胸腺内注射异基因抗原诱导鼠异体骨移植的免疫耐受

背景:同种异体骨同其他异体组织一样具有抗原性,移植后可引起以细胞免疫为主的排斥反应,应用免疫抑制剂可抑制免疫排斥反应的发生,但对机体有一定的不良影响。目的:探讨胸腺内注射异基因抗原在建立特异性骨移植免疫耐受中的作用。方法:取60只Wistar大鼠随机分为3组,均制作骨缺损模型,供体异基因胸腺内注射组于同种异体骨移植前胸腺内注射受体大鼠脾细胞MHC抗原,同时另设自体骨移植组、同种异体骨移植加用免疫抑制剂组为对照,移植后观察切口情况。移植后1,2,4,6周进行X射线检查,苏木精-伊红染色,可溶性白细胞介素2受体、混合淋巴细胞培养免疫学检测。结果与结论:大体表现、X射线及组织学检查见供体异基因胸腺内注射组、自体骨移植组表现相近,均有炎性细胞浸润及新骨形成。同种异体骨移植加用免疫抑制剂组再生血管较少,骨愈合延迟,炎性细胞浸润明显,移植骨逐渐吸收,无新骨形成。证实了异基因MHC抗原注入小鼠胸腺内,能成功诱导受体对供体鼠骨移植物的耐受。免疫学检查各项数据表明供体异基因胸腺内注射的成骨效果接近于自体骨移植组,优于同种异体骨移植加用免疫抑制剂,证实了胸腺内注射异体MHC抗原可诱导对供体骨移植物的免疫耐受。     

异体骨移植材料的研究现状及进展

1880年Macewen首先施行了人类同种异体骨移植术,本世纪四十年代末建立了骨库,骨移植已成为仅次于输血最常用的移植术。同种异体骨移植与实质脏器移植有所不同,诱发的宿主免疫排异反应一般不引起危及生命的严重后果,但免疫排异反应往往干扰移植骨愈合,影响治疗效果。     

同种异体骨移植后T淋巴细胞的分布与变化

背景：研究表明体液免疫在同种异体骨移植免疫排斥反应中不起主要作用,目前一般认为细胞免疫在排斥反应中起主导作用。 目的：概述同种异体骨移植后T淋巴细胞的分布与变化。 方法：采用电子检索的方式,在万方数据库(http://www.wanfangdata.com.cn/)、Pubmed数据库(http:// www.ncbi.nlm.nih.gov.pubmed/)中检索1990-01/2011-12关于同种异体骨移植后T淋巴细胞的分布与变化的文章,关键词为“骨移植,同种异体,T淋巴细胞”。排除重复研究、普通综述或Meta分析类文章,筛选纳入31篇文献进行评价。 结果与结论：同种异体骨移植后,体内抑制T淋巴细胞被激活,对免疫排斥反应起负反馈调节作用,T淋巴细胞发生显著变化;但深低温冷冻、冷冻干燥、γ射线辐照、复合免疫抑制剂等方法可以有效降低其免疫原性及疾病传播的风险。大量研究认为,同种异体骨具有骨组织的完整性结构、机械稳定性、生物学活性、骨诱导能力和极低的免疫性以及与宿主骨有较强的愈合能力等优点,植入体内后通过全方位再血管化、新骨形成、异体骨与宿主骨连接而实现生物学骨掺入过程。提示同种异体骨是一种可行的移植材料,可作为目前修复骨缺损的重要手段之一。      

同种异体骨移植用于骨缺损修复的应用现状

背景：创伤、感染和骨种瘤等原因导致的骨缺损难以自身愈合,目前治疗主要以骨移植为主。同种异体骨移植与实质脏器移植有所不同,诱发的免疫排斥反应相对较小,在临床上得到广泛应用。 目的：总结中国同种异体骨移植治疗骨肿瘤、创伤性骨缺损和脊柱病变的现状。 方法：应用计算机检索PubMed 数据库及中国期刊网全文数据库1983-01/2011-10 有关同种异体骨移植在各种骨科疾病中应用的文章,英文检索词为“bone allograft; bone transplantation; repair; bone defect”,中文检索词为“同种异体骨,骨移植,修复,骨缺损”。排除重复性及非中英文语种研究,共保留27篇文献进行综述。 结果与结论：同种异体骨移植作为临床上修复骨缺损的方法,广泛用于骨折、骨肿瘤切除后导致骨缺损的修复、脊柱和关节疾患的治疗。虽然同种异体骨移植存在细菌和病毒感染、骨折、不愈合、延迟愈合等危险,但是由于它在修复骨缺损时具有的一些优点：结构类似于自体骨,排斥反应较异种骨轻,而且不存在自体骨移植引起的供区损伤、延长手术时间等问题,使其成为修复骨缺损的常用材料。      

带血管同种异体骨移植研究进展

如何解决肢体大段骨缺损是骨科领域的研究重点和难点,带血管同种异体骨移植是解决该难题颇具潜力的方法.本文着重探讨了带血管同种异体骨移植的抗原,免疫抑制剂的使用,带血管骨深低温冷冻技术,及其临床运用,展示骨移植现状,为进一步研究和实践提供一定借鉴.     

