人化SCID鼠的建立及其对脊髓灰质炎病毒的免疫应答

经测定鼠尾采血获取的血清,10只SCID鼠在所设实验室条件下饲养4个月前后均达到鼠IgG含量低于5μg/ml的合格标准,5只SCID鼠腹腔移植入2或4×10~7个人外周血淋巴细胞(hu—PBL),建立人化SCID(hu-PBLSCID)鼠,可在移植后4周和12周测到其血清中人IgG的存在,最高可达109μg/ml。以脊髓灰质炎Ⅰ型病毒(Polio—1 virus,Polio-1)作抗原免疫5只hu-PBL-SCID各5次,每鼠均能产生抗Polio-1的特异性人抗体,滴度最高达1:640,表明所建立的人化SCID鼠具备了一定的免疫应答能力。     

淋巴细胞免疫应答异常

淋巴细胞免疫应答异常吴厚生（上海医科大学免疫教研室，上海２０００３２）Ａｂｓｔｒａｃｔ：Ａｂｎｏｒｍａｌｉｔｙｏｆｉｍｍｕｎｅｒｅｓｐｏｎｓｅｃａｎｂｅｄｅｖｉｄｅｄｉｎｔｏｔｗｏｇｒｏｕｐｓｗｉｔｈｅｉｔｈｅｒｓｐｅｃｉｆｉｃｉｔｙｏｒｎｏｎ－ｓｐ...     

Hu—TLC—SCID小鼠的建立及其对2型登革病毒的免疫应答

利用２型登革病毒（ＤＶ２）体外免疫人扁桃腺淋巴细胞（Ｈｕ－ＴＬＣ）移植给ＳＣＩＤ小鼠，以建立Ｈｕ－ＴＬＣ－ＳＣＩＤ小鼠。并用不同剂量灭活ＤＶ２加强免疫，观察小鼠对ＤＶ２的免疫应答。结果表明，移植Ｈｕ－ＴＬＣ后第２周起，可在Ｈｕ－ＴＬＣ－ＳＣＩＤ小鼠血清中检出入ＩｇＧ，最高达４１２．８６μｇ／ｍｌ。移植后次日用不同剂量灭活ＤＶ２加强免疫，每２周加强１次，首次加强免疫后第２周，Ｈｕ－ＴＬＣ－ＳＣＩＤ小鼠血清中出现抗ＤＶ２特异性人ＩｇＭ；第４周起有特异性人ＩｇＧ产生，最高达１：６４００。其含量和产生动态与抗原量有关。     

重建SCID小鼠免疫功能对肝癌抗原的体液免疫应答

为在ＳＣＩＤ小鼠体内获得人免疫Ｂ淋巴细胞，将１２～１４周龄的胎儿肝细胞（１～２）×１０１０／Ｌ腹腔注射于ＳＣＩＤ小鼠，然后再分次接种肝癌细胞。用ＥＬＩＳＡ法于第４，５，６周连续检测ＳＣＩＤ－ｈｕ小鼠血清人ＩｇＧ；用免疫组化ＡＢＣ法检测各种组织中的人淋巴细胞。各实验小鼠均检测到人ＩｇＧ的存在，最高为３９１μｇ／Ｌ，且随时间的延长呈上升趋势。在ＳＣＩＤ－ｈｕ小鼠肝、脾及腹腔接种瘤组织的周边，可见人ＣＤ３＋和ＣＤ２０＋的淋巴细胞。上述结果表明，用人胎肝细胞移植可在ＳＣＩＤ小鼠体内获得人淋巴细胞，并对人肝癌细胞抗原产生免疫应答，分泌一定水平的抗人肝癌的抗体。提示：用人胎肝细胞在ＳＣＩＤ小鼠体内可建立人免疫系统的部分功能。     

鼻相关淋巴组织及其免疫应答

鼻相关淋巴组织（ＮＡＬＴ）是鼻粘膜中主要的免疫防御屏障。近年来鼻内免疫已成为继口服免疫之后诱导粘膜免疫力的又一有效途径。本文就鼻粘膜部位诱导的免疫应答研究进展作一简要综述。     

过敏性哮喘的免疫应答

本文着重介绍了过敏原进入下呼吸道后的局部免疫应答，主要涉及肺泡巨噬细胞数量和递呈抗原活性的增强；Ｔ淋巴细胞的活化和释放多种细胞因子（ＩＨ－４、ＩＨ－５等）；Ｂ淋巴细胞经二种信号作用克隆增殖，分泌较多的ＩｇＥ或ＩｇＧ４；肥大细胞、嗜酸粒细胞数量增加并释放多种递质及免疫应答的定位。     

