C1q对树突状细胞的免疫调节作用

树突状细胞是机体最强的抗原提呈细胞,调控着机体的免疫应答和耐受。补体分子C1q作为补体C1的组分,在补体经典途径的活化中发挥着重要作用。近年来研究显示,C1q能够影响树突状细胞的免疫功能,参与免疫应答的调控。     

Rac1的免疫调节作用及其与疾病的关系

Rho蛋白是一种具有三磷酸鸟苷(GTP)酶活性的小分子蛋白,Rac1是其家族成员之一,是细胞内重要的信号转导分子,在多种细胞的基本功能中发挥分子开关作用.它一方面可参与免疫调节及细胞周期、细胞骨架重排、细胞运动与转移的调节等,另一方面在许多疾病如哮喘、房颤、感染性疾病、肿瘤等中异常表达,且与肿瘤的侵袭和转移密切相关,有可能成为判断肿瘤发展和预后的新指标.     

胰岛素样在子1的免疫调节作用的体外实验研究

目的：探讨胰岛素生长因子１的免疫调节作用。方法：随机抽取健康个体８２名和肿瘤个体１２６名,体外撮以外周血淋巴细胞后钭ＩＬ－２和或／ＩＧＦ－１共同培养,用＆＾３Ｈ－ＴｄＲ掺入法,＾３Ｈ－ＴｄＲ释放法及流式细胞仪检测淋巴细胞增殖活性,杀伤活性和ＣＤ４＾＋／ＣＤ＾８＋比率。     

胰岛素样生长因子1的免疫调节作用的体外实验研究

目的：探讨胰岛素样生长因子１（ＩＧＦ１） 的免疫调节作用。方法：随机抽取健康个体８２ 名和肿瘤个体１２６ 名,体外提取外周血淋巴细胞后将ＩＬ２ 和或ＩＧＦ１ 共同培养,用３ ＨＴｄＲ 掺入法、３ ＨＴｄＲ 释放法及流式细胞仪检测淋巴细胞增殖活性、杀伤活性和ＣＤ４＋ ＣＤ８＋ 比率。结果：适当浓度的ＩＧＦ１（５０ ｎｇｍｌ）在体外能协同ＩＬ２ 促进ＬＡＫ细胞的增殖,增强其杀伤Ｒａｊｉ细胞的活性,提高淋巴细胞亚群ＣＤ４＋ ＣＤ８＋ 的比率。结论：ＩＧＦ１ 在体外对人体外周血免疫细胞起正向调节作用。     

抗小鼠TLR2胞外段单表位抗体TSP-2对OVA诱导的小鼠过敏性哮喘气道炎症的影响

目的观察抗小鼠TLR2胞外段单表位（mTLR2ECD）抗体（TSP-2）对OVA诱导的小鼠过敏性哮喘气道炎症的影响。方法用肺泡灌洗、组织切片及特异染色、免疫组化、ELISA法检测TSP-2对小鼠哮喘模型的气道炎症和炎症细胞的浸润以及肺组织中肺泡及支气管结构的影响。结果发现静脉给予抗体TSP-2能有效抑制气道炎症和炎症细胞的浸润。主要表现在肺泡灌洗液中的白细胞浸润减少、减轻血清中OVA特异性IgE抗体的降低以及抑制OVA诱导的小鼠肺泡毛细血管充血水肿等病理变化。结论抗体TSP-2对过敏性哮喘的病理变化有一定的抑制作用。     

白芍总甙对佐剂性关节炎大鼠的免疫调节作用及其与一氧化氮关系的研究

通过检测脾细胞增殖反应、不同细胞培养上清中亚硝酸盐含量以及采用一氧化氮（ＮＯ）合成酶抑制剂等工具药研究了白芍总甙（ＴＧＰ）对佐剂性关节炎（ＡＡ）大鼠免疫调节作用及其与ＮＯ的关系。结果表明，ＡＡ大鼠脾细胞低下的刀豆蛋白Ａ（ＣｏｎＡ）增殖反应与其巨噬细胞（Ｍ）过量产生ＮＯ有关；ＴＧＰ５０ｍｇ／（ｋｇ·ｄ）治疗７ｄ上调ＡＡ大鼠细胞低下ＣｏｎＡ反应是其下调Ｍ产生ＮＯ等抑制性介质的结果。结果还表明，ＴＧＰ可使ＡＡ大鼠腹腔Ｍ升高的ＮＯ和肿瘤坏死因子产生降低或恢复。     