带血管同种异体骨移植研究进展

如何解决肢体大段骨缺损是骨科领域的研究重点和难点，带血管同种异体骨移植是解决该难题颇具潜力的方法。本文着重探讨了带血管同种异体骨移植的抗原、免疫抑制剂的使用，带血管骨深低温冷冻技术及其临床运用，展示骨移植现状，为进一步研究和实践提供一定借鉴。     

同种异体骨移植去抗原和灭菌处理

同种异体骨移植是治疗骨缺损最常采用的方法。对供体骨进行除抗原和灭菌处理是提高同种异体骨移植临床治疗效果和确保安全性的必要措施。本文就同种异体骨移植常用的去抗原和灭菌处理方法现状作一简要介绍。     

硫贲妥钠对小鼠红细胞免疫功能的影响

目的 观察静脉麻醉药硫贲妥钠对小鼠红细胞免疫功能的影响。方法 采用郭峰法红细胞C3b受体花环、免疫复合物花环实验和直向肿瘤红细胞花环试验测定红细胞免疫粘附功能。结果 麻醉组与对照组比较红细胞C3b受体花环率及肿瘤红细胞花环率统计学具具有显著差异，红细胞免疫复合物花环率无显著差异。结论 硫贲妥钠麻醉抑制小鼠红细胞免疫功能。     

同种异体松质骨移植的生物力学研究

目的：探讨同种异体松质骨移植后的力学性能变化以及不同力学环境对其的影响。方法：在40只家兔前肢尺骨中段进行同种异体松质骨移植，并使左右侧植骨块分别承受正常生理载荷与低载荷，动物分批处死后取出植骨区标本进行骨密度值、三点弯曲、平均骨小梁厚度等测试。结果：同种异体松质骨愈合时的骨密度值、最大弯矩、平均骨小梁厚度逐渐上升。在移植后第16周时，和低载荷侧比较，正常载荷侧的上述指标都明显优于低载荷侧（P值分别＜0.01，0.05，0.05）。结论：同种异体松质骨移植后的力学性能变化与它所承受的载荷大小有较强的相关性。     

红细胞免疫功能的测定在恶性血液病病人中的应用及其临床意义

目的 :了解恶性血液病病人红细胞免疫功能状况。方法 :采用红细胞酵母菌花环试验检测 40例恶性血液病患者红细胞免疫功能。结果 :红细胞C3b受体花环率 (RCR)及红细胞促中性粒细胞吞噬率(ERPN)显著下降 ,红细胞免疫复合物花环率 (RICR)和C3b受体花环抑制率 (RFIR)显著升高 ,而红细胞C3b受体花环增强率 (RFER)显著降低。结论 :恶性血液病患者存在红细胞免疫功能继发性损害 ,急性白血病缓解期红细胞免疫功能有所恢复 ,但仍较对照组低 (P <0 .0 5 )。恶性淋巴瘤及多发性骨髓瘤缓解红细胞免疫功能基本恢复正常     

On the possible origin of extra-epithelial enterochromaffin cells by budding from the crypts of Lieberkuhn

This study was undertaken to test Pierre Masson's still unconfirmed theory that extra-epithelial enterochromaffin cells in the gut arise in adult life by budding from the crypts of Lieberkuhn under conditions of low grade inflammation. Appendices (900) were reviewed and 19 were selected for serial section study because in random sections they showed lateral fusion of the crypts, one of the key features described by Masson. Ten specimens without crypt fusion served as controls. Sixteen of the 19 study specimens and one of the control specimens showed budding, averaging one bud in every 88 sections. Most buds were in direct contact with Schwann cells in the adjacent lamina propria and 45 per cent of them contained enterochromaffin cells. There was also histologic evidence linking buds and lateral crypt fusion to low grade inflammation. Masson's ideas are, therefore, confirmed insofar as the existence of buds and their relationship to enterochromaffin cells, Schwann cells, and inflammation is concerned. The actual separation of buds from the crypts to form extra-epithelial enterochromaffin cells has yet to be proved.     

