DNA vaccine therapy for chronic hepatitis C virus (HCV) infection: immune control of a moving target

The use of DNA plasmids for DNA vaccination was first described in the early 1990s. DNA vaccinations were successful in small animal models but in larger animals and humans problems appeared. One major obstacle, effective delivery, has been partly overcome by new delivery techniques, such as transdermal delivery with the gene gun, and in vivo electroporation. We are entering a new era of DNA vaccination, where such techniques can be tested in humans. DNA vaccination may be a useful therapy for chronic hepatitis C virus (HCV) infections. Patients with these infections have a reduced T cell response to the invading virus. The genetic variability of HCV, its immunomodulatory properties and high replication rate contribute to chronicity. By providing the correct stimulus T cells may be activated to clear the infection. The vaccination is intended to induce a coordinated immune-based attack on the continuously moving HCV target. If effective, this should help in clearing the infection.     

The role of cathelicidin and defensins in pulmonary inflammatory diseases

Antimicrobial peptides (AMPs) protect the epithelia of mucosal organs like the respiratory or the gastrointestinal tract from invading microorganisms. As an integral part of the innate immune system they display antimicrobial activity against Gram- and Gram-negative bacteria as well as against fungi and enveloped and non-enveloped viruses. Besides their microbicidal effects they have important functions in the regulation of repair and inflammation. AMPs are sometimes referred to as ‘alarmins’ due to their ability to recruit, modulate and activate components of the immune system. In contrast, some AMPs suppress activation of the immune system. AMPs are also involved in tissue repair, cancer biology and angiogenesis. Based on their antimicrobial and immunomodulatoy functions, AMPs are probably involved in the pathogenesis of infectious and inflammatory diseases of the lung. Inborn or acquired deficiencies contribute to susceptibility to infection and colonisation. The potential pro-inflammatory role of AMPs contributes to the disease processes in inflammatory disorders such as asthma, chronic obstructive pulmonary disease, sepsis or pulmonary fibrosis. This review summarises the knowledge about the functions of AMPs in the pulmonary innate host defence system and their role in respiratory disease.     

Invasive fungal infections in the pediatric population

Alzheimer’s disease is a leading cause of dementia with a multifactorial and still barely understood etiology. A growing body of epidemiologic and experimental data support a role for infectious agents in this process; herpes simplex virus 1 (HSV-1), in particular, is a strong suspect. We briefly summarize the data pointing at a pathogenic role for HSV-1 in the development of Alzheimer's disease and review results indicating that antiviral might be beneficial in the therapy of this condition.     

超声引导肝恶性肿瘤射频消融术与手术切除对细胞免疫影响的对比研究

目的探讨超声引导下射频消融术与手术切除术对肝癌患者外周血T淋巴细胞亚群的影响。方法应用流式细胞仪检测,30例以射频消融为治疗方式和30例以手术切除为治疗方式的原发性肝癌患者的术前、术后T淋巴细胞亚群的变化。结果射频组术后10d和20d外周血中CD3+、CD4+、CD4+/CD8+水平均明显高于术前水平,CD8+明显低于术前,差异均有统计学意义(均P0.05),且持续时间较长。手术组外周血中CD3+、CD4+、CD4+/CD8+水平明显低于术前水平,CD8+明显高于术前,差异均有统计学意义(P0.05)。射频组术后10 d和20 d外周血中CD3+、CD4+、CD4+/CD8+均明显高于手术组,CD8+明显低于手术组,差异均有统计学意义(均P0.05)。结论射频消融治疗肝癌患者细胞免疫功能增强,手术治疗则免疫细胞功能下降。射频消融在保护与改善细胞免疫功能方面强于手术治疗方法。     