普通小麦对OVA诱导小鼠过敏反应的抑制作用及机制北大核心CSCD

目的 旨在探讨普通小麦（TA）对卵清蛋白（OVA）致敏小鼠过敏反应的作用及其机制.方法 将25只BALB/c雌鼠随机分为对照组、OVA组、TA 100 mg/kg组、TA 200 mg/kg组和地塞米松（dexamethasone,DEX）组,每组5只.将OVA 20μg与氢氧化铝1 mg溶解于100μl PBS溶液中,并向每只实验组小鼠腹腔内注射以致敏小鼠,而对照组小鼠腹腔内则注射100μl 0.9％生理盐水,饮用水饲养.首次致敏后2周,重复上述操作,并将不同浓度药物稀释于1％CMC溶液中继续饲养,饲养过程中记录每只小鼠的过敏症状与行为评分.首次致敏后12 d对照组、实验组小鼠外耳皮下分别注射20μl 0.9％生理盐水与OVA溶液,6 h、24 h测量每只小鼠外耳厚度,24 h后剪取各组小鼠外耳组织经苏木精-伊红（HE）染色后观察过敏症状.首次致敏后6周,颈椎脱臼法处死小鼠,经腹主动脉采集的血液经离心、取上清后,通过ELISA试剂盒检测IgE、IgG1、TNF-α、IL-4及抗OVA IgE、IgG1了解各炎性细胞因子的分泌情况;取出的脾脏组织提取其淋巴细胞后接种于培养皿,以不同的药物刺激后利用ELISA检测Th1细胞因子（IFN-γ、IL-12）及Th2细胞因子（IL-4、IL-5、IL-13）,利用RT-PCR检测脾淋巴细胞中IFN-γ、IL-4、IL-5、IL-12及IL-13的表达情况.结果 OVA组小鼠的过敏症状行为评分与外耳厚度均显著高于对照组及其他实验组,差异有统计学意义（P〈0.05）,实验组中其与TA呈剂量依赖性降低,组织病理学结果也证实了上述结果.ELISA结果显示,实验组小鼠血浆中IgE、IgG1、IL-4及TNF-α水平与对照组比较显著升高,其水平与TA呈剂量依赖性降低,尤其是IgE、TNF-α在TA高浓度组显示出与DEX组相似的抑制效果.RT-PCR结果显示,实验组较对照组Th1细胞因子（IFN-γ、IL-12）的含量显著增加,差异有统计学意义（P〈0.05）,其水平与TA未显示出剂量依赖性效应,而DEX组显示出明显的抑制作用.实验组Th2细胞因子（IL-4、IL-5及IL-13）的表达显著高于对照组,差异有统计学意义（P〈0.05）,TA组的IL-4、IL-5、IL-13表达均较OVA组有不同程度的降低,尤其在TA 100μg/ml组中其表达较OVA组分别降低了约60％、18％与20％,显示出了明显的抑制作用.结论 TA可能通过选择性抑制Th2细胞因子（IL-4、IL-5、IL-13）及IgE、IgG,而未抑制Th1细胞因子（IFN-γ、IL-12）,在保持体内免疫平衡的基础上有效降低过敏相关免疫应答,从而发挥抗过敏作用.本研究为新型抗过敏治疗药物（TA）的开发提供理论基础和实验依据.     

