基因免疫研究进展

基因免疫的研究已成为免疫治疗研究的热点之一。其产生的机制目前认为主要是注射的ＤＮＡ直接转专职递呈细胞,它可激活ＣＤ４Ｔ细胞、Ｂ细胞和ＣＤ８Ｔ细胞。但也有证据表明ＤＮＡ转染的肌细胞或角质细胞生产抗原后,转送给浸润在附近递呈细胞,激活相应的细胞。ＤＮＡ免疫刺激序列的发现,使人们在基因免疫时应用或设计特殊ＤＮＡ的结构成为可能。细胞因子和共刺激分子是基因免疫中最有前任的生物佐剂。     

梅尼埃病的相关免疫因素研究进展

梅尼埃病的病因至今仍未完全清楚,但近十几年,随着耳免疫学研究的进展和深入,大量实验研究和临床观察结果发现,在部分梅尼埃病患者的发病过程中,免疫学因素起着极其重要的作用,本文就国内外有关梅尼埃病的免疫学研究的新成就加以综述。     

病毒潜伏感染的免疫应答特点

在儿童的早期,单纯疱疹病毒1型能在感觉性神经元中形成潜伏性感染,然后成为复发性疾病的储存场所。在感觉神经元中消灭潜伏的单纯疱疹病毒1型目前尚不可能,但现代研究发现,宿主免疫在维持该病毒潜伏状态上起一定的作用。本文提出证据,证实CD8T细胞调节潜伏状态时单纯疱疹病毒1型基因的表达。     

调节性T细胞研究进展

调节性T细胞（regulatory T cells,Treg）是具有调节功能的成熟T细胞亚群（Akira等．2002）,最初在自身免疫性疾病及肿瘤治疗的免疫学研究中被发现（Shevach等．2000）,因其具有抑制免疫反应的作用,一直被称作抑制性T细胞（Ts）。但随着细胞及分子生物学的飞速发展,Treg分子作用机制逐渐被阐明,其调节功能在机体免疫稳态维持、移植耐受、肿瘤免疫、过敏反应及微生物感染等方面均得到了证实。     

细胞因子在抗病毒免疫中作用的研究进展

近来通过构建编码细胞因子的重组痘苗病毒（ｒＶＶ）感染不同免疫应答状态的小鼠,可以研究细胞因子在体内抗病毒免疫机理中的作用,不仅证实了ＩＦＮ－γ、ＩＮＦ、ＩＬ－２等细胞因子在抗病毒免疫中起重要作用,并对抗病毒免疫机理的传统概念提出了重要的补充与修正。     

治疗自身免疫性疾病的抗细胞因子疫苗

抗细胞因子疫苗是针对疾病相关细胞因子而设计与构建的一类能激发体液免疫应答的主动免疫治疗性疫苗,是用于自身免疫性疾病的一种极具潜力的新型疗法。目前研究与开发的抗细胞因子疫苗主要有2 种类型,一种是通过偶联载体或直接修饰为细胞因子引入外源表位而构建的蛋白疫苗,另一种则是可表达细胞因子免疫原的核酸疫苗。这两类疫苗在临床前及临床研究中,对各种自身免疫性疾病均显现出治疗活性。简介各类抗细胞因子疫苗及其作用机制,综述用于治疗类风湿性关节炎、多发性硬化症、系统性红斑狼疮等各种自身免疫性疾病的抗细胞因子疫苗研究进展。     

白细胞介素18在免疫应答中的作用

白细胞介素18(IL-18)是IL-1细胞因子超家族中的一员,是γ干扰素(IFN-γ)细胞因子产生的主要诱导因子之一[1],在调节机体的免疫反应中起着重要的作用,可调节天然免疫应答和获得性免疫应答,而且也是一个能够在不同的免疫环境中调节Th1或Th2类免疫应答的细胞因子[2].     

抽动障碍临床特点与脑电图关系的研究进展

抽动障碍(Tic disorder,TD)是一种儿童期发病且主要侵犯神经系统的疾病。临床工作中发现部分患儿脑电图(electroencephalogram,EEG)明显异常,提示患儿脑功能障碍与疾病严重程度有关;TD患儿治疗后EEG变化特点也对临床医生选择何种治疗方式有指导意义。     

登革病毒感染的免疫与免疫病理的研究进展

登革病毒感染是世界上热带与亚热带地区一个严重的公众卫生健康问题,本文综述了登革病毒感染后机体免疫的改变,并从抗体、Ｔ细胞激活及细胞因子过量释放方面探讨了登革出血热（ＤＨＦ）／登革休克综合征（ＤＳＳ）的发病机理。     

