Tregs对同种异体牙移植免疫排斥反应的抑制作用

目的 探讨Tregs对同种异体牙移植术后免疫排斥反应的抑制作用,提供一种免疫移植方法.方法 免疫抑制剂Tregs给予白鼠尾巴静脉注射1周,建立白鼠同种异体牙移植模型,术后观察移植牙存活、排异发生率及程度.结果同种异体牙均诱发免疫排斥反应,但Tregs注射后免疫排斥反应的时间缓慢,组织切片存活时间显著延长（P＜0.01）.结论 使用免疫抑制剂是预防同种异体牙移植免疫排斥反应的有效方案,可以使同种异体牙移植免疫排斥反应延迟,存活时间延长.     

同种异体骨移植的免疫排斥

一、 同种异体组织免疫排斥的原理 同种异体组织 (简称同种组织 )免疫排斥反应是由供体组织 MHC抗原引起的宿主对同种异基因供体组织的免疫攻击,主要通过 T细胞介导的细胞免疫来完成。人类的 MHC抗原称为 HLA抗原,与移植排斥有关的是主要分布在白细胞表面的 HLA－Ⅰ 类抗原和主要分布在 B细胞、巨噬细胞和树突状细胞表面的 HLA－Ⅱ 类抗原。 HLA的高度多态性使无关个体间的 HLA型别不会完全相同,因而对同种组织有不同程度的排斥反应。 参与免疫排斥的细胞根据其功能分为三类：抗原呈递细胞 (antigen presenting cell, APC),…     

同种异体复合组织移植的免疫研究进展

目的了解同种异体复合组织移植的免疫研究进展。方法查阅相关文献,对同种异体复合组织移植的免疫特点、实验进展、临床经验等进行总结。结果同种异体复合组织位于体表,包含组织成分复杂,抗原性高。其移植后在免疫抑制剂用药方案、排斥反应的诊断以及慢性排斥反应发生率等许多方面同内脏器官移植有不同的特点。结论在下一步研究中,应吸取同种异体复合组织移植独特的经验教训,在诱导耐受、局部用药、排斥诊断等方面树立同种异体复合组织的独特标准。     

大鼠同种异体股动脉移植后的免疫学研究

以两个近交系大鼠间股动脉移植为模型，观察单纯血管移植后宿主细胞和体液免疫指标的变化，以及移植血管局部的病理变化，探讨单纯血管因素对宿主免疫状态的影响及其在移植排斥中的作用。结果显示，同种异体股动脉移植足以引起的宿主主全身性珠免疫应签反应，导致移植血管的排斥，排斥反应于移植后２－４周最为强烈，细胞和体液免疫因素同时参与。     

移植物处理减轻同种异体移植后排斥反应的研究进展

同种异体移植是当今医学界应用最多的移植类型,其术后的排斥反应是影响移植物功能和长期存活的主要因素。近年来,许多研究表明,多种因素影响移植术后的排斥反应,其中,对移植物进行适当的保存和处理可能会降低移植后排斥反应的强度。本文就异体移植后排斥反应的免疫机制、移植物的处理方法进行综述。     

同种异体骨髓基质细胞肌肉内成骨分化的实验研究

目的 观察并探讨同种异体兔骨髓基质细胞在未接受免疫抑制剂的正常兔肌肉内移植后的免疫原性、存活及成骨状况.方法 首先通过兔谱系差异选择供、受体,并采用淋巴细胞反应进一步证实免疫学错配,之后抽取兔骨髓、体外分离培养、获取骨髓基质细胞,体外加矿化条件培养液诱导成骨、并对成骨特性予以鉴定后,将异体骨髓基质细胞移植入受体兔肌肉内,从淋巴细胞转化率、淋巴细胞杀伤活性、组织学检查、种子细胞体内成活及成骨情况等方面检测. 结果 术后各检测时间,异体骨髓基质细胞移植未诱发淋巴细胞大量增殖反应(P>0.05),淋巴细胞杀伤活性与自体组差异无统计学意义(P>0.05),移植区未见到大量炎性细胞浸润,经组织学及免疫组化染色证实异体骨髓基质细胞在受体组织内存活,8周后于异体肌肉中形成骨组织. 结论 同种异体骨髓基质细胞移植,未诱发免疫排斥反应,在无免疫抑制剂应用的情况下,移植细胞在受体肌肉内存活、并形成骨性组织.     