抗鼠IL－1α、IL－6单抗对狼疮倾向NZB／W F1小鼠的免疫调节研究

对狼疮倾向ＮＺＢ／ＷＦ１小鼠在４月龄时腹腔注射抗鼠ＩＬ－１α、抗ＩＬ－６单抗，每日１次１０μｇ×３ｄ，后每月１次×３次，１１月龄活杀，发现这样的剂量不能完全防治狼疮性肾炎，但可减轻蛋白尿，明显降低血清ＩＬ－１α水平，抑制腹腔巨噬细胞分泌ＩＬ－１α。对ＩＬ－６和ＴＮＦ－α水平无明显影响。     

Clq／ClqR系统免疫调节作用及其跨膜信号转导机制的研究（摘要）

Ｃｌｑ／ＣｌｑＲ系统免疫调节作用及其跨膜信号转导机制的研究（摘要）陈政良，谢佩蓉Ｃｌｑ／ＣｌｑＲ系统是一个新领域，许多方面的研究亟待开拓和深入。本文采用ＥＬＩＳＡ、ＦＡＣＳ、ＲＢＡ及ＷＢ等方法，证实了人Ｔ细胞系Ｊｕｒｋａｔ、Ｂ细胞系Ｒａｊｉ和系Ｕ９３...     

Adjuvant effect of zinc oxide on Th2 but not Th1 immune responses in mice

Background and aim: We investigated the effect of zinc oxide (ZnO) on Th1 and Th2 immune responses in mice.

Material and methods: Mice were intraperitoneally administered with ovalbumin (OVA) with or without varying doses of ZnO (day 0). On day 21, anti-OVA IgG, IgG2a, IgG1, and IgE antibodies in sera, OVA-specific proliferative responses of spleen cells, and production of Th1 cytokines including IFN-γ as well as Th2 cytokines such as IL-4 and IL-5 were measured.

Results: The results showed that administration of OVA with ZnO was followed by greater increases in anti-OVA IgG and the antigen-specific splenocyte proliferation compared to that of OVA alone. The production of anti-OVA IgG1 and IgE and secretion of IL-4 and IL-5 were markedly enhanced by ZnO. The enhancing effect of ZnO on these Th2 responses was as strong as aluminium hydroxide (Alum) that was widely used as an adjuvant. In contrast, treatment with OVA plus ZnO failed to affect production of anti-OVA IgG2a as well as IFN-γ. It was also observed that ZnO had a stimulating effect on the secretion of the proinflammatory cytokine IL-17 from a new lineage of effector Th cells.

Conclusion: These results suggest that ZnO appears to have an adjuvant effect on the immune system, especially Th2 but not Th1 immune responses.     

双歧杆菌完整肽聚糖对重组乙肝表面抗原的佐剂效应

目的 探讨双歧杆菌完整肽聚糖对重组乙肝表面抗原的吸附作用及其佐剂效应。方法 从双歧杆菌细胞壁提取完整肽聚糖，以不同方式与重组乙肝表面抗原结合，检测其对重组乙肝表面抗原的吸附作用；制备免疫原接种BALB／c小鼠，观察小鼠免疫后状态和生长情况，检测小鼠血清特异性抗体应答情况的变化。结果 在磷酸盐缓冲液中，完整肽聚糖对重组乙肝表面抗原的吸附呈剂量依赖性，作为佐剂免疫小鼠后无毒副反应出现，小鼠血清抗体阳性率和抗体滴度明显提高，IgC2a/IgG1增大。结论 双歧杆菌完整肽聚糖能够吸附重组乙肝表面抗原，增强机体相应的体液免疫应答和细胞免疫应答，具备良好的免疫佐剂效应。     

Evaluation of the LTK63 adjuvant effect on cellular immune responses to measles virus nucleoprotein

Background

A lot of pathogens enter the body via the nasal route. The construction of non-toxic mutants of heat labile Escherichia coli enterotoxin (LT), which is a potent mucosal adjuvant, represents a major breakthrough for the development of mucosal vaccines.

Objective

This study was undertaken to critically evaluate the adjuvanticity of the mutant of LT (LTK63) on the cellular immune responses to intranasally co-administered recombinant measles virus nucleoprotein (rMVNP).

Methods

Groups of CBA mice were immunized intranasally with rMVNP with or without LT or LTK63 as adjuvants. Another group was immunized subcutaneously with rMVNP in Freund''s adjuvant. rMVNP and measles virus (MV) were used in a proliferation assay to test the LTK63 potentiating ability to induce T cell responses. Subsequently MVNP synthetic peptides spanning the length of the N protein were used with a proliferation assay to identify the T cell epitopes.

