细胞因子免疫佐剂效应机制及其在兽医临床中的应用

白细胞介素、干扰素、粒巨噬细胞集落刺激因子等细胞因子作为疫苗的免疫佐剂能增强机体的细胞和体液免疫应答,从而增强疫苗的特异性免疫反应,在细菌、病毒、寄生虫及肿瘤疫苗的研究中具有重要的作用。对细胞因子免疫佐剂的效应机制及其在兽医临床中的应用进展进行阐述,为细胞因子佐剂在兽医临床上的进一步应用提供参考。     

一些新型免疫佐剂的研究进展

免疫佐剂可以理解为能加强抗原的免疫原性和免疫保护效果的物质。这种加强的免疫功能,可表现为增强与其同时使用的特异性抗原的体液免疫反应,也可以表现为增强特异性抗原的细胞免疫反应。近20年来,由于免疫学的进展,亚单位疫苗的开发,特别是肿瘤免疫和疫苗的研究迅速发展,促进了新佐剂研究。传统佐剂虽然副反应低,但对某些抗原没有或仅有很低的免疫增强作用,因而对新型佐剂的研制和开发已成为当今新疫苗研究中的一个非常重要的领域。1细胞因子佐剂细胞因子(cytokine,ck)是由细胞分泌的、能够影响其他细胞功能的多肽,它产生于天然免疫和特异…     

粒细胞-巨噬细胞集落刺激因子基因佐剂对DNA疫苗的免疫调节作用

DNA疫苗具有制备简单,不需要蛋白质的合成、提取与纯化,免疫效果维持时间长,稳定性好,易保存等特点。但由于种与种之间免疫遗传差异,DNA疫苗往往对大动物特别是对哺乳动物的免疫效果不理想。细胞因子常作为基因佐剂用以增强DNA疫苗的免疫原性。粒细胞-巨噬细胞集落刺激因子(GM-CSF)是一个具有多项潜能的造血生长因子,在免疫反应中具有重要作用,编码GM-CSF的质粒能增强DNA疫苗的免疫效果。本文就GM-CSF的分子结构、对增强疫苗免疫原性、协同其他因子作用等方面作一综述。同时介绍了基因佐剂与目的基因表达质粒的构建方案。     

兽医免疫性剂的研究概况

免疫佐剂广义上是指免疫系统的调节剂。佐剂是先于抗原或与抗原同时应用,能非特异性地改变或增强机体对该抗原的特异性免疫应答,能增强该抗原的免疫原性或改变免疫反应类型,而本身并无抗原性的物质。佐剂作用于半抗原或抗原,作用于参与免疫应答的细胞,主要通过增强巨噬细胞活性,促进T细胞或B细胞的反应来行使其作用。佐剂可突出抗原表位,诱导较强的免疫应答;有的使抗原颗粒化而缓慢释放,诱导长时期的免疫应答。研究证叽越来越多的物质被发现有佐剂功能,这些物质主要有以下几类。1油类和无机盐类免疫性剂主要有佛氏佐剂、可降解的…     

蜂胶在食品保鲜和畜禽上的应用前景

3畜禽疾病的防治 蜂胶是特异性和非特异性免疫因子的激活剂，能促进抗体的产生，激活生物体自身的免疫防卫系统，增强巨噬细胞的吞噬能力，提高肌体对有害物质侵入的抵抗力。我国兽医研究人员用蜂胶作为佐剂研制的畜禽疫苗，可增强疫苗的免疫力。     

疫苗佐剂的研究现状和发展趋势

疫苗佐剂是能够非特异性地改变或增强机体对抗原的特异性免疫应答、发挥辅助作用的一类物质.佐剂能够诱发机体产生长期、高效的特异性免疫反应,提高机体保护能力,同时又能减少免疫物质的用量,降低疫苗的生产成本.长期以来,传统疫苗(多为菌体或其裂解物)由于其免疫原性强,佐剂的研究和使用只局限于较小的范围,如毒素和类毒素.     

兽用免疫佐剂的研究现状及发展趋势

免疫佐剂具有调节免疫系统功能,使机体对抗原特异性免疫应答达到非特异性增强或改变,对免疫反应类型改变或使抗原免疫原性增强,但自身没有抗原性物质.佐剂对抗原及参与免疫应答细胞产生作用,通过对巨噬细胞活性的增强,T、B细胞反应促进来发挥自身作用.抗原表位可由佐剂突出,对免疫应答具有较强的诱导;一些会缓慢释放颗粒化抗原,而实现免疫应答的持续诱导.随着研究的深入,很多物质都被发现具有佐剂功能,主要有以下几类.     

