天然免疫细胞在急性器官移植免疫排斥中的作用

器官移植免疫排斥反应是一多分子、多细胞参与的复杂免疫应答过程.传统研究主要集中于适应性免疫细胞如T,B细胞在急性移植排斥反应中的作用.近年来,随着对天然免疫细胞亚群、功能及其异质性认识的不断深入,人们发现,除天然免疫细胞在移植免疫应答中的抗原提呈功能及炎性反应以外,其可以发挥直接效应功能,参与移植物的排斥.天然免疫细胞亚群在移植免疫排斥与耐受中的不同作用近来受到重视.本文对天然免疫细胞在急性器官移植免疫排斥和免疫耐受诱导过程中的作用作一简要综述.     

γδT细胞及其治疗感染性疾病的研究进展

γδT细胞是一种高度异质性的T淋巴细胞群,根据其表面抗原受体(TCR)γ、δ链的不同可分为多个亚群.γδT细胞有特殊的发育调控模式,不同类型的γδT细胞在迁移到外周组织之前主要在胸腺中产生.除了在肿瘤、自身性免疫疾病中有重要作用之外,γδT细胞亦参与了细菌、真菌、病毒和寄生虫等感染性疾病的防治进程,是抵抗病原体的第一道...     

CD4+CD25+调节性T细胞与人类获得性免疫缺陷病毒感染

CD4 CD25 是调节性T细胞中功能最重要的一类.它是一类具有特殊免疫调节功能的T细胞亚群.它能够抑制自身免疫病的发生和发展,参与肿瘤免疫的调节,同时在感染和移植免疫中也发挥着极其重要的作用.T细胞的这一亚群具有免疫调节和免疫抑制的特性,新近发现它亦与爱滋病的发生、发展关系密切.HIV进入人体后,CD4 CD25 调节性T细胞抑制了机体的免疫效应但它也同时被感染,最终由于细胞毒的作用而死亡.由于调节性T细胞数量的减少不能有效的发挥其抑制作用,HIV持续的过度活化使得T细胞逐渐耗竭说明在HIV发生、发展的不同阶段Treg细胞可能都发挥了免疫抑制作用,但是却对HIV感染与爱滋病发病的进程产生了不同的效应.此外,CD4 CD25 调节性T细胞还与HIV病毒的持续存在密切相关.本文就CD4 CD25 调节性T细胞与人类获得性免疫缺陷病毒(HIV)感染之间关系进行初步的探讨.     

甲壳动物血细胞及其在免疫防御中的功能

甲壳动物的免疫反应主要依靠吞噬、包囊和凝集,属于非特异性免疫。血细胞在甲壳动物的免疫系统中具有重要作用。造血组织和造血干细胞为血细胞的生成、补充和更新提供了保障。血细胞成熟后分为不同类型,对血细胞分型的研究正在从采用传统的形态学方法向采用生物技术方法的方向发展,单克隆抗体技术已经应用于血细胞分型,结果更为客观准确。不同类型的血细胞在细胞化学特性与功能方面表现出明显差异。在甲壳动物的免疫反应中,血细胞数量在不同的免疫应激状态下发生明显变化。当外来病原体较小时,血细胞通过吞噬作用吞入病原体,在细胞内部将病原杀灭;而当入侵的病原体或寄生虫的个体大于10μm时则以多个血细胞的包囊作用或凝集作用来完成。甲壳动物的免疫反应是一个交互作用的复杂过程,必然涉及多层次、多个因子的参与。其中造血组织的结构,血细胞的产生及调控机理,采用单克隆抗体技术对血细胞进行分型标准的建立,免疫因子在免疫反应中的功能及它们之间的相互作用的网络关系等尚需深入研究。     

