实验性变态反应性脑脊髓炎

实验性变态反应性脑脊髓炎是实验动物发生的一种变态反应性自身免疫病。本文综述了它的致脑炎抗原,致敏途径和方法,动物的选择和不同动物实验性变态反应性脑脊髓炎的区别、治疗,以及与人类脱髓鞘疾病的关系。     

实验性变态反应性脑脊髓炎模型研究进展

实验性变态反应性脑脊髓炎是人类多发性硬化的理想动物模型,在临床神经免疫学研究中具有重要意义。本文主要介绍了实验性变态反应性脑脊髓炎模型制备的有关问题,包括敏感动物品系、性别、年龄的选择,抗原的种类及选择,免疫方法,模型的制备及病情评分等。     

实验性变态反应性脑脊髓炎与脑屏障变化

脑屏障改变是实验性变态反应性脑脊髓炎 (EAE)较早期的病理改变 ,它促使免疫细胞及免疫信息分子大量入脑 ,从而引起脑组织的免疫炎性反应。本文对脑屏障概念 ,EAE时脑屏障变化情况及其可能的机理作一综述。     

实验性变态反应性脑脊髓炎的病理研究

目的　研究实验性变态反应性脑脊髓炎 (EAE)的病理变化。方法　利用光镜、电镜观察豚鼠 EAE模型的组织学改变。结果　光镜下可见脑实质及珠网膜下腔小血管充血 ,血管周围炎细胞浸润 ,呈“袖套”状改变 ,侧脑室旁白质及脊髓后联合、侧角出现髓鞘肿胀、崩解或消失。电镜下可见血管周围明显脱髓鞘 ,髓鞘呈松散状 ,部分区域斑块状脱落 ,明暗相间结构消失 ,轴突细胞器消失 ,神经元细胞尼 (氏 )小体消失 ,内质网扩张脱颗粒。结论　 EAE的病理改变主要为血管周围炎性浸润及白质脱髓鞘。     

实验性变态反应性脑脊髓炎相关细胞因子

实验性变态反应性脑脊髓炎(EAE)是一种以细胞免疫为主,以中枢神经系统白质损害为特征的自身兔疫病。在其发病机理及病情演化中,由细胞因子构成的免疫网络起着重要的调节作用,其中一类是由单核巨噬细胞及Th1细胞分泌的致炎细胞因子能够促使EAE的发生或加重病情,而由Th2细胞分泌的免疫抑制性细胞因子又可抑制或逆转EAE的病情。本文收集近年来对EAE相关细胞因子的研究进行综述,以求反映人类多发性硬化疾病的免疫病理。同时还对近来在细胞因子的检测方法及细胞因子在EAE模型的预防和治疗中作用的研究新进展进行了介绍。     

实验性变态反应性脑脊髓炎动物模型

此文介绍了实验性变态反应性脑脊髓炎动物模型制备的相关问题，包括敏感动物选择，抗原剂量，病情评分以及抗原特异性T细胞的培养，检测和被动转移模型。     

实验性变态反应性脑脊髓炎与细胞凋亡

实验性变态反应性脑脊髓炎 (EAE)是研究人类多发性硬化 (MS)的经典动物模型 ,EAE发病和愈复过程中细胞凋亡的情况也是目前神经生物学的研究热点。研究者们发现 ,EAE时CNS损伤区有自身反应性T淋巴细胞的凋亡 ,而且这种细胞凋亡促进了EAE的愈复和耐受状态的形成 ,这就为EAE乃至人类MS的防治提供了一条新思路。有关EAE其他细胞凋亡和影响细胞凋亡的因素也有一些研究。本综述对近年来这些方面的研究进展做了较为全面的回顾     

T淋巴细胞增殖在实验性变态反应性脑脊髓炎发病中的作用

目的　探讨T淋巴细胞增殖在实验性变态反应性脑脊髓炎 (EAE)发病中的作用。方法　观察Lewis大鼠主动EAE临床症状和T淋巴细胞增殖。结果　EAE临床发病过程中 ,T淋巴细胞增殖旺盛。结论　EAE时 ,活化的T淋巴细胞可以通过BBB进入CNS ,浸入CNS的淋巴细胞能产生破坏性的细胞因子TNF α及某些酶类 ,推测T淋巴细胞增殖活跃 ,在导致EAE发病过程中起着至关重要的作用。     