未成熟树突细胞诱导同种免疫低应答性的研究

目的：证实缺少辅助刺激分子的未成熟树突细胞（ＤＣ）在体外诱导同种Ｔ细胞的低应答性。方法：应用骨髓微血管内皮细胞作为饲养细胞扩增同品系小鼠骨髓细胞,经不同浓度ＧＭ－ＣＳＦ作用,在体外培养出不同发育阶段的ＤＣ。采用初次和再次单向混合淋巴细胞培养方法观察Ｂａｌｂ／ｃ小鼠脾脏Ｔ细胞对同种未成熟ＤＣ或脾细胞的应答能力。结果：在初次ＭＬＲ试验中,Ｂａｌｂ／ｃ Ｔ细胞对Ｃ５７ＢＬ／６小鼠未成熟ＤＣ刺激只呈现出微     

甲型肝炎减毒活疫苗免疫小鼠后的体液和细胞免疫应答

减毒活疫苗进入体内在增殖的过程中，可以刺激T淋巴细胞分化，产生细胞免疫；使用甲型肝炎减毒活疫苗后发现，诱发的抗体阳转率往往低于疫苗保护率，推测疫苗引起的抗体应答是疫苗保护机制的一部分，而另外重要的一部分应该是细胞免疫。本研究拟在检测抗体反应的同时，观察疫苗免疫后T淋巴细胞免疫应答，探讨接种甲型肝炎减毒活疫苗后产生免疫保护的机制。     

非特异免疫对特异性免疫应答的指导作用——抗原选择与应答类型

本文介绍一个新的概念：非特异免疫系统的细胞和体液成份可为特异性免疫提供指导,决定特异性免疫对抗原的选择性并左右其应答类型。     

结核菌H37Ra在小鼠体内诱导的免疫应答及其保护力

目的:研究结核菌H37Ra免疫小鼠后产生的特异性免疫应答以及保护效果.方法:BALB/c小鼠随机分为H37Ra组、BCG组和生理盐水(NS)组,免疫8周后处死部分小鼠,取脾淋巴细胞经体外培养、PPD刺激后,MTT法检测淋巴细胞的刺激指数,ELISA法检测培养上清液中IFN-γ和IL-4水平.另一部分免疫小鼠经腹腔感染结核分枝杆菌(Mycobacterium tuberculosis,MTB)毒株H37Rv,4周后处死,测定小鼠脏器重量指数.取稀释的小鼠脾脏和肺脏匀浆接种于改良罗氏培养基,培养21天后计数脏器荷菌量.结果:H37Ra和BCG免疫小鼠脾淋巴细胞刺激指数、IFN-γ和IL-4水平均显著高于NS对照组.感染4周后H37Ra和BCG组小鼠脏器重量指数较NS对照组均显著降低.H37Ra组小鼠脾脏和肺脏荷菌量与NS对照组比较分别下降了1.228log10CFU和0.954log10CFU,差异有显著性(P<0.05),与BCG组之间差异均无显著性.结论:H37Ra免疫小鼠后可以诱导产生Th1型免疫应答,能够抵抗毒株H37Rv的攻击,且免疫效果与BCG相当.     

Erythropoietin enhances immune responses in mice

Erythropoietin (Epo) is the main erythropoietic hormone. Recombinant human Epo (rHuEpo) is thus used in clinical practice for the treatment of anemia. Accumulating data reveals that Epo exerts pleiotropic activities. We have previously shown an anti-neoplastic activity of Epo in murine multiple myeloma (MM) models, and in MM patients. Our findings that this anti-neoplastic effect operates via CD8+ T lymphocytes led us to hypothesize that Epo possesses a wider range of immunomodulatory functions. Here we demonstrate the effect of Epo on B lymphocyte responses, focusing on three experimental models: (i) tumor-bearing mice, (5T2 MM mouse); (ii) antigen-injected healthy mice; and (iii) antigen-injected transgenic mice (tg6), overexpressing human Epo. In the MM model, despite bone marrow dysfunction, Epo-treated mice retained higher levels of endogenous polyclonal immunoglobulins, compared to their untreated controls. In both Epo-treated wild type and tg6 mice, Epo effect was manifested in the higher levels of splenocyte proliferative response induced in vitro by lipopolysaccharide. Furthermore, these mice had increased in vivo production of anti-dinitrophenyl (DNP) antibodies following immunization with DNP-keyhole limpet hemocyanin. Epo-treated mice showed an enhanced immune response also to the clinically relevant hepatitis B surface antigen. These findings suggest a potential novel use of rHuEpo as an immunomodulator.     