甲壳动物血细胞及其在免疫防御中的功能

甲壳动物的免疫反应主要依靠吞噬、包囊和凝集，属于非特异性免疫。血细胞在甲壳动物的免疫系统中具有重要作用。造血组织和造血干细胞为血细胞的生成、补充和更新提供了保障。血细胞成熟后分为不同类型，对血细胞分型的研究正在从采用传统的形态学方法向采用生物技术方法的方向发展，单克隆抗体技术已经应用于血细胞分型，结果更为客观准确。不同类型的血细胞在细胞化学特性与功能方面表现出明显差异。在甲壳动物的免疫反应中，血细胞数量在不同的免疫应激状态下发生明显变化。当外来病原体较小时，血细胞通过吞噬作用吞入病原体，在细胞内部将病原杀灭；而当入侵的病原体或寄生虫的个体大于10 μm时则以多个血细胞的包囊作用或凝集作用来完成。甲壳动物的免疫反应是一个交互作用的复杂过程，必然涉及多层次、多个因子的参与。其中造血组织的结构，血细胞的产生及调控机理，采用单克隆抗体技术对血细胞进行分型标准的建立，免疫因子在免疫反应中的功能及它们之间的相互作用的网络关系等尚需深入研究。     

HnRNP A/B蛋白D亚群的生物学功能

核不均一核糖核蛋白（heterogeneous nuclear ribonucleoproteins, hnRNPs）是一类结合DNA和RNA的核蛋白,并能在核质间穿梭. A/B型hnRNPs（heterogeneous nuclear ribonucleoproteins,hnRNP A/B）是hnRNPs中研究最为清楚的一大类别,生物信息学分析hnRNP A/B可以区分成A和D两个亚群,已鉴定的D亚群主要成员包括hnRNP AB, D和DL. hnRNP A/B的D亚群均含有2个保守的RNA结合结构域（RNA binding domain, RBD）和1个Gly富集区（glycine-rich domain, GRD）,成员间的主要区别在于N端和C端的长度和序列不同. D亚群与pre-mRNA和其它蛋白质结合成微粒系统,参与pre-mRNA的加工、稳定、核输出以及翻译过程. 此外,D亚群也能结合单链和双链DNA,参与转录起始和端粒的稳定. 因此,hnRNP A/B的 D亚群在各个阶段影响基因的表达,在神经系统发育、肿瘤的发生发展及衰老过程中发挥着多样性的功能.     

肠道菌群对肠黏膜T淋巴细胞亚群的调节作用

肠道菌群在肠道免疫稳态中起到了至关重要的作用。大量研究表明肠道菌群通过调节T淋巴细胞亚群的增殖、分化和T细胞亚群分泌不同的细胞因子,可以改变肠道免疫系统的状态。本研究综述了肠道微生物对主要T淋巴细胞亚群的调节作用。     

T细胞应答的代谢特征研究进展

T细胞是参与适应性免疫应答的重要组分之一,它们通过分泌细胞因子或是直接杀伤靶细胞等发挥免疫学功能。未致敏T细胞在参与免疫应答时,会由初始T细胞活化为效应T细胞,之后则发生凋亡或转化为记忆T细胞。研究表明,T细胞的能量代谢方式与其活化与分化有着紧密的联系。不同分化阶段与不同亚群的T细胞在行使其免疫功能时具有不同的代谢特点,并由相关的信号通路调控。本文就T细胞发育、活化、分化、发挥免疫功能等阶段的代谢调节机制进行了阐述,并探讨了T细胞代谢调节在临床诊断与治疗中的应用。     

辅助性T细胞的极化与再极化

激活的ＣＤ4 辅助性Ｔ细胞 (Ｔｈｅｌｐｅｒｃｅｌｌ,Ｔｈ)分化为Ｔｈ1和Ｔｈ2亚群并分别参与不同的免疫应答。Ｔｈ1细胞产生ＩＦＮ γ、ＴＮＦ β和ＩＬ 2并促进对细胞内病原的有效免疫应答 ,但过强的应答导致自身免疫病的发生。Ｔｈ2细胞则产生ＩＬ 4、ＩＬ 5、ＩＬ 6和ＩＬ 1 3并参与清除胞外感染的病原体 ,同时也介导过敏反应。Ｔ细胞亚群的分化及细胞因子表达过程大致可以分为 3个阶段 :( 1 )起始相 ,此过程高度依赖抗原、细胞因子和细胞因子诱导的ＳＴＡＴ因子 ;( 2 )定向相 ,此阶段受亚群特异的转录因子介导 ,在Ｔｈ2细胞为ＧＡＴＡ…     