浅部真菌感染和变态反应性皮肤病相关性研究

目的 通过比较合并与未合并浅部真菌感染的变态反应性皮肤病对常用变应原的敏感性,综合从皮肤或指(趾)甲中分离出的菌种情况,评估浅部真菌感染在变态反应性皮肤病的病因学中的作用.方法 受试者包括353例慢性荨麻疹、湿疹及特应性皮炎患者.通过真菌直接镜检法将受试者分为两组.实验组:变态反应性皮肤病合并浅部真菌感染组(n =173);对照组:变态反应性皮肤病无浅部真菌感染组(n=180).对所有实验组及对照组受试者进行9种真菌变应原和9种非真菌变应原皮内试验.实验组患者进一步进行真菌培养以鉴定菌种.结果 慢性荨麻疹患者实验组须发癣菌、新月弯孢霉,特异青霉、烟曲霉变应原阳性率显著高于对照组(P＜0.05),慢性湿疹患者实验组须发癣菌变应原阳性率显著高于对照组(P ＜0.001).慢性湿疹、荨麻疹患者其他真菌变应原及粉尘螨、屋尘螨等非真菌变应原阳性率比较差异均无统计学意义(P＞0.05).134例患者皮肤或指(趾)甲分离鉴定主要为红色毛癣菌(52.86％)、须癣毛癣菌(14.18％)、絮状表皮癣菌(5.22％)、白念珠菌(6.72％),实验组须发癣菌变应原阳性率及皮肤分离皮肤癣菌阳性率比较差异无统计学意义(P＞0.05).结论 实验结果表明,须发癣菌变应原阳性的慢性荨麻疹、湿疹患者往往合并皮肤癣菌感染,皮肤癣菌感染可能在部分慢性荨麻疹、湿疹的病因学中起重要作用.     

人巨细胞病毒调控免疫逃逸相关基因的功能及其机制研究

人巨细胞病毒（HCMV）是一个广泛传播的机会致病原,也是不断利用和操控机体免疫系统致慢性持续性病毒感染的典型代表。在病毒与宿主共同漫长进化过程中,HCMV产生了许多逃避宿主免疫系统识别的机制,其基因组编码了大量产物,通过抑制自然杀伤细胞和树突细胞功能,下调被感染细胞表面主要组织相容性复合体（MHC）Ⅰ类和Ⅱ类分子表达以减少病毒抗原呈递,损伤IgG介导的体液免疫,调节多种趋化因子和细胞因子的作用,从而控制宿主天然免疫应答和适应性免疫应答的核心功能。本文就HCMV的免疫逃避机制进行综述,探讨病毒与宿主相互作用的发生、发展与结局。     

抽动-秽语综合征动物模型的建立和评价

目的研究建立儿童抽动秽语综合征的动物模型,为基础和临床研究提供支撑。方法实验动物选择刚成年SD大鼠,亚氨基二丙腈腹腔连续注射7 d,采用行为学观察大鼠自主运动和刻板运动评分,液相色谱法测定脑组织DA、NE含量,组织学检查脑组织神经元病理学变化等对模型综合评价。结果模型大鼠的运动行为和刻板运动呈现典型的抽动秽语综合征行为特征,脑组织DA、NE含量以及神经元数目和形态等神经生物学病变明显。结论亚氨基二丙腈腹腔注射可诱发大鼠儿童抽动秽语综合征模型。     

Absence of mitogen-activated protein kinase family member c-Jun N-terminal kinase-2 enhances resistance to Toxoplasma gondii

The function of mitogen-activated protein kinase (MAPK) family member c-Jun N-terminal kinase (JNK)-2 in resistance and pathology during infection has not been greatly studied. Here, we employed Jnk2^−/− mice to investigate the role of JNK2 in resistance and immunity during oral infection with the protozoan pathogen Toxoplasma gondii. We found increased host resistance in the absence of JNK2 as determined by lower parasite burden and increased host survival. Lack of JNK2 also correlated with decreased neutrophil recruitment to the intestinal mucosa and less pathology in the small intestine. In the absence of JNK2, IL-12 production was slightly but significantly increased in restimulated splenocyte populations as well as in purified splenic dendritic cell cultures. These results provide evidence that expression of JNK2 plays a role in T. gondii-induced immunopathology, at the same time in promoting susceptibility to this parasitic pathogen.     

Cytokine synergy: An underappreciated contributor to innate anti-viral immunity

Inflammatory cytokines, such as tumor necrosis factor and the members of the interferon family, are potent mediators of the innate anti-viral immune response. The intracellular anti-viral states resulting from treatment of cultured cells with each of these molecules independently has been well studied; but, within complex tissues, the early inflammatory response is likely mediated by simultaneously expressed mixtures of these, and other, protective anti-viral cytokines. Such cytokine mixtures have been shown to induce potently synergistic anti-viral responses in vitro which are more complex than the simple summation of the individual cytokine response profiles. The physiological role of this ‘cytokine synergy’, however, remains largely unappreciated in vivo. This brief commentary will attempt to summarize the potential effects and mechanisms of anti-viral cytokine synergy as well as present several ‘real-world’ applications where this phenomenon might play an important role.     

