythrocytes, which are terminally differentiated host cells that lack antigen presentation pathways. Prior to the cyclic erythrocytic infections that cause the characteristic clinical symptoms of malaria, the parasite undergoes an essential and clinically silent expansion phase in the liver. By infecting privileged host cells, employing programs of complex life stage conversions and expressing varying immunodominant antigens, Plasmodium parasites have evolved mechanisms to downmodulate protective immune responses against ongoing and even future infections. Consequently, anti-malaria immunity develops only gradually over many years of repeated and multiple infections in endemic areas. The identification of immune correlates of protection among the abundant non-protective host responses remains a research priority. Understanding the molecular and immunological mechanisms of the crosstalk between the parasite and the host is a prerequisite for the rational discovery and development of a safe, affordable, and protective anti-malaria vaccine.     

Innate immunity in allergic disease

The innate immune system consists of multiple cell types that express germline-encoded pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Allergens are frequently found in forms and mixtures that contain PAMPs and DAMPs. The innate immune system is interposed between the external environment and the internal acquired immune system. It is also an integral part of the airways, gut, and skin. These tissues face continuous exposure to allergens, PAMPs, and DAMPs. Interaction of allergens with the innate immune system normally results in immune tolerance but, in the case of allergic disease, this interaction induces recurring and/or chronic inflammation as well as the loss of immunologic tolerance. Upon activation by allergens, the innate immune response commits the acquired immune response to a variety of outcomes mediated by distinct T-cell subsets, such as T-helper 2, regulatory T, or T-helper 17 cells. New studies highlighted in this review underscore the close relationship between allergens, the innate immune system, and the acquired immune system that promotes homeostasis versus allergic disease.