凝血酶与移植物内皮细胞损伤

随着移植免疫基础理论的研究和进展、实验手段及移植配型等方法日臻完善、以及免疫抑制剂的成功应用 ,有效降低了抗宿主排斥反应 ,器官移植后的存活率等方面取得卓著成绩。人们转而逐渐认识到移植后的血栓并发症 ,以及由凝血酶 (ｔｈｒｏｍｂｉｎ/Ⅱα)等凝血相关因子、细胞因子、粘附分子、趋化因子等相互作用 ,介导移植物内皮细胞损伤、血管平滑肌增生、纤维素沉积等一系列病理变化 ,已成为导致移植失败的重要原因。本文将着重对同种异体移植后急性排斥反应中凝血酶参与介导的内皮细胞损伤机制作一综述。一、凝血酶的形成、主要生物学特性…     

深低温冻储在大鼠同种异体气管移植中免疫抑制作用

目的探讨深低温冻储在同种异体气管移植中的作用.方法选择近交系Lewis大鼠自体气管移植(L-L组),及F344和Lewis行未冻储(F-L组)、冻储(CF-L组)同种异体气管移植,分别在术后2、7、30天观察各组移植段光镜下免疫排斥反应变化.结果①CF-L组在移植术后各时间点与F-L组相比较,炎细胞浸润程度及上皮下组织增殖相比显著降低(P＜0.05).②CF-L组PBMC内γ-IFN表达量在术后2、7、30天均明显低于F-L组(P＜0.01).③F-L组在移植术后2、7、30天,凋亡细胞计数均较L-L组和CF-L组高(P＞0.05).结论深低温冻储可能通过调节同种异体气管移植术后Th型细胞因子的变化和移植物细胞凋亡,从而抑制了免疫排斥反应.     

冻干和辐照对同种异体血管免疫原性的影响

探讨冻干和辐照处理对同种异体血管免疫原性的影响。方法以两个近交系大鼠间同种异体血管移植为模型，比较新鲜和制备血管移植后宿主细胞和体液免疫状态的变化，以及移植血管的病理变化。结果 与新鲜的同种异体血管相比，处理血管移植后不引起宿主的急性排斥反应。     

转化生长因子β1质粒对新鲜异体神经移植排斥反应的影响

自体神经移植是目前修复周围神经缺损的最佳方式,但存在增加手术创伤、造成供体神经支配区域的功能障碍及供体有限等缺点.同种异体神经移植可克服这一困难,但存在免疫排斥反应,移植后的免疫排斥反应是影响神经移植效果的重要因素[1].如何有效地抑制或减弱移植排斥反应是提高移植成功率,延长存活时间的根本问题.转化生长因子-1(TGF-β1)是一种强效细胞生长增殖调节蛋白,在移植免疫的抗排斥反应中扮演重要角色,已成为近年细胞,组织,器官移植的研究热点.我们通过局部注射TGF-β1质粒,观察其对大鼠异体神经移植后排斥反应的影响.     

Cyst fluid of glioma does not inhibit the killing action of lymphokine-activated killer (LAK) cellsin vitro

Summary In theory, lymphokine-activated killer (LAK) cells offer a potential method to treat cerebral gliomas, especially low-grade gliomas. LAK cells would be administered by repeated injections straight into the cavity of a subtotally removed tumour. However, brain-tumour cyst fluid has been shown to be immunosuppressive in lymphocyte stimulation tests. Therefore we wanted to know whether the fluid would reduce the killing efficacy of LAK cells. Using a standard cytotoxity test based on⁵¹Cr release, we comparedin vitro the cytotoxity of LAK cells against K-562 tumour cells in brain-tumour cyst fluid, autologous serum and allogeneic serum. Five patients with cystic glioma and one with cystic meningioma were studied and no inhibition of cytotoxity of LAK cells was observed.     

