CD4+T细胞的新亚型：Th17细胞及其生物效应

辅助性T细胞通常分为Th1型和Th2型.20余年来,该分类方法形成了理解CD4 T细胞免疫生物学、固有免疫和适应性免疫调节理论的框架.近来研究发现,机体存在一种新型的不同于1型和2型的CD4 效应T细胞——辅助性17细胞(Thelp 17,Th 17),该细胞是由天然T细胞前体分化而来,具有独立的分化和发育调节机制,并特异性地产生白介素17(interleukin 17,IL-17)效应因子,在自身免疫性疾病和感染性疾病中发挥重要调节作用.这将对深入研究机体免疫调节、免疫病理和机体防御反应机制具有重要意义.就这种新型的辅助性T细胞的产生、发育分化机制和免疫调节效应研究进展做一简要综述.     

半乳糖凝集素的结构和功能

半乳糖凝集素的结构和功能关键词半乳糖凝集素凝集素是能与特定糖结构结合的蛋白质,能够识别广泛分布于动物组织中的糖复合物。动物凝集素可分为４类：Ｃ类凝集素（包括选择蛋白,Ｓｅｌｅｃｔｉｎ）、Ｐ类凝集素、正五聚蛋白（Ｐｅｎｔｒａｘｉｎｓ）和半乳糖凝集素（暂...     

模式识别受体在白念珠菌感染中的作用

白念珠菌感染机体后,机体首先通过固有免疫系统来发挥抗真菌作用,模式识别受体是固有免疫细胞用于识别PAMPs的分子,其中Toll样受体和C型凝集素家族是识别白念珠菌的主要PRR。这两类受体被激活后,会通过信号通路启动机体固有免疫和适应性免疫系统,诱导相关细胞因子的产生,募集巨噬细胞、中性粒细胞等吞噬细胞来杀灭白念珠菌,同时,还可传递相关信号诱导Th1、Th2、Th17和Treg等适应性免疫细胞的活化,通过体液免疫和细胞免疫来发挥抗真菌作用,对模式识别受体与白念珠菌相互作用机制的研究对临床真菌病的免疫调节和治疗具有重要意义。     

糖基化与免疫

蛋白质糖基化或聚糖影响免疫细胞和免疫分子的结构与功能,影响机体对抗原的应答反应。聚糖主要有三种免疫功能：首先,糖链对其所连接的糖蛋白起一定稳定作用,保护糖蛋白免受蛋白酶的降解、以及MHC：多肽复合体的装配及折叠等;其二,聚糖及其凝集素受体的相互作用在信号转导、抗原提呈、控制细胞发育与分化中起调控作用;第三,糖链的一些区域可作为抗原识别表位,调控固有免疫和适应性免疫应答。主要介绍了聚糖在抗原提呈和稳定、信号转导、免疫白稳、自身免疫、固有免疫和适应性免疫、等中的功能,以及与免疫相关疾病,如炎症反应、自身免疫性疾病、肿瘤、器官移植排斥、感染性疾病和遗传性疾病的相关性。此外,针对聚糖和糖基转移酶的一些药物分子的治疗应用前景也将一并进行介绍。     

甲状腺激素对适应性免疫细胞的作用

摘要：甲状腺激素（Thyroid hormones,THs）参与免疫功能的调节,在固有免疫和适应性免疫中发挥着重要作用。THs异常分泌所致的免疫功能失调被认为参与了格雷夫斯病和桥本甲状腺炎等自身免疫性疾病的发生发展。目前,THs在固有免疫细胞（中性粒细胞、巨噬细胞、树突状细胞、自然杀伤细胞、肥大细胞）中的作用已得到了较好的阐明,但THs对适应性免疫细胞（T淋巴细胞与B淋巴细胞）的影响等方面的研究仍未引起足够的重视。因此,本研究从适应性免疫细胞的角度出发,重点讨论了THs对这些细胞的发育、分化及功能等方面的影响,为进一步理解THs调节免疫功能的作用提供新视角。     

DC-SIGN与免疫调节

树突状细胞(DC)是目前所知体内功能最强大的专职抗原递呈细胞,它既能启动初始免疫应答,也能负向调控免疫反应,具有独特的免疫调节功能。DC-SIGN属于DC表面C型凝集素受体超家族成员,它既是DC病原体模式识别和黏附受体,又作为DC特征性多功能免疫分子,参与DC免疫调节作用。DC-SIGN在调节DC黏附迁移及炎症反应,激活初始T细胞及启动免疫应答,以及病原体与肿瘤的免疫逃逸等诸多方面发挥重要作用,已日益受到人们的关注。而对DC-SIGN在天然免疫和获得性免疫中调节作用及其相关机制的更深入研究,可为临床相关疾病机制探讨与防治进一步提供新的有力依据和干预途径。     

