一种具有抗HIV和其它病毒作用的生物制剂CV-N

蓝藻菌病毒素-N（Cyanovirin-N,CV-N）是近年来在蓝藻菌中发现的一种新的具有抗HIV病毒活性的蛋白质,它可以和HIV病毒的外壳糖蛋白gp120和gp41发生特异性的结合作用,不可逆的使病毒失去感染细胞的能力.本文主要针对CV-N的生物学性质及其应用前景进行了介绍.     

香菇多糖抗诱变性研究

应用果蝇伴性隐性致死试验,以甲磺酸甲酯作为直接诱变剂,以环磷酰胺作为间接诱变剂对香菇多糖注射液抗诱变性进行测试,证实香菇多糖对甲磺酸甲酯的强诱变效应有非常显著的抑制作用,具有极明显的抗诱变性,而对环磷酰胺的诱变性抑制作用不明显。提示香菇多糖含有抗突变物质和具有抗突变作用,对预防人类癌有实用价值。     

检测HIV早期感染的血清学方法

艾滋病，即获得性免疫缺陷综合征（AIDS）是由人类免疫缺陷病毒（HIV）引起的一种免疫缺陷性疾病。世界范围内AIDS预防控制工作的首要任务在于识别出早期感染的人群（新发感染人群），进而估计HIV的发病率，掌握HIV感染的变化趋势，同时对早期感染人群进行干预和有效控制，以遏制HIV的蔓延趋势。     

HIV基因疫苗的研究进展

根据近来的报道，全世界有5000000人感染人类免疫缺陷病毒（HIV），3000000人死于艾滋病（获得性免疫缺陷综合征，AIDS）。HIV的广泛流行将给全人类的健康带来严重的危害。因此，研发一种安全而有效的HIV疫苗是预防艾滋病的有效且经济的方法。到目前为止，研究显示细胞介导的免疫反应可以有效的控制HIV复制并减慢AIDS病程，因此成为疫苗研究的主要方向。但是，以重组蛋白为主的传统疫苗不能够有效的诱发细胞介导的免疫反应，因此不能有效的控制HIV-1的复制和传播。近来，一种被称为基因疫苗（geneticvaccine）的新技术平台给艾滋病疫苗的研究带来新的希望。这种以包括DNA疫苗和重组病毒载体疫苗为主的基因疫苗可以将目的基因转入细胞内并表达为内源性蛋白，并凭借MHC Class I旁路提呈给免疫系统而诱发细胞介导的免疫反应。因此以基因疫苗为主的技术策略正被广泛应用于抗HIV疫苗的研究。     

女贞子多糖免疫增强作用的体外实验研究

应用３Ｈ－ＴｄＲ掺入法检测女贞子多糖（ＬＬＳ）体外对小鼠免疫细胞增殖的影响。实验结果显示：１５６￣１２５０ｕｇ／ｍｌ的女贞子多糖对正常小鼠脾淋巴细胞、Ｂａｌｂ／ｃ裸鼠脾淋巴细胞（Ｂ细胞）及通过尼龙毛柱的脾细胞（Ｔ细胞）均有直接的刺激增殖作用，量效关系明显；巨噬细胞在脾淋巴细胞增殖反应中起一定的辅助作用。     

HIV辅受体的研究进展

目前关于HIV辅助受体折研究已经成为一个研究热点，HIV辅助受体的发现以及HIV与辅助受体之间作用机制的深入研究。为防止HIV感染、治疗艾滋病提供了新的思路。本文旨在阐述目前HIV辅受体的研究进展。     

香菇多糖对小鼠胸腺,脾脏的免疫电镜观察

香菇多糖对小鼠胸腺、脾脏的免疫电镜观察兰州医学院（７３００００）白润江，于红娟，任娅，马端，王嘉军中药的免疫机理研究近年来倍受重视，我们的实验曾表明：香菇多糖有促进非特异免疫的功能，促进细胞免疫，促进抗体形成和抑制肿瘤生长的作用。本文在此基础上同时用...     