鳌虾血细胞中一种新的astakine样造血因子基因的克隆及表达

甲壳动物的血细胞参与多种免疫反应,能够激活酚氧化酶原,产生抗菌肽或进行血细胞的封装、吞噬等. 本研究在克氏原螯虾血细胞中发现一种造血激素astakine,是与脊椎动物细胞因子前动力蛋白prokineticin同源的基因,命名为PcAst,该基因的开放阅读框为357 bp,编码118个氨基酸,具有保守的半胱氨酸残基. 半定量PCR结果显示,该基因只在血细胞中表达. 实时荧光定量PCR结果显示,在金黄色葡萄球菌和鳗弧菌刺激后,其mRNA表达量大幅上调. 白斑综合征病毒刺激后,该基因也呈持续上调表达趋势. 为进一步研究其功能,重组表达了PcAst蛋白,并对其蛋白水平表达模式进行了分析. 所有结果表明,该基因可能参与鳌虾血细胞的固有免疫应答反应,在抗细菌和抗病毒中起重要作用.     

Endogenous Molecules Induced by a Pathogen-Associated Molecular Pattern (PAMP) Elicit Innate Immunity in Shrimp

Invertebrates rely on an innate immune system to combat invading pathogens. The system is initiated in the presence of cell wall components from microbes like lipopolysaccharide (LPS), β-1,3-glucan (βG) and peptidoglycan (PG), altogether known as pathogen-associated molecular patterns (PAMPs), via a recognition of pattern recognition protein (PRP) or receptor (PRR) through complicated reactions. We show herein that shrimp hemocytes incubated with LPS, βG, and PG caused necrosis and released endogenous molecules (EMs), namely EM-L, EM-β, and EM-P, and found that shrimp hemocytes incubated with EM-L, EM-β, and EM-P caused changes in cell viability, degranulation and necrosis of hemocytes, and increased phenoloxidase (PO) activity and respiratory burst (RB) indicating activation of immunity in vitro. We found that shrimp receiving EM-L, EM-β, and EM-P had increases in hemocyte count and other immune parameters as well as higher phagocytic activity toward a Vibrio pathogen, and found that shrimp receiving EM-L had increases in proliferation cell ratio and mitotic index of hematopoietic tissues (HPTs). We identified proteins of EMs deduced from SDS-PAGE and LC-ESI-MS/MS analyses. EM-L and EM-P contained damage-associated molecular patterns (DAMPs) including HMGBa, HMGBb, histone 2A (H2A), H2B, and H4, and other proteins including proPO, Rab 7 GPTase, and Rab 11 GPTase, which were not observed in controls (EM-C, hemocytes incubated in shrimp salt solution). We concluded that EMs induced by PAMPs contain DAMPs and other immune molecules, and they could elicit innate immunity in shrimp. Further research is needed to identify which individual molecule or combined molecules of EMs cause the results, and determine the mechanism of action in innate immunity.     