Comparison of immune responses against foot-and-mouth disease virus induced by fusion proteins using the swine IgG heavy chain constant region or beta-galactosidase as a carrier of immunogenic epitopes

Previously, we demonstrated that a fusion protein (Gal-FMDV) consisting of beta-galactosidase and an immunogenic peptide, amino acids (141-160)-(21-40)-(141-160), of foot-and-mouth disease virus (FMDV) VP1 protein induced protective immune responses in guinea pigs and swine. We now designed a new potential recombinant protein vaccine against FMDV in swine. The immunogenic peptide, amino acids (141-160)-(21-40)-(141-160) from the VP1 protein of serotype O FMDV, was fused to the carboxy terminus of a swine immunoglobulin G single heavy chain constant region and expressed in Escherichia coli. The expressed fusion protein (IgG-FMDV) was purified and emulsified with oil adjuvant. Vaccination twice at an interval of 3 weeks with the emulsified IgG-FMDV fusion protein induced an FMDV-specific spleen proliferative T-cell response in guinea pigs and elicited high levels of neutralizing antibody in guinea pigs and swine. All of the immunized animals were efficiently protected against FMDV challenge. There was no significant difference between IgG-FMDV and Gal-FMDV in eliciting immunity after vaccination twice in swine. However, when evaluating the efficacy of a single inoculation of the fusion proteins, we found that IgG-FMDV could elicit a protective immune response in swine, while Gal-FMDV only elicited a weak neutralizing activity and could not protect the swine against FMDV challenge. Our results suggest that the IgG-FMDV fusion protein is a promising vaccine candidate for FMD in swine.     

Osthole promotes anti-tumor immune responses in tumor-bearing mice with hepatocellular carcinoma

Abstract

Osthole, a natural coumarin derivative, has been shown to have anti-tumor and anti-inflammatory activity. However, the effect of osthole on anti-tumor immune responses in tumor-bearing mice has not yet been reported. In the present study, osthole treatment did not affect the weight and the coefficient of thymus and spleen in tumor-bearing mice with hepatocellular carcinoma (HCC). However, osthole administration significantly elevated the proportion and number of the splenic CD8⁺ T cells, the proportion of CD4⁺ T and CD8⁺ T cells in tumor tissues, and the levels of IL-2 and TNF-α in the serum of HCC tumor-bearing mice. Our results suggested that osthole could promote the activation of the tumor-infiltrating CD4⁺ T and CD8⁺ T cells, and elevate the proportion of CD4⁺ and CD8⁺ effector T cells. Osthole treatment also significantly decreased the proportion of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in the spleen. Taken together, osthole could enhance the T cell mediated anti-tumor immune responses in the tumor-bearing mice with HCC.     

Lymphocyte populations and immune responses in CD5-deficient mice

The CD5 antigen is expressed at a high level on T cells from early on in thymocyte ontogeny and continues to be expressed on the surface of all mature T cells. In addition, it marks a population of B lymphocytes (B-1a) with distinct physiological properties. To study the in vivo function of CD5, the murine gene was inactivated using the technique of homologous recombination in embryonic stem cells. In homozygous mutant mice the CD5 antigen is not expressed on the surface of either T or B lineage cells, indicating that in both cell populations this antigen is encoded by the same gene. CD5-deficient (CD5T) mice are healthy and populations of T and B lymphocytes in these mice look unchanged when compared to control mice. The mutant mice are able to mount effective immune responses to T cell-dependent and -independent antigens.     

rIL-18对肺炎链球菌肺炎小鼠Th1/Th2免疫应答的影响

目的 研究重组白细胞介素18(rIL-18)对肺炎链球菌肺炎小鼠Th1/ Th2免疫应答的影响.方法 鼻腔接种肺炎链球菌建立小鼠肺炎链球菌肺炎模型,将Balb/c小鼠24只随机分为3组,分别为对照组,肺炎组和肺炎rIL-18干预组(n=8 ),RT-PCR法检测各组小鼠肺组织中IFN-γ、IL-4 mRNA 的表达,同时支气管肺泡灌洗液(BALB)进行活菌计数,有核细胞分类计数.结果 ①肺炎rIL-18干预组BA LF中性粒细胞和巨噬细胞计数显著高于肺炎组和对照组(P＜0.001);②肺炎rIL-18 干预组BALF活菌计数显著低于肺炎组(P＜0.001);③肺炎rIL-18干预组肺组织IFN- γ mRNA表达上调而IL-4 mRNA表达下调(P＜0.001).结论 在小鼠肺炎链球菌肺炎早期给予rIL-18可诱导IFN-γ的合成,促进Th1免疫应答,使Th1/ Th2免疫平衡向Th1免疫偏移、促进宿主对肺炎链球菌的防御.     