Cytopenias following kidney transplantation

Cytopenias frequently occur during the first months after solid organ transplantation. Many mechanisms are involved but drugs toxicity and infections are the major causes of cytopenias. Anemia is also related with chronic kidney graft dysfunction. Several drugs are pointed out but antithymocyte globulin, antiproliferative drugs and antiviral drugs are mainly responsible for cytopenias. Infectious causes are mainly viral and can rarely induce macrophage activation syndromes. Passenger lymphocyte syndrome is only described after ABO incompatible transplantations. Thrombotic microangiopathies are frequent and multifactorial (antibody mediated rejection, calcineurine inhibitors toxicity, infections, initial nephropathy recurrence). Cytopenias following transplantation increase the risk of infectious disease by neutropenia and generally lead to an immunosuppressive therapy reduction. It seems to increase the risk of rejection when the baseline immunosuppressive level is not further restored.     

Gastrointestinal side effects of mycophenolic acid in renal transplant patients: a reappraisal.

Patient and graft survival following renal transplantation have improved markedly over the past decade, meaning that physician attention has turned more towards minimizing short- and long-term toxicities associated with immunosuppressive regimens. Gastrointestinal (GI) adverse events are common following renal transplantation and all immunosuppressive regimens have been associated with such events. Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) are potential components of immunosuppression regimens, and are associated with the most successful outcomes in kidney transplantation. The effects of MMF and EC-MPS are likely mediated via the active metabolite mycophenolic acid (MPA). The GI events caused by both MMF and EC-MPS may, in part, be related to MPA, independent of the formulation or route of administration. MPA may produce GI events either through direct action or through the action of it metabolites. However, many other factors may cause GI events observed following renal transplantation. These include the surgery itself and concurrent diseases such as diabetes, and bacterial, viral, fungal and parasitical infections. Additionally, numerous concomitant non-immunosuppressive agents, including antibiotics hypoglycaemic and proton-pump inhibitors, can be associated with GI events. In a recent trial in renal transplant patients with severe diarrhoea, approximately 50% of patients achieved resolution of diarrhoea through methods other than altering their immunosuppressive regimens. Indeed altering of the immunosuppressive regimen may lead to the risk of acute rejection. Thus, in order to reduce the risk of rejection and subsequent damage to the graft, it is important to consider other causes of GI events in renal transplant patients before altering immunosuppressive regimens.     

Natural killer cells and lung transplantation, roles in rejection, infection, and tolerance

Despite improvements in surgical technique, organ preservation, immunosuppression, and management of infection, the long term survival following lung transplantation remains low, mainly due to immune mediated complications such as acute and chronic rejection. Almost all immunosuppressive agents used in the prophylaxis and treatment of rejection following lung transplantation are targets of T cell maturation, function or proliferation, which in theory should cause sufficient disruption of the adaptive immune system to prevent graft rejection. However the five year survival rate of only 50% suggests this is not the case. More recent evidence suggests that NK cells may play a significant role in immune processes following lung transplantation. This article reviews the literature on the potential function of NK cells in rejection, infection, malignancy and tolerance following lung transplantation.     

肝联合其他器官移植术后近期免疫抑制策略的方案探讨

目的探讨肝联合其他器官移植术后近期的免疫抑制策略。方法我中心于2004年至2009年共实施肝联合其他器官移植22例,其中肝肾联合移植17例,肝胰十二指肠联合移植5例。存活时间大于3个月的患者共18例,比较此类患者与单一器官移植患者术后近期排斥反应发生率和免疫抑制策略的差别。结果肝联合其他器官移植的患者术后3个月内,移植肝排斥反应发生率为5．5％;移植肾的排斥反应发生率为5．9％;其他器官没有发生排斥反应,较我中心单一器官移植排斥反应发生率低。同时,肝联合其他器官移植患者免疫抑制剂初始剂量及术后近期所需浓度均较单一器官移植低。结论肝联合其他器官移植的患者,由于移植肝对其他移植器官的免疫保护作用,排斥反应发生率低,所需免疫抑制剂初始剂量及浓度均低于单一器官移植。但肝脏对其他移植器官的免疫保护作用机制尚需进一步研究。     