大鼠肝卵圆细胞的诱导、分离及鉴定

目的建立大鼠肝卵圆细胞的增殖模型,并探索其分离及鉴定方法。方法雄性Wistar大鼠每天1次连续灌胃给予不同剂量二乙酰氨基芴(2-AAF熏5、10、15、20、25mg/kgBW),第5天行标准的2/3肝切除术,术后按各自剂量继续给予11天,不同时间取肝脏组织,行甲胎蛋白、细胞角蛋白18及19染色并观察。以确定的2-AAF最佳剂量制备大鼠肝干细胞增殖模型,Seglen胶原酶原位灌注结合Percoll密度梯度离心分离纯化大鼠肝卵圆细胞,光镜、电镜下观察细胞特点,并进行上述细胞表型标志免疫组化染色。结果2-AAF15mg/kgBW能建立较理想的肝卵圆细胞增殖模型。HE染色可见汇管区及中央静脉周围大量增殖的嗜碱性小细胞,电镜下观察此种细胞具有卵圆形细胞核、细胞质少而淡、核/浆比例较大等特点,免疫组化染色证实甲胎蛋白、细胞角蛋白18和19染色阳性,白蛋白及白细胞共同抗原(LCA)染色阴性。分离所得底层细胞,光镜下表现大小不等、不规则圆形细胞,体积较小,细胞核/浆比例较大,电镜下细胞表面可见少量短而小的微绒毛状突起,余同增殖细胞特点,免疫组化染色与增殖细胞表现相同细胞表型特点。结论本方法可成功诱导、分离、纯化大鼠肝卵圆细胞,符合肝卵圆细胞的形态特点、超微结构及细胞表型标志特点。     

两种不同纯度的嗅鞘细胞在体外存活与生长的比较

比较80%和50%两种纯度的嗅鞘细胞在体外培养条件下的存活与生长,为嗅鞘细胞体内移植选用最佳纯度提供依据。分离、培养并纯化成年SD大鼠嗅鞘细胞,将纯化的嗅鞘细胞和收集到的贴壁成纤维细胞进行约80%和50%的比例混合后接种,继续培养1d或3d。所有细胞于不同时间点行P75免疫细胞化学荧光染色,以鉴定嗅鞘细胞的初始及其后培养过程中数量和纯度的变化。观察细胞状态,计数细胞总数和P75免疫阳性细胞数目,求得各组嗅鞘细胞数量和纯度并行统计学分析。结果显示:两种不同纯度嗅鞘细胞在培养1d时形态正常,3d时纯度为50%的嗅鞘细胞胞体依然饱满,突起更加纤长,数量和纯度亦无明显下降。而纯度为80%的嗅鞘细胞在培养3d时已出现胞体萎缩和突起变短,数量从1d时每一观察区域内的35±13显著下降为23±5(P=0.02),但纯度未发生明显变化。结果表明50%纯度嗅鞘细胞的存活及生长状态优于80%者,提示细胞体内移植时应考虑选取50%纯度的嗅鞘细胞。     

Diversity of tissue-resident NK cells

Although natural killer (NK) cells were initially named for their spontaneous tumor-killing capacity, their concept has been greatly expanded with more than 40 years of extensive investigation. Currently, NK cells are known as a heterogeneous population of innate lymphoid cell (ILC) family, consisting of different subsets with unique phenotypic and functional features. Recent studies have shown that tissue-resident NK (trNK) cells, which are distinct from conventional NK (cNK) cells, preferentially distribute in non-lymphoid tissues, such as the liver, uterus, salivary gland, and adipose. In this review, we provide a comprehensive overview of the current knowledge about the phenotype, function and development of trNK cells across different tissues and describe the similarities and differences between diverse trNK cells and cNK cells, with a particular focus on the tissue-specific characteristics of different trNK cells.     