免疫佐剂研究进展

佐剂的主要作用是提高抗原(免疫原)的免疫原性和免疫反应的可持续性,它能引导机体的免疫系统对抗原产生体液免疫或细胞免疫反应.对佐剂的选择取决于免疫的目的,从用途上分,佐剂可分为试验用佐剂和疫苗用佐剂.前者主要用于特异性抗体的制备,而后者则作为疫苗的必要成分.文章主要介绍目前常用的几种佐剂包括铝盐佐剂、弗氏佐剂、免疫刺激复合物(ISCOM)、脂质体和CpG及其在科研和疫苗中的应用.     

佐剂在水产疫苗中的研究进展

疫苗接种是控制养殖鱼类病害最为安全有效的方法。但疫苗通常需要佐剂的辅助来提高免疫效力,传统佐剂(如矿物油)已广泛应用于商业化鱼类细菌疫苗中,但这类佐剂可能产生明显的副作用,且对细胞内病原疫苗作用不大。随着鱼类免疫学和免疫机制研究的深入,免疫反应中细胞及细胞因子的功能也逐步明确,为新型疫苗及佐剂的研发提供了基础和前提。为降低鱼类疫苗的副作用,同时确保免疫保护水平,研究人员致力于针对特定宿主细胞反应和特定病原体,开发无副作用或轻微副作用的疫苗佐剂。文章总结了目前水产疫苗常用佐剂以及新一代佐剂(Toll受体配体或细胞因子)的研究进展,重点关注佐剂的免疫保护功效及其在体内对免疫系统的调节作用,为理想水产疫苗佐剂的研发提供参考。     

免疫佐剂研究进展

佐剂的主要作用是提高抗原（免疫原）的免疫原性和免疫反应的可持续性，它能引导机体的免疫系统对抗原产生体液免疫或细胞免疫反应。对佐剂的选择取决于免疫的目的，从用途上分，佐剂可分为试验用佐剂和疫苗用佐剂。前者主要用于特异性抗体的制备，而后者则作为疫苗的必要成分。文章主要介绍目前常用的几种佐剂包括铝盐佐剂、弗氏佐剂、免疫刺激复合物（ISCOM）、脂质体和CpG及其在科研和疫苗中的应用。     

Research Progress on Cytokine Adjuvants

As an adjuvant, cytokine plays a key role in regulating the innate and adaptive immunity and enhancing the vaccine specific immune responses. The researches on the interleukin, interferon, granulocyte macrophage colony stimulating factors, tumor necrosis factors, and chemotactic factor have made considerable progress. Now we reviewed the cytokine adjuvant application in order to provide reference for the future application.     

重组细胞因子在禽类疫苗中的应用进展

细胞因子是免疫系统的重要调节因子,具有明显的免疫佐剂效应。随着鸡细胞因子(IL-2,IL-6,IL-12,IL-18,IFN-γ等)相继克隆成功,重组细胞因子在禽类疫苗中的应用研究也逐步深入。研究表明,用原核、真核载体或者病毒构建的细胞因子重组质粒或表达的重组蛋白,能很好的发挥免疫佐剂的活性。论文综述了细胞因子的免疫增强机制,以及重组细胞因子在现代禽类疫苗中的应用概况。     

细胞因子类佐剂在核酸疫苗中的作用

细胞因子在免疫应答的产生和调节中具有重要作用,可作为免疫佐剂增强疫苗的免疫效果。近年来,重组质粒表达的细胞因子在核酸疫苗研究领域引起了人们广泛的兴趣与关注。文章简述了三类细胞因子在核酸疫苗的研究与应用,探讨了目前应用这些细胞因子类佐剂所存在的问题。     

Toll样受体研究进展

Toll样受体(Toll-like receptors, TLRs)家族在病原体的识别和激活天然免疫方面发挥着非常重要的作用.激活TLRs不仅可以诱导天然免疫应答,而且有利于特异性免疫反应的发生,因而TLRs是天然免疫与获得性免疫之间的桥梁.不同TLRs可以有相同的功能,例如诱导炎性因子的产生或者上调辅助刺激分子的表达,也可以有特异的作用,例如具有诱导IFN-I产生的能力.这些作用不但在抗菌免疫反应中非常关键,而且也表现在自身免疫反应中.因而了解TLRs结构、分布、分类及功能可促进天然免疫机制研究的进一步深入,有利于对变态反应和自身免疫性疾病治疗措施的改进,也有利于解决诸如 CpG佐剂、DNA疫苗、预防过敏反应等实际应用过程中存在的问题.     