Role of natural and immune IgM antibodies in immune responses

IgM antibodies constitute the major component of the natural antibodies and is also the first class of antibodies produced during a primary antibody response. The IgM-type antibodies differ from other classes of antibodies in that they are predominantly produced by B1 cells, in the absence of apparent stimulation by specific antigens. In addition, IgM antibodies are mostly encoded by germline V gene segments and have low affinities but broad specificites to both foreign and self structures. New developments regarding the function of both immune IgM antibodies and natural IgM antibodies will be examined here.     

Social neuroscience: Autonomic, neuroendocrine, and immune responses to stress

The immune system is influenced by central nervous system processes that are shaped by social and psychological factors. Considerations of social factors, intrapersonal processes, and autonomic psychophysiology therefore may contribute to a fuller understanding of both immune and brain function. Research reviewed here (a) examines the socioemotional factors that contribute to, or moderate, responses to brief and chronic stressors, (b) determines whether or not stable individual differences in heart rate reactivity predict neuroendocrine and immune responses to a brief psychological stressor and to an influenza virus vaccine, and (c) investigates the autonomic origins of individual differences in low and high heart rate reactivity and their relationship to neuroendocrine and immune responses to chronic and acute stressors. Among our findings are: (a) acute psychological stressors activate the sympathetic adrenomedullary system across individuals and affect immune function; and (b) individuals characterized by high sympathetic cardiac reactivity to acute psychological stressors also show a relative activation of the hypothalamic pituitary adrenocortical system and altered immune function.     

Mast cell-mediated immune responses through IgE antibody and Toll-like receptor 4 by malarial peroxiredoxin

In this study, 2-Cys Plasmodium berghei ANKA (PbA) peroxiredoxin (Prx) was identified as an antigenic protein recognized by an anti-PbA IgE antibody using two-dimensional polyacrylamide gel electrophoresis and proteomic analysis. Innate immune responses to PbAPrx were examined using cells from mice deficient in Toll-like receptors (TLR) or related molecules, and it was demonstrated that responses were severely impaired in TLR4(-/-), MyD88(-/-) and MD-2(-/-) mice, but not in Toll/IL-1 receptor domain-containing adaptor inducing IFN-gamma (TRIF)(-/-), TLR2(-/-) or radioprotective 105 (RP105)(-/-) mice. An association between PbAPrx and TLR4 was observed following immunoprecipitation and immunoblotting, suggesting that PbAPrx was associated with TLR4/MD-2. Interactions between Prx and TLR4/MD-2 were also examined by flow cytometry using TLR4/MD-2- or TLR2-expressing cells. NFkappaB/GFP activity was observed in TLR4/MD-2- but not in TLR2-expressing cells following stimulation with Prx. However, this effect was not observed after treatment with proteinase K, suggesting that PbAPrx is a protein ligand for TLR4 and that the PbAPrx activity observed in this study is not due to contamination with LPS. These findings indicate that malarial Prx induces IgE-mediated protection through FcepsilonRI on mast cells and innate immunity through TLR4 with MyD88 and MD-2, suggesting a novel function for malarial Prx in innate and acquired immune responses in malaria.     

视黄酸及其受体在机体免疫中的作用

视黄酸(retinoic acid,RA)又名维甲酸是维生素A的活性衍生物,是小分子质量、脂溶性信号分子,通过与其细胞内的受体α(retinoic acid receptorα,RARα)结合发挥生物学功能,在调节生物各种进程如细胞分化、调亡、胚胎发育、再生和视力发育中发挥重要作用。研究表明在很多疾病如炎症性肠病(IBD)、肿瘤等患者体内视黄酸含量减少,给予视黄酸制剂能有效的抑制疾病的进程。目前视黄酸在机体免疫调节中发挥的作用尚不完全明确,有人认为其通过对Th1/Th2和Th17/Treg平衡的调节而发挥在机体抑制炎症的作用,而在肿瘤方面的作用机制则较为复杂。本文将对视黄酸在机体免疫中发挥的作用做一综述。