中国HIV感染长期不进展者相关免疫指标的研究

目的:研究中国HIV感染长期不进展者(Long-term nonprogressors,LTNP)相关免疫指标的变化。方法:采集284例未经抗HIV治疗的LTNP、典型进展的HIV感染者和AIDS病人及130例HIV抗体阴性健康人的抗凝全血,应用流式细胞仪分析技术对CD8+T淋巴细胞、NK细胞及DC细胞进行测定。结果:LTNPCD8+T淋巴细胞绝对值[(1104.51±511.81)个/μl]高于AIDS病人[(678.40±295.39)个/μl,P<0.05]。LTNPNK细胞的绝对值[(377.59±289.23)个/μl]显著高于HIV感染者[(292.49±445.87)个/μl]和AIDS病人[(153.62±110.36)个/μl,P<0.05]。LTNPCD123+DCs细胞绝对值[(6.76±3.74)个/μl]高于HIV感染者[(5.30±3.16)个/μl]和AIDS病人[(3.32±2.09)个/μl,P<0.05]。LTNPCD11c+DCs细胞绝对值[(21.73±11.92)个/μl]高于HIV感染者[(14.51±9.53)个/μl]和AIDS病人[(7.27±3.74)个/μl,P<0.05]。结论:LTNPCD8+T淋巴细胞、NK细胞和DC细胞高于典型进展的HIV感染者和AIDS病人,是延缓疾病进程的重要因素。     

Anaplasma phagocytophilum delay of neutrophil apoptosis through the p38 mitogen-activated protein kinase signal pathway

Human granulocytic anaplasmosis is caused by the obligate intracellular bacterium Anaplasma phagocytophilum. The bacterium avoids host innate defenses in part by infecting, surviving in, and propagating in neutrophils, as well as by inhibiting neutrophil apoptosis. However, the mechanisms of A. phagocytophilum survival in neutrophils and the inhibition of spontaneous apoptosis are not well understood. In this study, we demonstrated that antiapoptotic Mcl-1 protein (Bcl-2 family) expression is maintained and that inhibition of procaspase-3 processing occurs in A. phagocytophilum-infected human neutrophils. An evaluation of p38 mitogen-activated protein kinase (MAPK) showed evidence of increased phosphorylation with infection. Moreover, antagonism of p38 MAPK by the inhibitor SB203580 reversed apoptosis inhibition in live or heat-killed A. phagocytophilum-infected neutrophils. A role for the autocrine or paracrine production of antiapoptotic interleukin 8 (IL-8) expressed with A. phagocytophilum infection was excluded by the use of IL-8-, IL-8R1 (CXCR1)-, and IL-8R2 (CXCR2)-blocking antibodies. As previously demonstrated, the antiapoptotic effect was initially mediated by exposure to A. phagocytophilum components in heat-killed bacteria. However, an important role for active infection is demonstrated by the additional delay in apoptosis with intracellular growth and the refractory abrogation of this response by the p38 MAPK inhibitor 3 to 6 h after neutrophil infection. These results suggest that the initial activation of the p38 MAPK pathway leading to A. phagocytophilum-delayed neutrophil apoptosis is bypassed with active intracellular infection. Moreover, active intracellular infection contributes more to the overall delay in apoptosis than do components of heat-killed A. phagocytophilum alone.     

Graves病患者TRAb与抗TSHAb抗体关系的初步研究

根据自身免疫性甲状腺疾病发病机制的独特型－抗独特型免疫免疫学说，用兔抗人ＴＳＨＡｂ检测ＴＳＨ抗独特型抗体（ＴＳＨＡｂ２）。以正常人为对照，以其结合率＾－ｘ＋２ｓ为正常值上限，大于此值为阳性。６０例ＴＲＡｂ阳性病人，６５％病人ＴＳＨＡｂ２阳性，而４０例ＴＲＡｂ阳性病人中，只有５％病人ＴＳＨＡｂ２阳性。两组差异显著（Ｐ〈０．０５）。ＴＲＡｂ和ＴＳＨＡｂ２呈正相关（ｒ＝０．６４５，Ｐ〈０．０１）。同时用     

Pentoxifylline attenuates the development of hyperalgesia in a rat model of neuropathic pain

Pentoxifylline, a non-specific cytokine inhibitor, has shown to be beneficial in inflammatory pain in both experimental and clinical studies. The present study demonstrates for the first time, to our knowledge, the antihyperalgesic effect of pentoxifylline in the neuropathic pain using L5 spinal nerve transection rat model. In a preventive paradigm, pentoxifylline (12.5, 25, 50, or 100 mg/kg intraperitoneally) was administered systemically daily, beginning 1 h prior to nerve transection. Pentoxifylline (50, or 100 mg/kg i.p.) produced significant decrease in the mechanical and thermal hyperalgesia. However, pentoxifylline (100 mg/kg i.p.) did not influence the paw pressure thresholds and paw withdrawal latency in sham-operated rats. In order to understand the possible antinocicieptive effect of pentoxifylline in neuropathic pain, we examined the level of TNFα, IL-1β, IL-6 and IL-10 protein in the contralateral brain on day 7 post-transection. Pentoxifylline administration resulted in a dose-dependent reduction of the production of proinflammatory cytokines like TNFα, IL-1β and IL-6, and enhancement of IL-10. Furthermore, we investigated the activity of nuclear factor kappa B (NF-κB) in the contralateral brain on days 7 after surgery. In accordance with the change of proinflammatory cytokines, Pentoxifylline (50 or 100 mg/kg) significantly inhibited the activation of NF-κB in the brain. This research supports a growing body of literature emphasizing the importance of neuroinflammation and neuroimmune activation in the development of neuropathic pain states, and the potential preventive value of pentoxifylline in the treatment of neuropathic pain.     

王棕花粉过敏原基因的克隆表达、纯化及免疫学鉴定

目的 克隆并表达王棕花粉中泛变应原肌动蛋白抑制蛋白(profilin).方法 利用RT-PCR结合RACE技术克隆王棕花粉中泛变应原profilin的全长基因,并进行序列分析.然后设计带有酶切位点的特异性引物,采用RT-PCR获得整个王棕花粉profilin的开放阅读框,将其与pET28a载体连接并转化大肠杆菌BL21(DE3)进行诱导表达,通过Ni2+亲和层析柱对重组蛋白进行纯化,采用Western blot检测其IgE结合活性.结果 克隆获得了王棕花粉profilin的全长基因,由675个碱基组成,开放阅读框为396个碱基(包括终止密码子),编码131个氨基酸.经分析,这个序列编码的蛋白为小分子质量酸性蛋白,等电点为4.86,相对分子质量(Mr)约为14.2×103.此序列已被GenBank收录,登录号为EF173599.重组王棕花粉profilin在大肠杆菌中高效表达,进一步经Ni2+亲和层析柱纯化后经Western blot检测具有良好的免疫学活性.结论 成功克隆和表达了王棕花粉profilin,为王棕过敏的诊断和免疫治疗奠定了基础.