HIV外膜蛋白的结构与功能研究进展

人免疫缺陷病毒 (ｈｕｍａｎｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙｖｉｒｕｓ ,ＨＩＶ)ｅｎｖ基因编码的前体分子 ｇｐ16 0 (ＨＩＶ 1)或ｇｐ140 (ＨＩＶ 2 )经蛋白酶剪切加工后 ,成为成熟的外膜蛋白ｇｐ12 0 (ＨＩＶ 1) ｇｐ10 5 (ＨＩＶ 2 )和跨膜蛋白 ｇｐ41(ＨＩＶ 1) ｇｐ36 (ＨＩＶ 2 )。在病毒表面 ,外膜蛋白和跨膜蛋白以非共价键结合成Ｅｎｖ异二聚体 ,3个异二聚体组成包膜超分子结构 ,形成病毒表面的突起[1 ] 。ＨＩＶ外膜蛋白是激发体液免疫和细胞免疫应答的最重要蛋白抗原。自从 1984年Ｋｌａｔｚｍａｎｎ等发现ＨＩＶ与ＣＤ4+细…     

四种HIV抗体确证试剂盒用于HIV感染检测性能的比较研究

目的:比较4种HIV抗体确证试剂盒的检测性能,为临床使用试剂提供参考。方法:使用2种免疫印迹法(Western blot, WB)试剂、2种重组/线性免疫印迹法(recombinant immunoblot assay/line immune assay,RIBA/LIA)试剂平行检测185份样本,采用McNermar...     

血液透析患者感染HIV、TP、HBV和HCV的情况调查

目的：了解血液透析患者人类免疫缺陷病毒（HIV）、梅毒螺旋体（TP）、乙肝病毒（HBV）、丙肝病毒（HCV）感染现状,为控制传染科疾病的医源性感染提供依据。方法：对进行血液透析治疗的320例患者进行HIV、TP、乙肝五项、抗-HCV检测。结果：本文患者HIV感染0例,梅毒感染7例（占2.19%）,乙肝感染153例（占47.81%）,与国内相关报道大致相符,丙肝感染37例（占11.56%）,低于国内相关统计数据;其中梅毒＋丙肝混合感染1例,梅毒＋乙肝混合感染4例,丙肝＋乙肝混合感染20例,总感染率达到53.75%。严格感控措施后,感染率由44.44%降到了21.21%。结论：血液透析患者是经血传播疾病的高发人群,与正常健康查体人群的梅毒、乙肝、丙肝的感染率有较大差异,混合感染多见,严格感控措施后感染率下降明显,提示加强血液透析患者传染性疾病的监控,有助于阻止医源性传染性疾病的传播。     

Clinical implications of discordant viral and immune outcomes following protease inhibitor containing antiretroviral therapy for HIV-infected children

Many HIV-infected children treated with protease inhibitors (PI) reconstitute immunity despite viral breakthrough predicting disease progression. We studied a unique cohort of PI treated children with advanced disease who demonstrated sustained CD4 T cell counts but median post therapy viral load rebounded to >4.0 log₁₀ copies/ml. Phylogenetic relationships between pre- and post-therapy viruses reveals significant bottlenecks for quasispecies with natural polymorphisms mapping outside of protease active site providing selective advantage for emergence. Among discordant subjects post-therapy viruses fell into two phenotypes; high viral loads (median >5.0 log₁₀ copies/ml) and attenuated post-therapy replication (median <4.0 log₁₀ copies/ml). Both groups showed similar degrees of CD4 T cell immune reconstitution and were similar to children who optimally suppressed virus to <400 copies/ml. Both high fit and low fit discordant response groups showed high reconstitution of naïve CD4 CD45RA T cells (median 388 and 357 cells/μl, respectively). Naïve T cells increases suggest virus replicating under PI selective pressure do not impair thymic output. If therapeutic options are limited, selection of therapy which allows immune reconstitution despite suboptimal viral control may be beneficial. This novel paradigm for virus/host interactions may lead to therapeutic approaches to attenuate viral pathogenesis.     

甲胎蛋白对树突状细胞免疫表型影响的体外研究

目的：研究甲胎蛋白（Alpha Fetoprotein,AFP)对树突状细胞（DendriticCell,DC)免疫表型的影响。方法：用流式细胞仪分析体外培养扩增的小鼠骨髓DC表面H-2K^b、I-A^b、B-7-1和B7-2等免疫分子的表达。结果：与对照组相比,AFP可明显上调DC的B7-1和B7-2分子水平、下调H-2K^b和I-A^b的表达、但抑制I-A^b的程度较轻;AFP抗原抗体复合物极度抑制H-2K^b分子表达、对I-A^b的下调程度高于AFP组,而对B7-1和B7-2分子几乎无影响：AFP抗体和人血清白蛋白（HSA）对DC免疫分子活性的影响均较弱,结论：AFP可作为肝癌相关抗原,致敏DC,部分上调DC免疫活性分子的表达。     

Tripterygium wilfordii Hook F extract in cART-treated HIV patients with poor immune response: a pilot study to assess its immunomodulatory effects and safety

Background:

Despite combination antiretroviral therapy (cART), 20% of HIV-infected patients are unable to achieve adequate immunologic recovery, in which immune activation plays a crucial role. We hypothesize that extract of Tripterygium wilfordii Hook F (TwHF), a Chinese medication used to treat autoimmune diseases, has immunomodulatory effects that may help CD4 cell recovery.