实验性变态反应性脑脊髓炎几种细胞因子的检测

目的和方法　为研究细胞因子在实验性变态反应性脑脊髓炎 (EAE)及多发性硬化 (MS)发病机制中的作用 ,用 CTL L细胞株滴定法检测了 EAE动物脾细胞培养上清中白细胞介素 - 2 (IL- 2 )的生物学活性 ,用EL ISA分别检测了白细胞介素 - 4 (IL - 4 )及干扰素 -γ(IFN-γ)水平。结果　 EAE组 IL - 2活性及 IFN-γ水平均显著高于正常对照组 (均为 P<0 .0 5) ,而其 IL- 4水平显著低于对照组 (P<0 .0 1)。结论　 IL- 2、IFN- γ等细胞因子参与了 EAE的发病 ,并对 IL- 4的产生有抑制作用。     

实验性变态反应性脑脊髓炎的启动过程

实验性变态反应性脑脊髓炎（EAE）发病机制十分复杂，实验证据表明EAE是自身免疫性CD4^＋ T细胞即Th1细胞激活后介导的一系列级联免疫反应。在疾病过程中大量细胞因子作用于特异的免疫细胞，或细胞因子之间相互作用，形成复杂免疫网络，并贯穿疾病的始终。至于细胞因子是如何作用于特异的免疫细胞，从而启动这一中枢免疫级联反应的，是国内外研究一直关注的焦点。本文就近2年这一领域的研究进展进行了总结和分析，进一步揭EAE的发病机制。     

Enhancing effects of irrelevant lymphocytes on adoptive transferred experimental allergic encephalomyelitis

To help understand effector mechanisms in experimental allergic encephalomyelitis (EAE) we examined the effects of adding ‘irrelevant’ lymphocytes from non-EAE donors to major basic protein (MBP)-reactive lymphocytes in the adoptive transfer of EAE (Tr-EAE). The intravenous injection of tentanus toxoid-reactive lymphocytes (TT-cells) and phytohemagglutinin-stimulated lymphocytes on the same day or 2 days after intra-arterial injection of MBP-reactive lymphocytes enhanced the clinical and pathological expression of Tr-EAE. In lymphocyte trafficking studies there was significant accumulation of these injected TT-cells in the central nervous system during enhanced transfer of EAE. W3/25-positive cells were much more predominant in lesion of central nervous system when reinjected with TT cells along with MBP cells compared with lesions of rats injected with MBP cells alone. These findings suggest possible participation of lymphocytes other than MBP-reactive cells in the expression of EAE and provide a useful model to further explore effector mechanism in the future.     

粘附分子在实验性变态反应性脑脊髓炎发生中的作用

目的 探讨粘附分子ＣＤ１１ａ,ＣＤ５４,ＣＤ６２在实验性变态反应性脑脊髓炎（ＥＡＥ）发生中的作用。方法 采用Ｗｉｓｔａｒ大鼠建立了ＥＡＥ动物模型,应用免疫荧光法检测下沉大鼠及ＥＡＥ动物周围血和脑组织中Ｔ细胞亚群及ＣＤ１１ａ,ＣＤ５４,ＣＤ６２的表达,结果 发病大鼠脑组织局灶周围大量淋巴细胞浸润,主要为ＣＤ４Ｔ细胞,发病大鼠周围血淋巴细胞上及大鼠脑组织粘附分子的表达明显升高,结论 粘附分子ＣＤ１１ａ     