肾移植术后血清抗MICA抗体与慢性排斥反应的相关性

目的 探讨肾移植受者的抗MICA抗体水平与慢性排斥反应的相关性及其对移植肾功能的影响.方法 共有105例受者被作为研究对象纳入分析,其中发生慢性排斥反应者(慢排组)43例,移植肾功能正常者(对照组)62例.记录两组受者术前群体反应性抗体(PRA)、HLA抗原错配数、供肾冷缺血时间、出院时血清肌酐(SCr)水平、术后免疫抑制方案以及入组时间(入组时距肾移植手术时间)等资料,并进行比较.受者分组后,抽取受者外周血,检测SCr及抗MICA抗体水平,抗MICA抗体的检测采用Luminex 100免疫磁珠流式细胞仪技术.观察与比较抗MICA抗体阳性受者和抗MICA抗体阴性受者间术后3个月内发生急性排斥反应(AR)的次数和移植肾功能的差异.移植肾功能的评价采用血清肌酐变化率(△SCr/M),即(入组时SCr值-出院时SCr值)/入组时间.结果 两组受者在性别、年龄、HLA抗原错配数、供肾冷缺血时间、术后免疫抑制方案、出院时SCr水平及入组时间的比较,差异均无统计学意义(P＞0.05).分组后,慢排组受者SCr水平和抗MICA抗体阳性受者比例均明显高于对照组,两组比较,差别均有统计学意义(P＜0.01,表1).抗MICA抗体阳性受者术后3个月内发生的AR次数明显多于抗MICA抗体阴性受者,二者比较,差异有统计学意义(P＜0.05).抗MICA抗体阳性受者的△SCr/M为8.3±3.6,明显高于抗MICA抗体阴性受者的2.4±2.6,二者比较,差异有统计学意义(P＜0.05).结论 抗MICA抗体的表达与慢性排斥反应的发生相关,移植前进行MICA配型可减少术后移植肾慢性排斥反应的发生,有助于延长移植肾的长期存活.     

猪异位肝移植术中血流动力学特点

目的 观察猪异位肝移植术中血流动力学变化特点。方法 采用同窝猪建立右肝下异位肝移植模型,从右颈浅静脉切开插管,监测心率(HR)、平均动脉压(MAP)、心排出量(CO)、体循环阻力(SVR)、肺循环阻力(PVR)、中心静脉压(CVP)、肺动脉楔压(PAWP)、平均肺动脉压(MPAP)等血流动力学指标,观察异位肝移植术中血流动力学变化规律。结果 门静脉开放后HR明显升高、MAP下降(P<0.01),CO、SVR、PVR轻度增加,幅度不大(P>0.05);开放腹主动脉后MAP下降(P<0.01);CVP、PAWP、MPAP等于术中各期均无明显变化。结论 猪异位肝移植术中血流动力学变化的特点是：门静脉开放再灌注后HR明显升高、MAP下降。     

The emerging role of rituximab in organ transplantation

Long-term acceptance of solid organ allografts remains a challenge. While many acute rejection episodes can be treated, new mechanisms of allograft damage are now being defined especially in kidney transplantation. Unexpected clusters of CD20(+) cells have been discovered in renal biopsies performed for clinical rejection. C4d deposition is now routinely seen in refractory rejection. Despite the rapid introduction of new immunosuppressive agents in transplantation, the search for an efficacious anti-B-cell agent remains. With novel mechanisms of allograft damage now being defined, it is important to consider how an anti-B-cell agent might fit into an immunosuppressive regimen. Rituximab is a high-affinity CD20 specific antibody that depletes the B-cell compartment by inducing cellular apoptosis. Thus, it is a rational choice for therapy in transplantation to abrogate B-cell mediated events. In this review, we will discuss the mechanisms of action of rituximab, and its use in for a variety of indications in solid organ transplantation. There are emerging case reports that show that rituximab may be an effective agent to treat antibody-mediated rejection, and post-transplant lymphoproliferative disorder. Rituximab has been frequently cited as an important adjunct therapy in desensitization protocols for highly sensitized transplant recipients as well as recipients of ABO incompatible transplants. Rituximab demonstrates promise in this regard and warrants additional consideration in prospective clinical trials.     

Immunology of transplantation

Understanding the interaction of foreign tissue with the recipient immune system is key to improving results from organ transplantation. Responses are mediated by the humoral and cellular arms of the host immune system towards the tissues of the transplant. Unchecked this can lead to rejection of the graft. Improvements in immunosuppressive therapy have countered these reactions to a degree but are not without side effects. Future work is directed at improving graft tolerance without unwanted host effects.