Methods:

Eighteen cART-treated HIV-infected patients virally suppressed for over 12 months with suboptimal CD4 cell recovery were enrolled. TwHF extract was administered at a dosage of 10?mg three times daily for 12 months. T-cell subsets and activation markers were evaluated at baseline and during follow-up. The trial was registered at Clinicaltrials.gov (NCT02002286).

Results:

TwHF extract was associated with a mean increase in CD4 cell count of 88?cells/μl (95% confidential interval [CI], 72–105?cells/μl) after one year of treatment. A significant increase in the mean rate of CD4 cell recovery (26 before vs 75?cells/μl/year after TwHF use, P?Conclusion:

Use of TwHF extract in HIV-infected patients was associated with a reduction in T-cell activation and improved CD4 recovery with an excellent safety profile.     

The immunopathogenesis of the HIV tuberculosis immune reconstitution inflammatory syndrome

HIV‐1 patients co‐infected with some pathogens are at risk of developing the immune reconstitution inflammatory syndrome (IRIS) when initiating antiretroviral therapy (ART). IRIS is characterized by inflammation leading to the clinical worsening of a treated infection or the unmasking of a previously undiagnosed condition or infection. It is commonly associated with tuberculosis (TB), 8–43% of the HIV‐TB co‐infected patients prescribed with antitubercular treatment and ART develop TB‐IRIS. Although IRIS has been recognized for over 20 years, relatively little was known until recently about its pathogenesis. Despite these advances in understanding IRIS, there remains no immune biomarker for diagnostic or prognostic purposes. Here, we review the risk factors associated with TB‐IRIS, the challenges in studying this syndrome, and how T lymphocytes, dysregulated cytokine responses, and innate immunity may contribute to the development of TB‐IRIS.     

Excess apoptosis of mononuclear cells contributes to the depressed cytomegalovirus-specific immunity in HIV-infected patients on HAART

HIV-infected patients on highly active antiretroviral therapy (HAART) have persistently decreased cytomegalovirus (CMV)-specific proliferative responses [lymphocyte proliferation assay (LPA)] in spite of increases in CD4+ T cell counts. Here we demonstrate an association between apoptosis of unstimulated peripheral blood mononuclear cells (uPBMC) and decreased CMV-LPA. HAART recipients had more apoptosis of uPBMC than controls when measured by caspases 3, 8, and 9 activities and by annexin V binding. Patients with undetectable HIV replication maintained significantly higher apoptosis of CD4+ and CD14+ cells compared to controls. CMV-LPA decreased with higher apoptosis of uPBMC in patients only. This association was independent of CD4+ cell counts or HIV replication. Furthermore, rescuing PBMC from apoptosis with crmA, but not with TRAIL- or Fas-pathway blocking agents or with other caspase inhibitors, increased CMV-LPA in HAART recipients. This effect was not observed in uninfected controls, further indicating that the down regulatory effect of apoptosis on cell-mediated immunity (CMI) was specifically associated with the HIV-infected status.     

Circulating immune complexes in HIV-infected persons

Summary Circulating immune complexes are part of normal immune defense mechanisms and, therefore, present in various infectious — bacterial and viral — diseases. On the other hand, they are obviously involved in pathogenic mechanisms, e.g., autoimmune diseases or different forms of malignancies. Both autoimmune and infectious features are recorded in the acquired immunodeficiency syndrome. Thus, elevated levels of antigen-antibody complexes in HIV-infected persons had to be expected, and they were in fact demonstrated by several authors. In a cohort study, it was additionally shown that circulating immune complexes are of prognostic relevance. After an introduction concerning the physiological and pathophysiological role of circulating immune complexes in general, their involvement in the course of HIV infections is presented and discussed. In addition, there is a critical review of the most commonly applied assay systems for the detection and quantification of circulating immune complexes.Abbreviations AIDS Acquired immunodeficiency syndrome - CIC Circulating immune complexes - HIV Human immunedeficiency virus - BGA Bundesgesundheitsamt - PEG Polyethylene glycol Supported by DFG, grant 797/1-1     

Challenges in diagnosis and management of Cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settings

In many resource-limited settings, cryptococcal meningitis (CM) contributes up to 20% of all deaths with further complications due to Immune Reconstitution Inflammatory Syndrome (IRIS). We present a case report on a patient who developed CM-IRIS and then subsequent CM-relapse with a fluconazole-resistant organism and then later CM-IRIS once again, manifesting as cystic cryptococcomas, hydrocephalus, and sterile CSF. In this case we, demonstrate that CM-IRIS and persistent low level cryptococcal infection are not mutually exclusive phenomena. The management of IRIS with corticosteroids may increase the risk of culture positive CM-relapse which may further increase the risk of recurrent IRIS and resulting complications including death. We also highlight the role of imaging and fluconazole resistance testing in patients with recurrent meningitis and the importance of CSF cultures in guiding treatment decisions.     

