Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T cells

Trafficking of transmembrane receptors to a specific intracellular compartment is conducted by adaptor molecules that bind to target motifs within the cytoplasmic domains of cargo proteins. We generated mice containing a lymphoid-specific deficiency of AP-1 using RNAi knockdown technology. Inhibition of AP-1 expression in thymocytes blocks progression from double-positive immature thymocytes, resulting in complete absence of CD4⁺ single-positive thymocytes and severe reduction of CD3⁺CD8⁺ single-positive thymocytes. Analysis of the contribution of AP-1 deficiency on the interaction between mature CD4⁺ T cells and antigen-presenting cells revealed that AP-1 is essential to efficient immune synapse formation and associated T cell activation, suggesting a possible mechanism of AP-1 function in thymocyte development.     

移植免疫耐受形成机理的思考

免疫耐受并非是器官移植领域特有的的现象,而是免疫学领域的普遍现象。本文强调“大量的移植抗原能够诱导宿主免疫系统特异性的免疫细胞凋亡以及造成细胞因子、抗体等免疫物质耗竭”是免疫耐受形成的一个重要原因,以此对许多免疫耐受现象进行解释,并从这个角度推断“在器官移植前后通过大量抗原诱导同种、异种器官移植形成免疫耐受”。     

女性下生殖道HPV感染和HPV相关的宫颈肿瘤

子宫颈病变是女性最常见的疾患之一.在女性癌瘤中,宫颈癌的发病率仅次于乳腺癌.人乳头状瘤病毒(HPV)感染在宫颈肿瘤的发病机制中起着重要的作用,许多学者关注HPV疫苗的预防和治疗.在女性生殖道HPV传播及继发性感染是局部性的,因此,针对这种局部性传播疫苗的有效性最好能用局部免疫的参数来评价.     

Humanized mouse as an appropriate model for accelerated global HIV research and vaccine development: current trend

Humanized mouse models currently have seen improved development and have received wide applications. Its usefulness is observed in cell and tissue transplant involving basic and applied human disease research. In this article, the development of a new generation of humanized mice was discussed as well as their relevant application in HIV disease. Furthermore, current techniques employed to overcome the initial limitations of mouse model were reviewed. Highly immunodeficient mice which support cell and tissue differentiation and do not reject xenografts are indispensable for generating additional appropriate models useful in disease study, this phenomenom deserves emphases, scientific highlight and a definitive research focus. Since the early 2000s, a series of immunodeficient mice appropriate for generating humanized mice has been successively developed by introducing the IL-2Rγ^null gene (e.g. NOD/SCID/γc^null and Rag2^nullγc^null mice) through various genomic approaches. These mice were generated by genetically introducing human cytokine genes into NOD/SCID/γc^null and Rag2^nullγc^null mouse backgrounds. The application of these techniques serves as a quick and appropriate mechanistic model for basic and therapeutic investigations of known and emerging infections.     

河南省部分地区健康人群流行性乙型脑炎病毒中和抗体监测

目的 分析健康人群流行性乙型脑炎（乙脑）病毒中和抗体水平特征和影响因素.方法 采用随机抽样方法在信阳市和洛阳市选择＜1岁、1～2岁、3～4岁、5～6岁、7～14岁、15～19岁、20 ～59岁、≥60岁8个年龄组健康人群,分别于2010年5月和11月两次采集血液标本并进行流行病学调查,用微量细胞中和试验检测乙脑病毒中和抗体.结果 两市共调查519人,两次共采集和检测有效血液标本1008份,其中男性乙脑病毒中和抗体阳性率为59.52％,女性为67.39％,男女中和抗体阳性率差异无统计学意义（x2=3.41,P＞0.05）.5月,两市中和抗体阳性率为58.66％,11月为61.20％,乙脑流行前后中和抗体阳性率差异无统计学意义（x2 =0.68,P＞0.05）.信阳市0～14岁中和抗体阳性率为55.19％,洛阳市为45.03％,两市0～14岁中和抗体阳性率差异无统计学意义（x2=3.53,P＞0.05）;信阳市≥15岁中和抗体阳性率为97.78％,洛阳市为48.94％,两市≥15岁中和抗体阳性率差异有统计学意义（x2=55.42,P＜0.05）.两市有乙脑免疫史者中和抗体阳性率为56.85％,无乙脑免疫史者为38.35％,有无免疫史者中和抗体阳性率差异有统计学意义（x2=10.88,P ＜0.05）.结论 信阳市和洛阳市≥15岁人群间、有无乙脑免疫史人群间乙脑病毒中和抗体均有显著性差异,建议信阳市和洛阳市加强0～14岁人群免疫接种,同时关注和探讨洛阳市≥15岁人群免疫策略.     

谷氨酰胺对老年胃肠道肿瘤患者术后蛋白质代谢及免疫功能的作用

目的:探讨谷氨酰胺对老年胃肠道肿瘤患者术后蛋白质代谢及免疫功能的影响。方法:选取2007-03/2010-03胃肠道肿瘤患者87例,术后2 h开始给予肠外营养,同时加入谷氨酰胺0.6 g/(Kg.d),持续8 d。采用单向免疫扩散法测定血清IgA、IgG、IgM,采用免疫组化法测定外周血CD3+、CD4+、CD8+、CD4+/CD8+,同时测定蛋白质代谢的指标(包括氮平衡、血浆白蛋白、前白蛋白、转铁蛋白)。结果:老年胃肠道肿瘤经治疗后CD3+、CD4+、CD8+、CD4+/CD8+、IgG、IgA、IgM显著升高,与治疗前比较差异有统计学意义(P<0.05);术后第4天Alb、PAB、TF显著下降(P<0.05),术后第8天得到较为明显的恢复(P<0.05);肿瘤患者负氮平衡状态术后早期加重,经谷氨酰胺治疗8 d后恢复至术前水平(P<0.05),差异有统计学意义。结论:谷氨酰胺可显著改善老年胃肠道肿瘤患者术后营养,提高患者的免疫功能。     

强效佐剂研究进展

许多佐剂具有炎症特性,缺乏特异性,并且具有毒性,因而其应用受到了限制.近年来,随着免疫学的发展,出现了大量潜在的新型佐剂,它们能以更加可控和特异的方式调节免疫应答,这将对现行及今后的疫苗策略产生重要影响.此文对于能靶向细胞、受体或信号通路等特定免疫组分的候选佐剂做一综述.     

DNA疫苗:从动物疫苗到人用疫苗的跨越

自从十多年前发现DNA可以作为疫苗诱导机体产生免疫应答以来,DNA疫苗研究已取得突破性进展.目前已有4种动物DNA疫苗获准上市.然而,在临床试验中,单纯的DNA疫苗免疫原性很弱.随着DNA疫苗设计策略和接种方式的改进,可以预期将会有更多的人用DNA疫苗逐步进入临床,并最终实现DNA疫苗从动物疫苗到人用疫苗的跨越.