昆虫细胞免疫反应中的吞噬、集结和包囊作用

细胞免疫是昆虫天生免疫系统中很重要的部分, 包括了由血细胞介导的一系列吞噬、 集结和包囊等作用。本文讨论了近年来在昆虫细胞免疫方面的研究进展, 包括参与昆虫细胞免疫的血细胞类型, 识别外来异物的受体因子, 影响免疫活性的一些酶和化学物质等。另外还就吞噬模式, 以及集结和包囊过程中粘附态细胞的形成等加以讨论。     

Physiological functions of hemocytes newly emerged from the cultured hematopoietic organs in the silkworm, Bombyx mori

Abstract  Cellular immunity is a very important part of insect innate immunity. It is not clear if hemocytes entering the hemolymph require a maturation process to become competent. The establishment of a tissue culture system for the insect hematopoietic organs would enable physiological function assays with hemocytes newly emerged from hematopoietic organs. To this end, we established a hematopoietic organ culture system for the purebred silkworm pnd pS and then studied the physiological functions of the newly emerged hemocytes. We found that Grace's medium supplemented with 10% heated silkworm larval plasma was better for culturing the hematopoietic organs of pnd pS . Newly emerged hemocytes phagocytosed propidium iodide-labeled bacteria and encapsulated the Iml-2 coated nickel beads as well as pupal tissue debris. This culture system is therefore capable of generating physiologically functional hemocytes. These hemocytes can be used to study the mechanisms of the hemocyte immune response among others.     

Immune suppression and the cost of reproduction in the ground cricket, Allonemobius socius

One of the most common life history trade-offs in animals is the reduction in survivorship with increasing reproductive effort. Despite the prevalence of this pattern, its underlying physiological mechanisms are not well understood. Here we test the hypothesis that immune suppression mediates this phenotypic trade-off by manipulating reproductive effort and measuring immune function and mortality rates in the striped ground cricket, Allonemobius socius. Because A. socius males provide females with a hemolymph-based nuptial gift during copulation, and many structural components of immunity reside in the hemolymph, we also predicted that sexual selection may differentially affect how disease resistance evolves in males and females. We found that an increased mating effort resulted in a reduced immune ability, coupled with an increased rate in age-specific mortality for both sexes. Thus, immune suppression appears to be a link between reproductive effort and cost in this system. In addition, males and females appeared to differentially invest in several aspects of immunity prior to mating, with males exhibiting a higher concentration of circulating hemocytes and a superior bacterial defense capability. This pattern may be the result of previously established positive selection on gift size due to its affect on female fecundity. In short, female choice for larger gifts may lead to a sexually dimorphic immune ability.     

Contribution of the caspase gene sequence diversification to the specifically antiviral defense in invertebrate

Vertebrates achieve adaptive immunity of all sorts against pathogens through the diversification of antibodies. However the mechanism of invertebrates' innate immune defense against various pathogens remains largely unknown. Our study used shrimp and white spot syndrome virus (WSSV) to show that PjCaspase, a caspase gene of shrimp that is crucial in apoptosis, possessed gene sequence diversity. At present, the role of gene sequence diversity in immunity has not been characterized. To address this issue, we compared the PjCaspase gene sequence diversities from WSSV-free and WSSV-resistant shrimp. The sequence analysis indicated that the PjCaspase gene from the WSSV-resistant shrimp contained a special fragment, designated as fragment 3 (221-229 aa). Down-regulation or overexpression of the PjCaspase gene containing fragment 3 led to significant inhibition or enhancement of virus-induced apoptosis, but had no effect on bacterium challenge. We found evidence that the silencing or overexpression of this gene led to a 7-fold increase or 11-fold decrease of WSSV copies, respectively. Our results suggested that the PjCaspase gene containing fragment 3 provided the molecular basis for the antiviral defense of shrimp. This study represented the first report of the role of gene sequence diversity in the immunity of an invertebrate against virus infection. Invertebrates may employ this gene sequence diversity as a system to avoid pathogen interference with their immune response.     