门静脉注射供体脾细胞联合应用环孢素A诱导免疫耐受的实验研究

目的:利用大鼠异位心脏移植模型,行移植时经门静脉注射供体脾细胞联合应用环孢素A(CsA)诱导免疫耐受的实验研究,并从细胞免疫角度探讨其诱导免疫耐受机制。方法:受体鼠移植术前经门静脉注射供体脾细胞联合短期应用环孢素A(CsA)。采用MTT法检测术后受体鼠脾淋巴细胞IL-2产生水平及NK细胞活性,采用ELISA检测受体鼠IFN-γ表达水平。结果:门静脉注射供体脾细胞联合应用CsA能显著延长大鼠心脏移植物的存活期,且明显抑制受体脾淋巴细胞IL-2,IFN-γ的表达及NK细胞活性。结论:门静脉注射供体脾细胞能有效地诱导免疫耐受,干扰IL-2-NK-IFN-γ免疫网络功能可能是门静脉注射供体脾细胞诱导免疫耐受的机制之一。     

Regulatory T cells generated during cytomegalovirus in vitro stimulation of mononuclear cells from HIV-infected individuals on HAART correlate with decreased lymphocyte proliferation

HIV-infected patients fail to fully recover cell-mediated immunity despite HAART. To identify regulatory factors, we studied the phenotype and function of in vitro cytomegalovirus (CMV)-stimulated T cells from HAART recipients. CFSE-measured proliferation showed CD4⁺ and CD8⁺ cells dividing in CMV-stimulated cultures. Compared with healthy controls, CMV-stimulated lymphocytes from HAART recipients had lower ³H-thymidine incorporation; lower IFNγ and TNFα production; higher CD4⁺CD27⁻CD28⁻ and CD8⁺CD27⁻CD28⁻ frequencies; lower CD4⁺CD25^hi; and higher FoxP3 expression in CD8⁺CD25^hi cells. CMV-specific proliferation correlated with higher IFNγ, TNFα and IL10 levels and higher CD4⁺perforin⁺ and CD8⁺perforin⁺ frequencies. Decreased proliferation correlated with higher CD4⁺CD27⁻CD28⁻ frequencies and TGFβ1 production, which also correlated with each other. Anti-TGFβ1 neutralizing antibodies restored CMV-specific proliferation in a dose-dependent fashion. In HIV-infected subjects, decreased proliferation correlated with higher CMV-stimulated CD8⁺CD25^hi frequencies and their FoxP3 expression. These data indicate that FoxP3- and TGFβ1-expressing regulatory T cells contribute to decreased immunity in HAART recipients.     

可调控表达IL-2基因骨髓基质细胞促进异基因骨髓移植小鼠免疫功能重建

目的　探讨可调控表达IL 2基因的骨髓基质细胞系对异基因骨髓移植小鼠免疫功能重建的促进作用。方法　构建四环素诱导的表达小鼠IL 2基因的逆转录病毒载体 ,转染包装细胞PT6 7,感染骨髓基质细胞系QXMSC1(H 2 d) ,构建可诱导表达IL 2基因的工程化骨髓基质细胞系QXM SC1tet on IL 2。受体小鼠C5 7BL 6 (H 2 b)经γ射线致死剂量照射后 ,输入供体BALB c(H 2 d)骨髓细胞1× 10 7 只 (去除T细胞 ) ,同时输注骨髓基质细胞QXMSC1tet on IL 2 5× 10 5 只。灌服多西环素 (Dox)诱导IL 2表达。于骨髓移植 (BMT)后 30d、6 0d检测小鼠脾细胞对ConA的反应强度 ,空斑形成细胞(PFC)数和迟发型超敏反应 (DTH) ,脾细胞中T辅助细胞前体频数 (HTLp)及移植后小鼠脾脏T细胞亚群CD4 + CD8+ 的比值 ,评价BMT后免疫功能的恢复情况。结果　成功建立四环素诱导IL 2基因表达的基因工程化骨髓基质细胞系QXMSC1tet on IL 2。异基因BMT、联合输注QXMSC1tet on IL 2能显著提高BMT小鼠脾细胞对ConA的反应 ,增加脾脏淋巴细胞HTLp及PFC数目 ,并使DTH反应增强 ,改善小鼠脾脏T细胞亚群CD4 + CD8+ 的比值。结论　共输注可调控表达IL 2基因的骨髓基质细胞可促进异基因移植小鼠免疫功能重建。