The molecular makeup and function of regulatory and effector synapses

Summary:  Physical interactions between T cells and antigen-presenting cells (APCs) form the basis of any specific immune response. Upon cognate contacts, a multimolecular assembly of receptors and adhesion molecules on both cells is created, termed the immunological synapse (IS). Very diverse structures of ISs have been described, yet the functional importance for T-cell differentiation is largely unclear. Here we discuss the principal structure and function of ISs. We then focus on two characteristic T-cell–APC pairs, namely T cells contacting dendritic cells (DCs) or naive B cells, for which extremely different patterns of the IS have been observed as well as fundamentally different effects on the function of the activated T cells. We provide a model on how differences in signaling and the involvement of adhesion molecules might lead to diverse interaction kinetics and, eventually, diverse T-cell differentiation. We hypothesize that the preferred activation of the adhesion molecule leukocyte function-associated antigen-1 (LFA-1) and of the negative regulator for T-cell activation, cytotoxic T-lymphocyte antigen-4 (CTLA-4), through contact with naive B cells, lead to prolonged cell–cell contacts and the generation of T cells with regulatory capacity. In contrast, DCs might have evolved mechanisms to avoid LFA-1 overactivation and CTLA-4 triggering, thereby promoting more dynamic contacts that lead to the preferential generation of effector cells.     

人羊膜上皮细胞上清液对人肝癌BEL-7402细胞的体外抗肿瘤作用

目的探讨人羊膜上皮细胞(h AECs)上清液对体外培养的肝癌细胞系BEL-7402细胞迁移、增殖与凋亡的影响。方法 BEL-7402细胞随机分为5组,其中对照组不加h AECs上清液,其余4组加入体积分数分别为6.25%、12.5%、25%和50%的h AECs上清液作用24 h后,通过划痕实验、MTT试验和流式细胞术检测BEL-7402细胞迁移、增殖和凋亡;Western blot法检测凋亡相关蛋白的表达量。结果 h AECs上清液能剂量依赖性地抑制BEL-7402细胞迁移、增殖并诱导凋亡(P0.05);25%和50%h AECs上清液组BEL-7402细胞caspase-3和caspase-8蛋白的切割片断蛋白定量明显高于对照组(P0.05)。结论 h AECs上清液对体外培养的BEL-7402细胞具有一定的抗肿瘤作用。     

人外周血树突状细胞-乳腺癌细胞融合细胞

目的：探讨树突状细胞—肿瘤细胞融合细胞的形态特性，为研制融合细胞疫苗提供形态学依据。方法：将免疫磁珠法分离的人外周血树突状细胞与人乳腺癌细胞株MCF7融合，瑞氏—姬姆萨染色观察；扫描电镜观察树突状细胞、融合细胞的表面超微结构。结果：树突状细胞与MCF细胞按10：1比例融合后，一个乳腺癌细胞可以与一个或多个树突状细胞相融合；扫描电镜下可见分离的树突状细胞表面有突起，树突状细胞/MCF7融合细胞具两种亲代细胞的表面超微结构特点。结论：树突状细胞与人乳腺癌细胞融合后无明显的形态改变。     

Harnessing innate and adaptive immunity for adoptive cell therapy of renal cell carcinoma

The development of immunotherapies for renal cell carcinoma (RCC) has been the subject of research for several decades. In addition to cytokine therapy, the benefit of various adoptive cell therapies has again come into focus in the past several years. Nevertheless, success in fighting this immunogenic tumor is still disappointing. RCC can attract a multitude of different effector cells of both the innate and adaptive immune system, including natural killer (NK) cells, γδ T cells, NK-like T cells, peptide-specific T cells, dendritic cells (DC), and regulatory T cells (Tregs). Based on intensive research on the biology and function of different immune cells, we now understand that individual cell types do not act in isolation but function within a complex network of intercellular interactions. These interactions play a pivotal role in the efficient activation and function of effector cells, which is a prerequisite for successful tumor elimination. This review provides a current overview of the diversity of effector cells having the capacity to recognize RCC. Aspects of the functions and anti-tumor properties that make them attractive candidates for adoptive cell therapies, as well as experience in clinical application are discussed. Improved knowledge of the biology of this immune network may help us to effectively harness various effector cells, placing us in a better position to develop new therapeutic strategies to successfully fight RCC.     

Transitional cell carcinoma of the urinary bladder with osteoclast-type giant cells: a report of two cases and review of the literature

We report two transitional cell carcinomas of the urinary bladder containing numerous osteoclast-type giant cells that stained for vimentin and acid phosphatase (with and without tartrate) and were negative for cytokeratin and lysozyme. One tumour, in a 65-year-old man, was composed of papillary transitional cell carcinoma, invasive poorly differentiated carcinoma with a prominent spindle cell component and numerous osteoclast-type giant cells; repeat curettage 2 months later showed no residual tumour. The second tumour occurred in a 75-year-old woman who underwent a radical cystectomy for a deeply invasive transitional cell carcinoma with a spindle and anaplastic giant cell component and areas containing numerous osteoclast-type giant cells. Osteoclast-type giant cells, which appear to be reactive, should be distinguished from the neoplastic giant cells of giant cell carcinoma.