猪到猕猴异种心脏移植超急性排斥反应的免疫学及病理学变化

目的观察猪到猕猴异种心脏移植超急性排斥反应时的免疫学及病理学变化。方法采用猪到猕猴腹腔内异位心脏移植模型,检测发生超急性排斥反应者的血液中补体、天然抗体及T淋巴细胞亚群的变化,并对移植心脏进行免疫组化(测定C3、C4、C5b9、IgG及IgM的沉积)及病理学分析。结果发生超急性排斥反应时,血清补体C3、C4的含量、总补体活性及抗猪内皮细胞天然抗体均有一定程度的下降;CD4 /CD8 T淋巴细胞的比率也有所下降;移植心脏中均有补体C3、C4、C5b9的沉积,IgG及IgM也均有沉积,但IgG和IgM沉积强度的差异无统计学意义;病理学改变主要为心肌间质弥漫性出血、水肿,毛细血管内普遍淤血。结论补体通过经典途径激活参与猪到猕猴异种心脏移植超急性排斥反应;超急性排斥反应时受者血中天然抗体水平明显下降;CD4 T淋巴细胞可能参与异种移植超急性排斥反应过程并有所消耗;发生超急性排斥反应的移植物突出病理表现为间质出血。     

异种表面角膜镜片术后外周血T细胞亚群和NK细胞活性的流式细胞仪分析

目的;研究异种表面角膜术后机体对异种角膜的免疫反应,阐明人体对异种角膜的免疫耐受机制。方法：应用流式细胞仪对９例接受异种表面角膜镜片术患者术后外周血Ｔ细胞的分布和自然杀伤细胞的活性进行了分析。结果;术后２个月,Ｔ细胞末被激活,ＮＫ活化程度显著提高,但未激发排斥反应。结论;猴角膜镜片虽可诱发轻微的免疫应答,但未达到增强抗原诱发的Ｔ细胞增殖应答的程度。     

Vertical ridge augmentation using an equine bone and collagen block infused with recombinant human platelet-derived growth factor-BB: a randomized single-masked histologic study in non-human primates

Background: This study tests the effectiveness of hydroxyapatite and collagen bone blocks of equine origin (eHAC), infused with recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB), to augment localized posterior mandibular defects in non‐human primates (Papio hamadryas). Methods: Bilateral critical‐sized defects simulating severe atrophy were created at the time of the posterior teeth extraction. Test and control blocks (without growth factor) were randomly grafted into the respective sites in each non‐human primate. Results: All sites exhibited vertical ridge augmentation, with physiologic hard‐ and soft‐tissue integration of the blocks when clinical and histologic examinations were done at 4 months after the vertical ridge augmentation procedure. There was a clear, although non‐significant, tendency to increased regeneration in the test sites. As in the first two preclinical studies in this series using canines, experimental eHAC blocks infused with rhPDGF‐BB proved to be a predictable and technically viable method to predictably regenerate bone and soft tissue in critical‐sized defects. Conclusion: This investigation supplies additional evidence that eHAC blocks infused with rhPDGF‐BB growth factor is a predictable and technically feasible option for vertical augmentation of severely resorbed ridges.     

The impact of successive infections on the lung microenvironment

The effect of infection history on the immune response is ignored in most models of infectious disease and in preclinical vaccination studies. No one, however, is naive and repeated microbial exposure, in particular during childhood, shapes the immune system to respond more efficiently later in life. Concurrent or sequential infections influence the immune response to secondary unrelated pathogens. The involvement of cross-reactive acquired immunity, in particular T-cell responses, is extensively documented. In this review, we discuss the impact of successive infections on the infected tissue itself, with a particular focus on the innate response of the respiratory tract, including a persistent alteration of (1) epithelial or macrophage expression of Toll-like receptors or adherence molecules used by subsequent bacteria to invade the host, (2) the responsiveness of macrophages and neutrophils and (3) the local cytokine milieu that affects the activation of local antigen-presenting cells and hence adaptive immunity to the next infection. We emphasize that such alterations not only occur during coinfection, but are maintained long after the initial pathogen is cleared. As innate responses are crucial to the fight against local pathogens but are also involved in the maintenance of the homeostasis of mucosal tissues, dysregulation of these responses by repeated infections is likely to have a major impact on the outcome of infectious or allergic disease.     

Impaired immune responsiveness in Plasmodium berghei immune mice

Mice immunized against Plasmodium berghei parasites by drug-controlled infection exhibited decreased immunoresponsiveness against rabbit red blood cells (RRBC). Increasing RRBC antigen dose increased responsiveness, but agglutinating anti-RRBC antibodies of the IgG class remained undetectable. Clearance of colloidal carbon from the bloodstream of malaria-immunized mice was not different from controls. Removal of all the persistent parasites from immune mice did not restore responsiveness until 140 days after treatment, suggesting that the parasite per se did not influence responsiveness directly. Because of this, and because of the fact that priming of mice with RRBC before P. berghei immunization was not more effective than priming after immunization, it was concluded that antigen uptake and subsequent presentation were not impaired in P. berghei immune mice, in contrast to infected mice. Anti-RRBC antibodies were detected in serum of P. berghei immune mice, but regulation of responsiveness to RRBC by transfer of such immune mouse serum was not found. Immunoglobulin levels, especially of the IgG2 and IgG3 subclass were elevated in sera of P. berghei immune mice, which indicated an LPS-like polyclonal activation. The results also suggest that during drug-controlled infection, which leads to immunity against infection, a state of B-cell tolerance is induced.     

