γδT细胞在病毒免疫中的作用

γδT细胞被视为天然免疫和获得性免疫之间的桥梁,与NK细胞、巨噬细胞及树突状细胞等免疫细胞共同构成机体抵抗病原微生物的第一道防线.γδT细胞可以通过释放如穿孔素、颗粒酶等细胞毒性分子,表达Fas-FasL诱导细胞凋亡以及分泌IFN-γ等方式发挥细胞免疫效应,也可以释放IL-2、IL-4、IL-5、IL-7、IL-22等细胞因子调节体液免疫.γδT细胞在抗感染、抗肿瘤及免疫耐受等病理生理中发挥着重要作用.本文就γδT细胞及其主要功能在抗病毒免疫中所扮演的作用作一综述.     

Targets of immunotherapy for hepatocellular carcinoma: An update

Hepatocellular carcinoma, the most common primary liver cancer, in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages. Although, surgical resection, ablation, liver transplant, and locoregional therapies are available for early stages; however, there are yet no effective treatment for advanced and recurrent tumors. Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression. However, still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment. At present, the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy, immune checkpoint therapy, adoptive cell transfer therapy, and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells. This review discusses the recent key development, the basis of drug resistance, immune evasion, immune tolerance, the available therapies based on stage of the tumor, and the ongoing clinical trials on immune checkpoint inhibitor therapy, adoptive cell transfer therapy, oncolytic viral vaccine therapy, and combination therapy.     

Induction of protective immunity against H1N1 influenza A(H1N1)pdm09 with spray-dried and electron-beam sterilised vaccines in non-human primates

Currently, the need for cooled storage and the impossibility of terminal sterilisation are major drawbacks in vaccine manufacturing and distribution. To overcome current restrictions a preclinical safety and efficacy study was conducted to evaluate new influenza A vaccine formulations regarding thermal resistance, resistance against irradiation-mediated damage and storage stability. We evaluated the efficacy of novel antigen stabilizing and protecting solutions (SPS) to protect influenza A(H1N1)pdm09 split virus antigen under experimental conditions in vitro and in vivo.     

The virus-induced HSPs regulate the apoptosis of operatus APCs that results in autoimmunity,not in homeostasis

The viruses are salient in the roles of environmental factors that trigger autoimmunity. The virus realizes its effects by the power of its induction of heat shock proteins (HSPs) as well as by the viral IE-axis-mediated conversion of organ epithelial cells into virgin de novo professional antigen-presenting cells (APCs). The HSP is the accomplished operator in homeostasis by the logic of it being the regulator of apoptosis. That HSP which regulates and controls different points in the pathways of apoptosis is rationally propitious as both HSP and apoptosis are highly conserved in multicellular organisms. By virtue of its regulation of apoptosis, the HSP is also involved in human autoimmunity and this involvement is tripartite: (i) adornment of viral IE-axis-generated virgin de novo professional APCs with HSP-induced co-stimulatory molecules which transform these otherwise epithelial cells to achieve the status of fledged competent antigen-presenters, the operatus APCs, which are liable to apoptosis that becomes the initiator of organ damages that can culminate in the autoimmune syndrome(s); apoptosis is a routine fate that befalls all APCs following their antigen presentation; (ii) molecular mimicry mechanism: epitopes on the HSP may be mistaken for viral peptides and be presented by operatus APCs to autoreactive TCRs resulting in the apoptosis of the operatus APCs; and (iii) regulation of MHC class II-DR-mediated apoptosis of operatus APCs which can ultimately consequent in organ-specific autoimmune syndromes. We should remember, however, that Nature's intended purpose for the apoptosis of the professional APCs is benevolence: as a principal regulator of homeostasis. It is only from the apoptosis of our postulated operatus APCs that the apoptotic consequence can be deleterious, an autoimmune syndrome(s). The transformation of virgin de novo professional APCs to operatus APCs mirrors the maturation of DCs, through their acquisition of HSP-induced co-stimulatory molecules; and what happens to mature DCs as antigen-presenters that ends in homeostasis is replicated by what happens to operatus APCs that ends instead in autoimmune syndromes (Fig. 1).     

多种病毒集合检测芯片的研制及其在临床血清标本检测中的初步应用

目的 研制黄热病、西尼罗热、登革热、基孔肯雅热、埃博拉出血热、马尔堡出血热、拉沙热等多种病毒性传染病集合检测基因芯片,并建立一种适用于直接检测核酸含量较低临床血清标本的新型芯片靶基因扩增标记方法.方法 设计并筛选出上述病毒70mer寡核苷酸特异探针各20条,打印于同一基因芯片上；以phi29 DNA聚合酶结合带标签序列的随机引物进行临床标本中病毒全基因组扩增,再以Cy3荧光染料标记的标签序列引物进行PCR随机扩增标记,标记产物用多种病毒芯片进行杂交检测.结果 检测1～4型登革热、基孔肯雅热病例临床血清标本,结果显示该方法准确、特异、敏感；检测西尼罗热、黄热病、埃博拉出血热、马尔堡出血热、拉沙热等病毒核酸的模拟血清标本,同样得到特异的阳性杂交信号,与预期结果一致.结论 本研究建立的多种病毒集合检测基因芯片及其靶基因扩增标记方法,可直接应用于血清标本中上述病毒核酸的检测.     