新西兰兔和SD大鼠实验性变态反应性脑脊髓炎模型的比较

目的比较两种不同种属的动物及不同免疫原诱发的实验性变态反应性脑脊髓炎（EAE）模型的各自特点及其适用的优缺点。方法应用兔脊髓匀浆（R-SCH）、SD大鼠脊髓匀浆（M-SCH）、异种牛大脑白质匀浆（C-SCH）为免疫原，分别免疫新西兰兔和SD大鼠制备EAE动物模型。观察比较模型的发病过程、临床评分、病理变化和病理组织学评分。结果新西兰兔EAE模型呈单相发病过程，发病时间长，发病率较低，但其病灶大且集中，MRI更易观察和定位。SD大鼠EAE模型则呈典型的双相病程，发病时间短，发病率高，复发率高，其发病更像人类多发性硬化的发病过程。同时发现同种免疫原诱发的EAE模型其发病过程更稳定，发病率也较异种免疫原高．其导致的模型病理变化也更明显，尤其是脱髓鞘更明显。结论不同的动物物种和不同的免疫原制备的EAE模型具有各自适用的优缺点和特点，可根据研究目的的不同选取所需的模型。     

Sympathectomy augments adoptively transferred experimental allergic encephalomyelitis

Adoptively transferred experimental allergic encephalomyelitis (EAE) was significantly augmented in Lewis rats with ablated sympathetic nervous system. Sympathectomy was obtained by treatment of newborn rats with 6-hydroxydopamine. Sham-injected rats were used as a control. EAE was elicited in 7-8-week-old donor Lewis rats by immunization with a suspension of guinea pig (GP) brain and spinal cord in complete Freund's adjuvant. Successful transfer of EAE was accomplished with 50 x 10(6) lymph node cells (LNC)/rat, incubated for 72 h with GP myelin basic protein. LNC were obtained from draining lymph nodes, 9 days after immunization for EAE. The severity of passively transferred EAE was significantly augmented when donor LNC obtained from normal Lewis rats immunized for EAE were injected into sympathectomized rats as compared to sham-injected rats. When LNC were obtained from sympathectomized or sham-injected donors, the disease was significantly more severe in recipients of cells from sympathectomized animals. The severity of histological lesions in the brain and spinal cord was greater in rats with passively transferred EAE which received LNC from sympathectomized donors.     

Studies of experimental allergic encephalomyelitis in old mice

In old BALB/c mice susceptibility to experimental allergic encephalomyelitis (EAE) with bovine proteolipid apoprotein (PLP) is reduced significantly. Eleven of 21 8-week BALB/c mice developed clinical signs of EAE following injection of PLP but only two of 18 12-month BALB/c mice and one of 19 24-month BALB/c mice showed clinical signs of EAE. Susceptibility to EAE induced by either PLP or bovine myelin basic protein (MBP) also was reduced in old SJL mice. However, the aging process had no effect on the clinical signs of EAE in both strains, if EAE appeared. Some old BALB/c mice developed histologic EAE with significant demyelination without clinical signs. Lymphocyte proliferative response to mitogens and antigens, and interleukin-2 (IL-2) production, also were depressed in the aged mice (24-month BALB/c and 18-month SJL) probably due to the functional defect of T cells, since the function of macrophages as antigen-presenting cells was not affected in the old mice. PLP-sensitized spleen cells (SPC) from 8-week mice were able to adoptively transfer EAE to young and aged recipients. PLP-sensitized T cells from 8-week mice, reconstituted with young or old monocytes, also were able to transfer EAE into young mice. In contrast, spleen cells from aged mice did not induce EAE, so the reduction of EAE susceptibility was mainly explained by the failure of T cell activity. This T cell defect was not restored by exogenous IL-2.     

Characteristics of the T lymphocytes involved in experimental allergic encephalomyelitis

Both heterogeneity and restricted heterogeneity of the encephalitogenic myelin basic protein (MBP) peptide-specific T cell receptors (TCRs) were demonstrated in inbred animals depending on the strain-specific genetic characteristics, the stage of the disease, the compartment of the lymphocytes obtained and the methodology used. Nevertheless, the similar features of some MBP-specific TCRs demonstrated across species suggest that conservation of these autoantigen-specific molecules undoubtedly exists, even though the degree of this conservation is controversial. However, the unequivocal heterogeneity of the immune response directed at one of the most important myelin constituents, proteolipid lipoprotein (PLP), which occurs either as a primary or a secondary event during experimental allergic encephalomyelitis (EAE), indicates the complexity of the in vivo situation. Intramolecular and intermolecular spreading of antigen specificity during the course of the disease indicates that a TCR directed therapy may not be the choice of intervention in established disease even in individual strains of laboratory animals with restricted heterogeneity of the primary MBP-specific response. Studying the sequence of events, the recruited regulatory cells and cytokines, and the stromal factors controlling persistence or death of activated, memory cells in the tissue lesion, may reveal new therapeutic modalities with more universal applicabilities.     