微囊化大鼠胰岛异种移植的实验研究

目的　通过动物实验明确微囊化胰岛是否具有免疫隔离作用。方法　SD大鼠胰腺原位消化 ,Ficoll间断密度梯度离心法纯化、分离胰岛 ,气流吹喷制作海藻酸钠 /聚赖氨酸 /海藻酸钠(APA)微囊化大鼠胰岛 ,比较微囊化与未微囊化胰岛的胰岛素释放试验 ;将微囊化 (实验组 )与未微囊化 (对照组 )大鼠胰岛植入链脲佐菌素 (STZ)诱导的I型糖尿病小鼠中 ,作两组间血糖正常持续时间比较。结果　实验组与对照组的胰岛素释放试验差异无显著性 (P >0 .0 5 ) ;实验组血糖正常持续时间为 2 3～ 6 5d(平均 48d) ,对照组为 3～ 6d(平均 5d) ,两组差异有极显著性 (P <0 .0 1)。已排斥的实验组小鼠腹腔灌洗发现部分微囊化胰岛存活 ,部分已坏死 ,但微囊膜皆完整 ,囊壁无纤维化。结论　微囊具有良好的免疫隔离作用 ,可使胰岛移植物存活时间明显延长。同时推测微囊内移植物死亡与细胞因子、自由基作用或营养不足等有关。     

Heterologous fibrin sealant potentiates axonal regeneration after peripheral nerve injury with reduction in the number of suture points

The use of suture associated with heterologous fibrin sealant has been highlighted for reconstruction after peripheral nerve injury, having the advantage of being safe for clinical use. In this study we compared the use of this sealant associated with reduced number of stitches with conventional suture after ischiatic nerve injury. 36 Wistar rats were divided into 4 groups: Control (C), Denervated (D), ischiatic nerve neurotmesis (6 mm gap); Suture (S), epineural anastomosis after 7 days from neurotmesis, Suture + Fibrin Sealant (SFS), anastomosis with only one suture point associated with Fibrin Sealant. Catwalk, electromyography, ischiatic and tibial nerve, soleus muscle morphological and morphometric analyses were performed. The amplitude and latency values of the Suture and Suture + Fibrin Sealant groups were similar and indicative of nerve regeneration.The ischiatic nerve morphometric analysis in the Suture + Fibrin Sealant showed superior values related to axons and nerve fibers area and diameter when compared to Suture group. In the Suture and Suture + Fibrin Sealant groups, there was an increase in muscle weight and in fast fibers frequency, it was a decrease in the percentage of collagen compared to group Denervated and in the neuromuscular junctions, the synaptic boutons were reestablished.The results suggest a protective effect at the lesion site caused by the fibrin sealant use. The stitches reduction minimizes the trauma caused by the needle and it accelerates the surgical practice. So the heterologous fibrin sealant use in nerve reconstruction should be considered.     

Plant as Bioreactor for Producing Heterologous Proteins

Using plants to produce heterologous proteins makes it very attractive due to the potentially low costs. Using this procedure it is possible to produce medicinal protein for clinical applications with the plants bioreactors increasing gradually. The paper proposes the five major systems of the plant bioreactor as well as their advantage and disadvantage and the development of each system. Focuses on the five major systems of the plant bioreactor to produce vaccines, antibodies and medical protein and the research achievement at the present stage and the research on my laboratory. The key technology research of plant bioreactor such as new genes, new biological components,new technologies and new research methods related with plant bioreactor offer a work foundation for a long-term development in future.     

Enhanced immunogenicity and antitumour effects with heterologous prime-boost regime using vaccines based on MG7-Ag mimotope of gastric cancer

MG7-Ag, gastric cancer-associated antigen, has been shown to be immunogenic and has been used as marker molecule for prognosis. In a previous study, we developed an oral DNA vaccine based on MG7-Ag mimotope. However, we failed to detect cellular immune response using the oral MG7-Ag mimotope DNA vaccine. To induce significant T cell response, we developed a recombinant adenovirus vaccine based on MG7-Ag mimotope and evaluated the efficacy and protective effects of heterologous prime-boost immunization protocol with an oral DNA vaccine previously developed. We found that both vaccines were able to elicit a significant humoral response against MG7-Ag, while the highest serum titre MG7 antibody was detected in mice immunized with the heterologous prime-boost immunization protocol. Enzyme-linked immunospot (ELISPOT) assay demonstrated that the heterologous prime-boost immunization strategy was more efficient in inducing T cell response than the homologous prime-boost strategy. In the tumour challenge assay, 2 of 5 mice immunized with the heterologous prime-boost protocol were tumour free, while none of the mice in homologous prime-boost groups or control groups was tumour free. Those tumour-bearing mice in the heterologous prime-boost regime had smaller tumour masses than their counterparts in the homologous prime-boost groups or control groups. Therefore, our study suggests that vaccines against MG7-Ag induce significant immune response against gastric cancer, and that the heterologous prime-boost protocol using different types of vaccines could achieve better protective effect than the homologous prime-boost protocol.     

Concurrent detection of human herpesvirus type 6 and measles-specific IgMs during acute exanthematic human parvovirus B19 infection

A familial outbreak of human parvovirus B19 infection is described in which serological tests carried out routinely for determining the causal agent of febrile rashes of viral etiology failed to yield a definitive diagnosis. Concurrent detection of serum IgMs to parvovirus B19 and to heterologous viruses such as human herpesvirus type 6 (HHV-6) and measles virus complicated interpretation of the data. IgG avidity tests and investigation and testing for the presence of viral DNA in sera by PCR were required to confirm parvovirus B19. The study stresses the importance of avidity and PCR tests to obtain a firm diagnosis of febrile exanthematic viral diseases.