Results

Splenocytes from mice immunized intranasally with rMVNP plus LT or LTK63, showed strong dose dependent proliferative responses to both the MVNP and MV. However, proliferative responses from the latter group were significantly lower than the former group (P < 0.05). Splenocytes tested recognized peptides 20, 21, 28, 31, 39, 40 and 50, suggesting these to be among important epitopes. Subcutaneous route was not effective in priming for T cell responses to rMVNP.

Conclusion

These data further demonstrate the great potential of LTK63 as a safe mucosal vaccine adjuvant.     

纳曲酮临床应用及其免疫调节机制研究进展

纳曲酮是一种阿片受体拮抗剂,对免疫系统具有调节作用.早期纳曲酮被用来治疗阿片类药物依赖,最近用来治疗肥胖、瘙痒、多发性硬化症、多囊卵巢综合症、肿瘤、酒精和尼古丁成瘾.最近研究证明纳曲酮具有抗麻醉和治疗纤维肌痛和克罗恩病的作用,超低剂量纳曲酮可以增强麻醉作用.     

雷公藤多甙对佐剂性关节炎模型大鼠ICAM-1的影响

目的:探讨口服雷公藤多甙对大鼠佐剂性关节炎(adjuvant arthritis AA)的治疗作用,以及对外周淋巴器官中细胞黏附分子ICAM-1水平的影响.方法:制备大鼠AA模型,应用免疫组化法检测口服和未口服雷公藤多甙的大鼠淋巴器官中ICAM-1水平的变化;观察口服雷公藤多甙前后关节的肿胀度.结果:口服雷公藤多甙的AA大鼠的外周淋巴器官中ICAM-1的水平明显低于未口服雷公藤多甙的AA大鼠,关节炎症状明显改善.结论:口服雷公藤多甙可以有效降低ICAM-1水平,从而治疗佐剂性关节炎.     

黄芩对小鼠实验性牙周炎血清IgG1和IgG2a水平影响的研究

目的: 本研究采用小鼠建立实验牙周炎模型,观察黄芩水提取物对牙周炎的治疗效果,分析黄芩对Th1 /Th2反应平衡的作用,探讨黄芩对牙周炎的免疫干预/治疗机制。方法: 采用清洁级12周龄雄性昆明小鼠36只,随机分成3组:(1)正常对照组;(2)牙周炎组:参照Kimura等的方法建立牙周炎模型,并于建模后第5周开始用蒸馏水灌胃;(3)黄芩组:同上法复制模型,并于建模后第5周开始用黄芩水提取物灌胃。各组动物分别于建模后第4、6和8周末处死,每组4只。制作牙体牙周组织联合切片,观察牙周的组织学改变,并用ELISA法检测各组小鼠外周血清中IgG1、IgG2a水平。结果: (1)组织学改变:牙周炎组牙周炎症破坏明显。黄芩组牙周组织炎症程度较牙周炎组明显减轻,修复反应明显。(2)抗体水平:黄芩组IgG1水平逐步升高,明显高于牙周炎组(P<0.05)。牙周炎组IgG2a水平逐步升高(P<0.05);黄芩组IgG2a水平逐步降低(P<0.05),且明显低于牙周炎组(P<0.05)。结论: 黄芩通过抑制小鼠牙周炎的Th1细胞反应和增强Th2细胞反应增强小鼠的免疫能力,对小鼠实验性牙周炎有显著的治疗效果。     

Partial correction of the TH2/TH1 imbalance in neonatal murine responses to vaccine antigens through selective adjuvant effects

We have recently shown that neonatal responses to a pannel of vaccine antigens and presentation systems differed qualitatively from adult responses by a bias towards a TH2 pattern. Here we report that a selected adjuvant comprising block copolymers in a water-in-oil emulsion can induce balanced TH1/TH2 responses in BALB/c mice primed at 1 week of age with an immunodominant tetanus peptide vaccine. However, using this specific TH1-driving adjuvant only at time of boosting was not sufficient to fully circumvent the persisting influence of TH2-biased neonatal responses. Unexpectedly also, a significant local toxicity was observed in newborn and young mice, whereas only mild reactions occurred in adults. Thus, although the induction of strong TH1 responses in the neonatal period can be achieved using specific adjuvants, through modulation of the immunological environment present at time of priming, whether such immunization strategies would be safe in the neonatal period remains to be demonstrated. These observations should be taken into consideration in the development of novel vaccines that will have to be already effective early in life.     