变应性鼻炎发病机制研究的新进展

变应性鼻炎是特应性个体接触过敏原后由Ig E介导的I型超敏反应,以鼻腔粘膜为主要效应部位。在此过程中多种炎性细胞(辅助T细胞、嗜酸性粒细胞、嗜碱性粒细胞、肥大细胞等)及细胞因子(IL-4、IL-5、IL-25、IL-33等)构成复杂的网络相互作用,共同促进了AR的发生发展。临床上传统药物治疗及过敏原特异性免疫疗法均有一定的局限性,本文通过对参与过敏性鼻炎发病机制的各个细胞及相关细胞因子的研究进展进行梳理,希望从中发掘出治疗AR的新思路和新靶点。     

TNF superfamily member, TL1A, is a potential mucosal vaccine adjuvant

The identification of cytokine adjuvants capable of inducing an efficient mucosal immune response against viral pathogens has been long anticipated. Here, we attempted to identify the potential of tumor necrosis factor superfamily (TNFS) cytokines to function as mucosal vaccine adjuvants. Sixteen different TNFS cytokines were used to screen mucosal vaccine adjuvants, after which their immune responses were compared. Among the TNFS cytokines, intranasal immunization with OVA plus APRIL, TL1A, and TNF-α exhibited stronger immune response than those immunized with OVA alone. TL1A induced the strongest immune response and augmented OVA-specific IgG and IgA responses in serum and mucosal compartments, respectively. The OVA-specific immune response of TL1A was characterized by high levels of serum IgG1 and increased production of IL-4 and IL-5 from splenocytes of immunized mice, suggesting that TL1A might induce Th2-type responses. These findings indicate that TL1A has the most potential as a mucosal adjuvant among the TNFS cytokines.     

Cytokine release: A workshop proceedings on the state-of-the-science,current challenges and future directions

In October 2013, the International Life Sciences Institute - Health and Environmental Sciences Institute Immunotoxicology Technical Committee (ILSI-HESI ITC) held a one-day workshop entitled, “Workshop on Cytokine Release: State-of-the-Science, Current Challenges and Future Directions”. The workshop brought together scientists from pharmaceutical, academic, health authority, and contract research organizations to discuss novel approaches and current challenges for the use of in vitro cytokine release assays (CRAs) for the identification of cytokine release syndrome (CRS) potential of novel monoclonal antibody (mAb) therapeutics. Topics presented encompassed a regulatory perspective on cytokine release and assessment, case studies regarding the translatability of preclinical cytokine data to the clinic, and the latest state of the science of CRAs, including comparisons between mAb therapeutics within one platform and across several assay platforms, a novel physiological assay platform, and assay optimization approaches such as determination of FcR expression profiles and use of statistical tests. The data and approaches presented confirmed that multiple CRA platforms are in use for identification of CRS potential and that the choice of a particular CRA platform is highly dependent on the availability of resources for individual laboratories (e.g. positive and negative controls, number of human blood donors), the assay through-put required, and the mechanism-of-action of the therapeutic candidate to be tested. Workshop participants agreed that more data on the predictive performance of CRA platforms is needed, and current efforts to compare in vitro assay results with clinical cytokine assessments were discussed. In summary, many laboratories continue to focus research efforts on the improvement of the translatability of current CRA platforms as well explore novel approaches which may lead to more accurate, and potentially patient-specific, CRS prediction in the future.     

IgE crosslinkage of Fcepsilon receptor I induces both production and activation of matrix metalloproteinase-9 in mast cells

Since mast cells play pivotal roles in allergic inflammations, we investigated how IgE-mediated stimulation modulated mast cell matrix metalloproteinase (MMP)-9 production, and its enzymatic activation. In this study, we clearly demonstrated that proMMP-9 released from murine bone marrow-derived cultured mast cells (BMCMC) was activated to its valid form after crosslinking of surface immunoglobulin (Ig)E. Serine protease inhibitors sensitive to chymases inhibited the phenomenon, indicating that certain chymases may be responsible for activation of proMMP-9. Although binding of IgE to its specific receptors did not alter MMP-9 production, the IgE crosslinkage increased both expression of mRNA, and production of MMP-9 in mast cells. Glucocorticoid declined extra cellular processing of proMMP-9 without affecting mRNA expression. These findings give rise to the possibility that production and activation of mast cell MMP-9 may be increased in the affected sites, thereby resulting in an exacerbation of tissue degradation in inflammatory conditions.