天花粉中三个同工凝集素的分离纯化及其生物学性质研究

运用阴离子交换层析从亲和纯的天花粉凝集素中分离得到三个同工形式的凝集素,它们都具有结合半乳糖的能力,都能与天花粉凝集素的的因清形成免疫沉淀线,并且其它各方面的性质如疏水结合能力也相仿,对它们生物学性质的检测,发现它们都能杀伤黑色素瘤细胞,但缺乏抑制无细胞蛋白质生物合成的能力,另外,对植物中同工形式凝集素的存在进行了讨论。     

基于凝集素芯片的不同转移潜能肝癌细胞膜蛋白糖谱比较

评估采用凝集素芯片技术寻找肝癌细胞表面侵袭和转移相关特征性糖谱的适用性．首先选取一对模式细胞株(中华仓鼠卵巢细胞CHO和其N-乙酰葡萄糖胺转移酶Ⅰ缺陷株Lec1)验证凝集素芯片系统的可靠性．然后通过凝集素芯片比较正常肝细胞L02、非转移肝癌细胞Hep3B、高转移肝癌细胞HCCLM3的细胞表面糖谱,同时采用细胞凝集素组织化学的方法验证芯片结果．细胞Hep3B和L02相比,对凝集素PHA-L、ConA、AAL、MPL的亲和作用增强而对凝集素WGA的亲和作用减弱,提示在肝癌细胞表面可能出现了增多的复杂寡糖分支、高甘露糖、末端岩藻糖、黏蛋白T抗原和减少的N-乙酰葡萄糖胺和/或多价唾液酸结构．细胞HCCLM3和Hep3B相比,对凝集素LCA、MAL-Ⅰ、MAL-Ⅱ、WGA、PHA-E的亲和作用增强而对凝集素RCA-I的亲和作用减弱,提示在高转移肝癌细胞HCCLM3的表面可能出现了增多的核心岩藻糖、唾液酸(主要是α2-3链接方式)、N-乙酰葡萄糖胺、平分型GlcNAc结构以及减少的末端β1-4链接半乳糖结构．细胞凝集素组织化学的结果支持芯片结果．研究证明,凝集素芯片技术是解析生物学进程中糖谱改变的适用工具．     

关于多发性硬化中浆样树突状细胞的研究进展

多发性硬化是中枢神经系统炎症性自身免疫性疾病的典型代表,以白质脱髓鞘为主要特征。浆样树突状细胞,是专职抗原提呈细胞,是固有免疫和适应性免疫的桥梁,在启动初级免疫应答和维持免疫耐受中发挥了重要作用。由于浆样树突状细胞可以产生大量的细胞因子,特别是Ⅰ型干扰素,所以它与抗炎、免疫调节联系紧密。而目前Ⅰ型干扰素(β)被认为是治疗多发性硬化的有效的免疫调节剂。本文就浆样树突状细胞的来源、特性及其在固有免疫、适应性免疫及免疫耐受中的作用机制进行系统归纳整理,并就其未来发展前景做一简单介绍,为进一步探索免疫调节新机制和寻求多发性硬化新的治疗靶点提供理论依据和基础。     

半乳糖凝集素-1的融合克隆及纯化

目的：表达和纯化半乳糖凝集素-1融合蛋白。方法：用PCR方法从乳腺文库中扩增半乳糖凝集素-1编码序列,将其以正确相位与pGEX-KG载体中的GST编码序列融合,将重组质粒转化大肠杆菌DH5α后,用谷胱甘肽-Sepharose 4B纯化融合蛋白,并用Western印迹检测融合蛋白的表达。结果：构建得到半乳糖凝集素-1的融合蛋白表达载体;Western印迹检测表明,GST-半乳糖凝集素-1融合蛋白成功表达,并纯化得到融合蛋白。结论：克隆和表达了半乳糖凝集素-1基因,并得到纯化的融合蛋白。     

SOCS proteins, cytokine signalling and immune regulation

Suppressor of cytokine signalling (SOCS) proteins are inhibitors of cytokine signalling pathways. Studies have shown that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules positively and negatively regulate macrophage and dendritic-cell activation and are essential for T-cell development and differentiation. Evidence is also emerging of the involvement of SOCS proteins in diseases of the immune system. In this Review we bring together data from recent studies on SOCS proteins and their role in immunity, and propose a cohesive model of how cytokine signalling regulates immune-cell function.     