实验性变应性猴脑脊髓炎的超微结构改变

目的探讨自身免疫性中枢神经系统（ＣＮＳ）脱髓鞘的病理特点和发病过程。方法建立猴实验性变态反应性脑脊髓炎（ＥＡＥ）的模型，并从病情不同阶段进行病理取材和电镜观察。结果（１）ＥＡＥ脱髓鞘最早的靶是少突胶质细胞（ＯＤＣ），而不是髓鞘本身；（２）无论急性期还是慢性期，脱髓鞘病灶内只有极少的炎细胞浸入；（３）急性期髓鞘改变轻微，以变性为主，ＯＤＣ肿胀显著，轴突相对完整。远离髓鞘变性区有大量炎细胞浸入；（４）慢性期病变区髓鞘脱失明显，ＯＤＣ严重变性或部分丢失，继发性轴突变性，边缘可见少量薄的髓鞘再生，血脑屏障破坏。结论ＥＡＥ的ＣＮＳ脱髓鞘过程首先累及ＯＤＣ。     

Blood levels of kinins in experimental allergic encephalomyelitis

The pathology of acute experimental allergic encephalomyelitis is characterized by perivascular cellular infiltrates in the central nervous system. Our hypothesis is that this immuno-pharmacological process can activate the circulating and tissular kallikrein-kinin systems. We studied 21 New Zealand rabbits inoculated with a homogenate of guinea-pig spinal cord in complete Freund's adjuvant. Each animal underwent radioimmunoassay for arterial blood bradykinin, des-Arg9-bradykinin and des-Phe8-des-Arg9-bradykinin during the acute or subacute clinical phase of encephalomyelitis. Immediately after blood sampling, all animals had their complete central nervous system dissected out and prepared for staining and histological study. The number of hematoxylin-eosin-stained perivascular cellular infiltrates was counted at eight levels of the central nervous system, from the hypothalamic to sacral spinal segments. We demonstrated a positive significant (P less than or equal to 0.02) correlation (r = 0.55) between the number of perivascular cellular infiltrates and blood level of the biologically active kinin bradykinin.     

About demyelinating properties of humoral antibodies in experimental allergic encephalomyelitis

Summary In order to elucidate the role of humoral antibodies in the pathogenesis of myelin lesions in experimental allergic encephalomyelitis (EAE) a combined in vivo and in vitro study was done using rabbits immunized with the purified A₁ basic protein. Rabbits injected with whole white matter were used for comparison. Demyelinating activity appeared in the rabbit sera 5 days after injection, as tested in myelinated organotypic tissue cultures. In spite of this no lesions of the myelin preceded the appearance of inflammatory cells in the living animals. In the spinal cord changes in vascular permeability, as revealed by leakage of Evans blue-albumin complex, appeared at the same times as the cells. In contrast to in vitro, the mere presence of circulating antibodies in vivo does not appear to be enough to cause structural changes of the myelin. Possible reasons for this discrepancy are discussed; it is emphasized that the inflammatory changes develope first in areas where the so-called blood-brain barrier to diffusion of proteins is lacking.     

实验性变态反应性脑脊髓炎大鼠星形胶质细胞的变化

目的观察实验性变态反应性脑脊髓炎(EAE)大鼠脊髓中星形胶质细胞的变化,探讨EAE大鼠的发病相关生物学机制。方法采用免疫组化法,对豚鼠全脊髓匀浆诱导的Wistar大鼠EAE的过程中,脊髓内星形胶质细胞变化情况进行研究。结果EAE大鼠症状高峰期时星形胶质细胞开始激活,恢复期时激活达到高峰,而且活化的星形胶质细胞未见表达主要组织相容性抗原(MHC)。结论活化的星形胶质细胞可能与EAE大鼠的恢复有关。