T cell memory,anergy and immunotherapy in breast cancer

T cell immunity in breast cancer is suggested to play a role in tumor dormancy, a period of stability which can correspond to the time interval between primary treatment and tumor recurrence. Bone marrow in breast cancer patients seems to be particularly important because it is highly enriched with cancer specific memory T cells. Similar cells can be found in peripheral blood, but these appear to be functionally anergic. The immune system of primary operated breast cancer patients does not seem to be completely anergized. Bone marrow derived memory T cells can be reactivated ex vivo and show functional reactivity, including tumor rejection in NOD/SCID mice. Promising results were obtained from a postoperative phase-II active specific immunotherapy study. In this study, 32 patients treated with an optimal formulation of a virus-modified autologous tumor vaccine (ATV-NDV) appeared to have a significant 5-year survival benefit. Our results suggest that cancer reactive memory T cells which are enriched in the bone marrow of breast cancer patients, can be activated ex vivo via autologous dendritic cells pulsed with breast cancer tumor antigens, or they can be activated in situ via a tumor vaccine, which combines tumor antigens with virus infection. The findings should encourage further studies in breast cancer on active specific immunotherapy with tumor vaccines or adoptive immunotherapy with activated memory T cells.     

肾移植患者血清中可溶性B7-H3水平的变化及其临床意义

Objective To detect the serum soluble B7-H3 (sB7-H3) in patients before and after renal transplantation, and to investigate the clinical significance. Methods The serum level of sB7-H3 in 34 patients were determined before and 3, 6, 12 months after renal transplantation. Besides, 11 health adults were elected as controls. These 34 patients were divided into two groups according to HLA and/or MICA antibodies using Luminex before operation. After transplantation, all the patients were divided into two groups according to their conditions; group Ⅰ with rejection; group S with stable renal function and no rejection. Results The serum level of sB7-H3 in all 34 patients before operation was significantly higher than health controls [(27. 10 ± 13. 61) μg/L,n = 34 vs (11.61 ±3.77) μg/L,n = 11 ,P ＜0. 01], and significantly higher in patients with antibodies than in those without before operation [(34. 96 ± 17. 37) (μ/L, n = 11 vs (23. 34 ± 9. 75) (μg/L, n = 23, P ＜ 0. 05]. There was no significant difference in the serum level of sB7-H3 between control group and S group after operation (P ＞0. 05). In group Ⅰ, the serum level of sB7-H3 was increased obviously when rejection occurred [(20. 63 ±4. 28) μg/L,n = 12; (18. 95 ±2.98) μg/L,n=6; (28.36 ±19. 83) μg/L,n = 10] , as compared with group S and control group (P＜0. 01), while at the time without rejection, there was no difference among them (P ＞0. 05). Conclusion Monitoring serum sB7-H3 after renal transplantation would be clinically useful in indicating therapeutic effect and outcome of the patients.     

不同剂量X线照射对小鼠细胞免疫功能的影响

目的研究不同剂量X线照射对小鼠细胞免疫功能的影响.方法：75只8～10周龄BALB/C小鼠随机分为3组：A、B组分别应用直线加速器分别经2Gy和3Gy照射（X线）,C组为正常对照组,不接受照射.流式细胞仪测定第1～5周各组动物外周血T细胞亚群（CD3＋、CD4＋、CD8＋）及NK细胞（CD16＋CD56＋）的变化,并对脾及胸腺变化作病理学观察.结果：经照射的小鼠,其外周血T细胞亚群及NK细胞呈进行性降低,至第3、4周开始出现逐渐恢复迹象,4、5周后恢复正常.在同一时间,3 Gy照射较2 Gy照射所导致的细胞亚群降低的程度更为明显（P〈0.05）.脾、胸腺在照射后重量减轻并延续至4周才基本恢复至照射前的水平.观察5周各组未出现自然死亡.结论：BALB/C小鼠经照射后细胞免疫功能下降明显,4～5周后免疫功能恢复.     

瘢痕疙瘩形成机制的研究进展

瘢痕疙瘩是烧伤外科研究的重要课题，其形成机制尚未完全明确，本文就其在遗传机制、免疫作用、细胞增殖与胶原代谢、细胞因子等方面的研究进展进行综述。