Growth factor receptor expression in anal squamous lesions: modifications associated with oncogenic human papillomavirus and human immunodeficiency virus

High prevalence of squamous anal lesions is linked to oncogenic human papillomavirus (HPV). Human immunodeficiency virus (HIV) promotes anal carcinogenesis. Epidermal growth factor receptor (EGFR), HER2/neu, c-Met, and vascular endothelial growth factor receptor-1 (VEGFR1) (tyrosine kinase growth factor receptors) are implicated in tumor progression, but little is known about their role in anal lesions. We investigated their expression and distribution in normal, dysplastic, and carcinomatous anal epithelium and then tried to analyze the effects on these variables of HPV and the HIV-positive status. Seventy-one HIV-positive and 47 HIV-negative patients were selected. We studied growth factor receptors, p16 and Ki67 expression, by in situ hybridization, fluorescent in situ hybridization (FISH) and chromogen in situ hybridization (CISH), immunocytochemistry, and morphological quantification in 226 lesions, either infected by HPV6 and 11 (31 condylomas acuminata) or infected with oncogenic HPVs (48 invasive cancers, 147 anal intraepithelial neoplasias). No HER2/neu was detected. Strong EGFR immunolabeling was not accompanied by gene amplification. The number and intensity of EGFR- and c-Met–immunoreactive cells increased significantly during lesion progression, highlighting the effects of oncogenic HPVs. EGFR, c-Met, VEGFR1, and p16 were coexpressed in 96% of invasive cancers. HIV-modified c-Met expression in condyloma acuminata (P < .008) and invasive cancers (P < .02). Strong HIV-related immunodeficiency and an absence of antiretroviral therapy increased c-Met and/or EGFR expression. HIV-positive anal cancers showed correlated c-Met and VEGFR1 (P < .003), strong p16 labeling, and an increased Ki67 proliferation. The finding that EGFR, c-Met, and VEGFR1 involved in carcinogenesis are well-represented and coexpressed in anal cancers, especially in HIV-positive population, suggests possible novel targeted treatments for anal diseases.     

菊花总黄酮对转染RSV的A549细胞RANTES及MCP-1表达的影响

【目的】探讨菊花总黄酮对呼吸道合胞病毒(Respiratory Syncytial Virus,RSV)转染 A549细胞诱导激活正常 T 细胞表达和分泌因子(regulated upon activation ,normal Tcell expressed and secreted ,RANTES)及单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)释放作用影响。【方法】实验分为正常对照组,病毒对照组,菊花总黄酮组和巴韦林组。在人喉癌上皮细胞(Hep-2细胞)和气道上皮细胞(A549)分别加入菊花总黄酮和巴韦林的含药维持液,测定上述两种药物的最大无毒浓度；RSV 转染 Hep-2细胞,观察药物对 RSV 的病毒抑制作用；RSV 转染 A549细胞,ELISA 法测细胞趋化因子 RANTES 及 MCP-1含量。【结果】菊花总黄酮组50%有效率优于巴韦林组,差异有统计学意义(P <0.05)；菊花总黄酮组 RANTES、MCP-1明显降低,但高于正常细胞组,优于巴韦林组,差异有统计学意义(P <0.05)。【结论】菊花总黄酮能够抑制 RSV 活性,明显降低 A549细胞释放 RANTES、MCP-1,缓解患儿的呼吸道症状。     

置IUD子宫异常出血者子宫内膜细菌和病毒感染的研究

本文研究了育龄妇女子宫内膜细菌及病毒感染与宫内节育器（ＩＵＤ）所致子宫异常出血的关系。结果表明。置ＩＵＤ有异常出血组细菌总感染率为１０．５％（厌氧菌感染８．８％，需氧菌感染１．７％），显著高于未置ＩＵＤ正常组，是置ＩＵＤ未出血组的３．６２倍。置ＩＵＤ有异常出血组病毒总感染率为２９．５％。（巨细胞病毒（ＣＭＶ）感染１２．５％，单纯疱疹病毒Ⅱ（ＨＳＶⅡ）感染１７％，显著高于置ＩＵＤ无异常出血组和未置ＩＵＤ正常组。置ＩＵＤ＜１２月有异常出血者的细菌感染率显著高于置ＩＵＤ＞１２月者；而病毒感染则反之。宫颈糜烂的程度与置ＩＵＤ子宫有异常出血者宫内感染有关。     

Acute deteriorations in neonatal chronic lung disease

Preterm infants with chronic lung disease (CLD) have frequent respiratory relapses. The aim of this study was to assess the aetiology of such deteriorations and in particular the proportion due to viral infections. During the study period 118 preterm infants with birth weight <1500g were consecutively admitted to the neonatal intensive care unit; 22 (18.6%) developed CLD. At the onset of all respiratory deteriorations, infants were examined for the presence of patent ductus arteriosus, apnoea or aspiration; they were also carefully screened for both viral and bacterial infection. The 22 infants had a total of 74 episodes of respiratory deterioration; median 3 per baby (range 1–8). Two episodes were associated with patent ductus arteriosus, 18 with apnoea and 5 with aspiration. Infection was suspected or proven in association with all other episodes. On ten occasions the infants had positive blood cultures and on a further eight, bacteria were isolated only from the endotracheal or nasopharyngeal secretions. On the remaining 31 occasions, 27 associated with chest X-ray film abnormalities, infection was suspected, but no bacteria isolated. Viral infections were identified in association with 8 (11%) of these episodes. We conclude viral infection should be considered as a cause of otherwise unexplained respiratory deteriorations in infants with neonatal CLD.