Enhanced cellular immunity in shrimp (Litopenaeus vannamei) after 'vaccination'

It has long been viewed that invertebrates rely exclusively upon a wide variety of innate mechanisms for protection from disease and parasite invasion and lack any specific acquired immune mechanisms comparable to those of vertebrates. Recent findings, however, suggest certain invertebrates may be able to mount some form of specific immunity, termed 'specific immune priming', although the mechanism of this is not fully understood (see Textbox S1). In our initial experiments, either formalin-inactivated Vibrio harveyi or sterile saline were injected into the main body cavity (haemocoel) of juvenile shrimp (Litopenaeus vannamei). Haemocytes (blood cells) from V. harveyi-injected shrimp were collected 7 days later and incubated with a 1:1 mix of V. harveyi and an unrelated gram positive bacterium, Bacillus subtilis. Haemocytes from 'vaccinated' shrimp showed elevated levels of phagocytosis of V. harveyi, but not B. subtilis, compared with those from saline-injected (non-immunised) animals. The increased phagocytic activity was characterised by a significant increase in the percentage of phagocytic cells. When shrimp were injected with B. subtilis rather than vibrio, there was no significant increase in the phagocytic activity of haemocytes from these animals in comparison to the non-immunised (saline injected) controls. Whole haemolymph (blood) from either 'immunised' or non-immunised' shrimp was shown to display innate humoral antibacterial activity against V. harveyi that was absent against B. subtilis. However, there was no difference in the potency of antibacterial activity between V. harveyi-injected shrimp and control (saline injected) animals showing that 'vaccination' has no effect on this component of the shrimp's immune system. These results imply that the cellular immune system of shrimp, particularly phagocytosis, is capable of a degree of specificity and shows the phenomenon of 'immune priming' reported by other workers. However, in agreement with other studies, this phenomenon is not universal to all potential pathogens.     

Cellular immunosenescence in adult male crickets, Gryllus assimilis

Ecological immunity studies in invertebrates, particularly insects, have generated new insights into trade-offs between immune functions and other physiological parameters. These studies document physiologically directed reallocations of immune costs to other high-cost areas of physiology. Immunosenescence, recognized as the age-related deterioration of immune functions, is another mechanism of radically altering immune systems. We investigated the hypothesis that aging brings on immunosenescence in adult males of the cricket, Gryllus assimilis. Our data show that the intensity of melanotic nodule formation decreased with adult age from after 3-week post-adult emergence. Circulating hemocyte populations similarly decreased from about 5,000 hemocytes/μl hemolymph to about 1,000 hemocytes/μl hemolymph. The numbers of damaged hemocytes in circulation increased from less than 10% at 1-week post-adult emergence to approximately 60% by 3-week post-adult emergence. The composition of hemocyte types changed with age, with increasing proportions of granulocytes and decreasing proportions of plasmatocytes. The declines in nodule formation were not linked to the adult age of sexual behaviors, which begin shortly after entering adulthood in this species. We infer that age-related senescence, rather than cost reallocations, may account for observed declines in various parameters of immune functions in insects, as seen in other animals.     

Double-stranded RNA induces sequence-specific antiviral silencing in addition to nonspecific immunity in a marine shrimp: convergence of RNA interference and innate immunity in the invertebrate antiviral response?

Double-stranded RNA (dsRNA) is a common by-product of viral infections and a potent inducer of innate antiviral immune responses in vertebrates. In the marine shrimp Litopenaeus vannamei, innate antiviral immunity is also induced by dsRNA in a sequence-independent manner. In this study, the hypothesis that dsRNA can evoke not only innate antiviral immunity but also a sequence-specific antiviral response in shrimp was tested. It was found that viral sequence-specific dsRNA affords potent antiviral immunity in vivo, implying the involvement of RNA interference (RNAi)-like mechanisms in the antiviral response of the shrimp. Consistent with the activation of RNAi by virus-specific dsRNA, endogenous shrimp genes could be silenced in a systemic fashion by the administration of cognate long dsRNA. While innate antiviral immunity, sequence-dependent antiviral protection, and gene silencing could all be induced by injection of long dsRNA molecules, injection of short interfering RNAs failed to induce similar responses, suggesting a size requirement for extracellular dsRNA to engage antiviral mechanisms and gene silencing. We propose a model of antiviral immunity in shrimp by which viral dsRNA engages not only innate immune pathways but also an RNAi-like mechanism to induce potent antiviral responses in vivo.