Interactive effect of Gm and Km allotypes on cellular immune responses to streptococcal cell wall antigen

Serum samples from 121 unrelated, healthy Japanese individuals were typed for several Gm and Km(1) allotypes. Peripheral blood lymphocytes from these subjects were cultured with streptococcal cell wall (SCW) antigen and the incorporation of 3H-thymidine into T lymphoblasts was measured. Log-linear analysis showed a significant interactive effect of Gm1,17;13,16,21 and Km(1) on the cellular immune response to group A SCW antigen.     

Adjuvant modulation of the immune response of mice against the LcrE protein of Chlamydophila pneumoniae

LcrE protein is a TTSS component of Chlamydophila pneumoniae. The immunogenicity and protective effect of recombinant LcrE protein combined either with Freund's or Alum adjuvant were investigated in mice. The immunization with both protocols resulted in a significant reduction of the number of viable C. pneumoniae in the lungs after challenge. Lower IgG2a/IgG1 ratio in Alum-immunized mice suggested a shift towards Th2 type immune response, but the presence of LcrE-specific IFN-γ-producing cells in LcrE+Alum-immunized mice also indicates Th1 type response. LcrE-specific IgA level was higher in both the sera and the lungs after using Freund's adjuvant. Phenotype of LcrE-specific IFN-γ-producing cells was CD4+ in Alum- and Freund's-immunized mice, but CD8+ cells were also detected in Freund's-immunized mice.These results confirm that LcrE induces protective immunity in mice. The results also show that Alum is able to activate the CD4+ cell-based cellular immunity, thus it can be regarded as an alternative adjuvant during vaccine screening and a useful adjuvant in a potential protein vaccine against C. pneumoniae infection.     

IgE, IgG1, and IgG4 antibody responses to Blomia tropicalis in atopic patients

BACKGROUND: Allergens from house dust mites (HDMs), Dermatophagoides pteronyssinus and Blomia tropicalis are clinically relevant in atopic respiratory diseases in tropical countries. AIMS OF THE STUDY: To evaluate immunoglobulin (Ig)E, IgG1, and IgG4 antibody responses to B. tropicalis in Brazilian atopic patients. METHODS: About 110 patients with allergic rhinitis with/without asthma and 33 control subjects underwent skin prick testing (SPT) with HDM extracts, and their sera were tested for IgE and IgG subclass antibodies to D. pteronyssinus and B. tropicalis by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Most patients (56%) had positive SPT to B. tropicalis extract (B. tropicalis+ group), although 51% were reactive to both B. tropicalis and D. pteronyssinus and 6% were sensitized to B. tropicalis only. IgE-ELISA detected 43%B. tropicalis positivity with high-specific IgE levels in B. tropicalis+ patients. Specific IgG4 levels were higher in B. tropicalis+ than B. tropicalis- groups and correlated with specific IgE levels. The IgG1 levels to B. tropicalis were higher in patients than controls. The major allergenic B. tropicalis components recognized by B. tropicalis+ patient sera were the 54, 66, and 68 kDa proteins. The IgG4-binding protein profiles closely resembled that of IgE. The IgG1 antibodies recognizing multiple B. tropicalis protein species were detected in sera of all three patient groups. CONCLUSIONS: A large percentage of our allergic patients are B. tropicalis+. They are more frequently sensitized to high-molecular weight (HMW) B. tropicalis components than the major low-molecular weight (11-15 kDa) allergens detected in other studies. The results suggest that HMW B. tropicalis antigenic components are potential candidates for evaluating allergen exposure and sensitization, and for immunotherapy treatment.