Murine [corrected] myeloid dendritic cell-dependent toll-like receptor immunity is preserved with aging

The immune response is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this interaction is unclear. Addressing this fundamental question will be critical for the development of effective vaccines for the rapidly rising older subpopulation that manifests increased prevalence of malignancies and infections. Therefore, we undertook the current study to investigate whether aging impairs toll-like receptor (TLR) function in myeloid dendritic cells and whether this leads to reduced T-cell priming. Our results demonstrate that innate TLR immune priming function of myeloid bone marrow derived and splenic dendritic cells (DC) is preserved with aging using both allogeneic and infectious murine experimental systems. In contrast, aging impairs in vitro and in vivo intrinsic T-cell function. Therefore, our results demonstrate that myeloid DCs manifest preserved TLR-mediated immune responses with aging. However, aging critically impairs intrinsic adaptive T-cell function.     

肿瘤相关巨噬细胞极化的研究进展

肿瘤相关巨噬细胞是肿瘤组织局部浸润的巨噬细胞,在肿瘤组织微环境中,这些巨噬细胞发生M2型极化,从而发挥免疫抑制效应,促进肿瘤增殖。而M2型极化的肿瘤相关巨噬细胞也能够被再次诱导逆向极化形成具有抗肿瘤效应的M1型肿瘤相关巨噬细胞,激发机体产生特异性抗肿瘤免疫应答。促进肿瘤相关巨噬细胞M1型极化由此成为当前抗肿瘤免疫防治研究的热点。将对有关肿瘤相关巨噬细胞极化的新进展进行综述,为抗肿瘤免疫研究提供新的思路。     

Establishment of ex vivo systems to identify compounds acting on innate immune responses and to determine their target molecules using transgenic Drosophila

Innate immunity is an evolutionarily conserved self-defense mechanism against microbial infections. In Drosophila, induction of antimicrobial peptides is a major immune response that is regulated by two distinct signaling pathways called the IMD pathway and the Toll pathway, similar to the tumor necrosis factor-alpha signaling and Toll-like receptor/interleukin-1 signaling pathways, respectively, in mammals. In mammals, innate immunity interacts with adaptive immunity and has a key role in the regulated immune response. Therefore, innate immunity is a pharmaceutical target for the development of immune regulators. Previously, based on the striking conservation between the mechanisms that regulate Drosophila immunity and human innate immunity, we established an ex vivo culture in which compounds acting on innate immunity can be evaluated using a reporter gene that reflects activation of the IMD pathway [Yajima et al. [Yajima, M., Takada, M., Takahashi, N., Kikuchi, H., Natori, S., Oshima, Y., Kurata, S., 2003. A newly established in vitro culture using transgenic Drosophila reveals functional coupling between the phospholipase A2-generated fatty acid cascade and lipopolysaccharide-dependent activation of the immune deficiency (imd) pathway in insect immunity. The Biochemical Journal 371(Pt 1), 205-210] Biochem J 371, 205-210]. Here, we combined the ex vivo culture with a reporter gene that reflects the heat shock response and demonstrated that the resulting systems are useful for screening compounds that act specifically on innate immunity, including mammalian innate immune responses. Identification of target molecules is essential for the development of more potent medicines with fewer side effects. In this study, we also established ex vivo systems capable of identifying target molecules of the identified compounds using targeted activation of the IMD pathway.     

Monocyte-derived dendritic cells in innate and adaptive immunity

Monocytes have been classically considered essential elements in relation with innate immune responses against pathogens, and inflammatory processes caused by external aggressions, infection and autoimmune disease. However, although their potential to differentiate into dendritic cells (DCs) was discovered 14 years ago, their functional relevance with regard to adaptive immune responses has only been uncovered very recently. Studies performed over the last years have revealed that monocyte-derived DCs play an important role in innate and adaptive immunity, due to their microbicidal potential, capacity to stimulate CD4(+) and CD8(+) T-cell responses and ability to regulate Immunoglobulin production by B cells. In addition, monocyte-derived DCs not only constitute a subset of DCs formed at inflammatory foci, as previously thought, but also comprise different subsets of DCs located in antigen capture areas, such as the skin and the intestinal, respiratory and reproductive tracts.     