Research of the application of a water-in-oil emulsion for the prevention of post-weaning diarrhoea and oedema disease in piglets

A stable water-in-oil emulsion was injected intraperitoneally (i.p.) in piglets about 5 days before weaning to prevent post-weaning diarrhoea (PWD) and oedema disease (OD). So far more than 200,000 piglets have been treated with this adjuvant on a number of farms. On these farms the mortality rate due to PWD and OD decreased, whereas the need for antibiotic treatment declined. Experiments involving alternate application of adjuvant and physiological saline, or adjuvant treatment and no treatment at all, showed a statistically significant positive effect of adjuvant application. The effect of i.p. adjuvant application on specific and non-specific defence mechanisms were examined in well defined rat- and mouse-models, to throw light upon the mechanisms behind the observed adjuvant effect in piglets.     

脂质体佐剂在基因疫苗中的应用

作者论述了脂质体佐剂介导的基因转染机制,脂质体佐剂在基因疫苗中的应用,并对其在基因疫苗中的应用前景进行了展望。     

纳米佐剂的研究进展

自从纳米材料诞生以来,就因其特殊功效而备受瞩目。纳米材料在医学领域中的应用十分广泛,用纳米材料研制疫苗佐剂已成为当前研究的热点。作者从目前常用免疫佐剂存在的问题、纳米佐剂的概念、纳米佐剂的研究进展、前景和展望共4个方面概述了近年来国内外纳米佐剂研究所取得的成果。     

The cytokines of bovine mammary gland: prospects for diagnosis and therapy

The lack of efficacy of conventional strategies for the maintenance of healthy udders in domestic cattle has prompted studies on the use of cytokines for this purpose. The adjuvant use of recombinant bovine cytokines, such as IL-2, IFN-gamma and TNF-alpha, in normal mammary gland, mobilizes innate and acquired immunity. However, stimulated immunity does not prevent or eradicate infection, particularly in the case of Staphylococcus aureus mastitis. Cytokines do, however, improve the bactericidal efficiency of certain antibiotics. The subtle and sensitive changes in the cytokine network of normal and mastitic bovine mammary gland may encourage the use of cytokines in the diagnosis and prognosis of udder health. Numerous studies support this hypothesis, and detection and monitoring of cytokines could become an important alternative management for udder health. The use of cytokines in the immunotherapy, diagnosis and prognosis of mastitis will grow with knowledge of the cytokine network in bovine mammary glands and the development of efficient cytokine diagnostic techniques.     

Heterologous expression of FMDV immunodominant epitopes and HSP70 in P. pastoris and the subsequent immune response in mice

Mycobacterium tuberculosis heat shock protein70 (HSP70) is a major antigen with both chaperone and cytokine functions. It has been used as an adjuvant to induce or potentiate humoral and cellular immunity, both in the form of a mixture with peptide antigens, and as a fusion protein. We have evaluated the effects of HSP70 on foot and mouth virus (FMDV) subunit vaccines. FMDV VP1, and a synthetic multi-epitope FMDV (EG), and VP1-HSP70 and EG-HSP70 fusion proteins were all heterologously expressed in the yeast Pichia pastoris, and used as antigen in mice. The recombinant VP1 and EG alone was able to induce both humoral and marginal cell-mediated immune responses, while the HSP70 fusions markedly enhanced both the humoral and cell-mediated immune responses. The most prominent immune responses arose from vaccination with the EG-HSP70 fusion product. Both fusion protein-induced Th1-like cytokine (IFN-gamma) and Th2-like cytokine (IL-4) were identified.     

Production of biologically active equine interleukin 12 through expression of p35, p40 and single chain IL-12 in mammalian and baculovirus expression systems.

Interleukin-12 (IL-12) is a key cytokine in the development of cell-mediated immune responses. Bioactive IL-12 is a heterodimeric cytokine composed of disulphide linked p35 and p40 subunits. The aim of this study was to verify biologically activity of the products expressed from equine interleukin-12 (IL-12) p35 and p40 cDNAs and to establish whether equine IL-12 could be expressed as a p35/p40 fusion polypeptide, as has been reported for IL-12a of several mammalian species. We report production of equine IL-12 through expression of p35 and p40 subunits in mammalian and insect cells and of a p35:p40 fusion polypeptide in mammalian cells. Conditioned medium recovered from cultures transiently transfected with constructs encoding equine p35 and p40 subunits or single chain IL-12 enhanced IFN-gamma production in cells derived from equine lymph nodes. Preincubation of IFN-gamma inducing preparations with anti-p40 monoclonal antibody resulted in a significant decrease in IFN-gamma induction capacity. Medium recovered from p35 and p40-expressing baculovirus infected cultures enhanced target cell IFN-gamma production and proliferation. Experimental studies in mice and other animals have revealed a therapeutic benefit of IL-12 in cancer, inflammatory and infectious disease and an adjuvant effect in prophylactic regimes. Production of a bioactive species-specific IL-12 is a first step towards an investigation of its potential application in equine species.