Toll样受体对T细胞功能及代谢的影响

Toll样受体（Toll-like receptors, TLRs）在先天免疫系统中广泛表达,可通过促进抗原提呈细胞（antigen presenting cells,APC）共刺激分子的表达从而间接导致T细胞活化。然而研究发现,TLR也可在T细胞中表达,并可在没有APC的情况下直接调节T细胞的代谢与功能。本文综述了TLR信号对不同T细胞亚群代谢和免疫功能的直接调控作用,为T细胞介导的癌症及自身免疫病等疾病的预防和治疗提供了新的思路。     

Killer dendritic cells and their potential for cancer immunotherapy

Known for years as the principal messengers of the immune system, dendritic cells (DC) represent a heterogeneous population of antigen presenting cells critically located at the nexus between innate and adaptive immunity. DC play a central role in the initiation of tumor-specific immune responses as they are endowed with the unique ability to take up, process and present tumor antigens to naïve CD4⁺ or CD8⁺ effector T lymphocytes. By virtue of the cytokines they produce, DC also regulate the type, strength and duration of T cell immune responses. In addition, they can participate in anti-tumoral NK and NKT cell activation and in the orchestration of humoral immunity. More recent studies have documented that besides their primary role in the induction and regulation of adaptive anti-tumoral immune responses, DC are also endowed with the capacity to directly kill cancer cells. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. First, the direct killing of malignant cells by DC may foster the release and thereby the immediate availability of specific tumor antigens for presentation to cytotoxic or helper T lymphocytes. Second, DC may participate in the effector phase of the immune response, potentially augmenting the diversity of the killing mechanisms leading to tumor elimination. This review focuses on this non-conventional cytotoxic function of DC as it relates to the promotion of cancer immunity and discusses the potential application of killer DC (KDC) in tumor immunotherapy.     

Inhibition of interleukin-12 p40 transcription and NF-kappaB activation by nitric oxide in murine macrophages and dendritic cells

Nitric oxide (NO), an important effector molecule of the innate immune system, can also regulate adaptive immunity. In this study, the molecular effects of NO on the toll-like receptor signaling pathway were determined using interleukin-12 (IL-12) as an immunologically relevant target gene. The principal conclusion of these experiments is that NO inhibits IL-1 receptor-associated kinase (IRAK) activity and attenuates the molecular interaction between tumor necrosis factor receptor-associated factor-6 and IRAK. As a consequence, the NO donor S-nitroso-N-acetylpenicillamine (SNAP) inhibits lipopolysaccharide (LPS)-induced IL-12 p40 mRNA expression, protein production, and promoter activity in murine macrophages, dendritic cells, and the murine macrophage cell line RAW 264.7. Splenocytes from inducible nitric-oxide synthase-deficient mice demonstrate markedly increased IL-12 p40 protein and mRNA expression compared with wild type splenocytes. The inhibitory action of NO on IL-12 p40 is independent of the cytokine IL-10. The effects of NO can be directly attributed to inhibition of NF-kappaB activation through IRAK-dependent pathways. Accordingly, SNAP strongly reduces LPS-induced NF-kappaB DNA binding to the p40 promoter and inhibits LPS-induced IkappaB phosphorylation. Similarly, NO attenuates IL-1beta-induced NF-kappaB activation. These experiments provide another example of how an innate immune molecule may have a profound effect on adaptive immunity.     

MKP-1 Is Necessary for T Cell Activation and Function

MAPKs are evolutionarily conserved immune regulators. MAPK phosphatases (MKPs) that negatively regulate MAPK activities have recently emerged as critical players in both innate and adaptive immune responses. MKP-1, also known as DUSP1, was previously shown to negatively regulate innate immunity by inhibiting pro-inflammatory cytokine production. Here, we found that MKP-1 is necessary in T cell activation and function. MKP-1 deficiency in T cells impaired the activation, proliferation, and function of T cells in vitro, associated with enhanced activation of JNK and reduced NFATc1 translocation into the nucleus. Consistently, MKP-1^−/− mice were defective in anti-influenza immunity in vivo and resistant to experimental autoimmune encephalomyelitis. Our results thus demonstrate that MKP-1 is a critical positive regulator of T cell activation and function and may be targeted in treatment of autoimmune diseases.