猪圆环病毒2型(PCV2):发病机理与先天性免疫的相互作用(续)

上期回顾:上期主要介绍猪圆环病毒基因组的组成和分类(猪圆环病毒1型、猪圆环病毒2型)。1.4来源和进化对植物萎缩病毒和动物圆环病毒的rep基因序列分析发现,植物萎缩病毒和哺乳动物RNA病毒在哺乳动物宿主体内发生过重组,产生了PCV具有功能性的rep基因。因此PCV最初可能从植物萎缩病毒逐步进化,通过宿主转移机制进入哺乳动物、然后与小核糖核酸病毒重组后产生的[36]。细菌中的PCV的DNA不需要Rep’蛋白就能滚环复制,而在哺乳动物细胞中Rep’蛋白是PCV复制必须的[37]。这说明PCVs。

猪圆环病毒2型(PCV2):发病机理及与先天性免疫的相互作用(I)

猪圆环病毒2型(Porcine Circovirus type 2,PCV2)是猪圆环病毒相关疾病(Porcine Circovirus–Associated Disease,PCVAD)的主要病原。病毒对淋巴组织具有嗜性,会导致猪的淋巴系统功能衰竭和免疫抑制。免疫刺激或其他病原共同感染会使该病加重。PCV2寄生在特定的免疫细胞,如巨噬细胞和树突状细胞中,并调节它们的功能。感染猪的IL-10和促炎性细胞因子上调会促进发病。猪的遗传特性将影响其对PCV2的易感性,但是病毒毒力的遗传决定簇目前还不清楚。PCV2 DNA和蛋白质与多种细胞基因相互作用,控制免疫反应,调节病毒的复制和致病。中和抗体和细胞介导免疫是重要的免疫相关保护。虽然目前有有效的疫苗,但是PCV2的变异株不断出现。尽管现在对了解PCV2的致病机理和免疫相互作用已经有了很大的进步,但仍旧存在很多问题有待解决。

猪圆环病毒2型(PCV2):发病机理及与先天性免疫的相互作用(Ⅲ、续完)

上期主要介绍猪圆环病毒临床疾病(猪圆环病毒相关疾病、同事感染其他猪病病原)、治病机理(淋巴衰竭和免疫抑制)。

斑马鱼胸苷酸合成酶与自身mRNA的相互作用

斑马鱼(zebrafish,Danio rerio)是生物学领域中公认的研究脊椎类生物的模式生物.胸苷酸合成酶(thymidylate synthase,TS)是DNA从头合成的限速酶,多年来一直作为肿瘤化疗的重要靶酶.前期的研究表明,人和大肠杆菌中TS能与自身的mRNA结合,在翻译水平上具有反馈抑制自调控现象.斑马鱼作为药物模型的研究已成为热点研究领域,为了探讨斑马鱼的胸苷酸合成酶的调控规律,以及与人TS的相关性,利用原核表达,纯化获得高均一性斑马鱼TS蛋白,采用凝胶迁移研究了TS和其mRNA的体外结合,采用免疫共沉淀:RT-PCR技术研究了它们在体内的相互作用,实验结果表明,斑马鱼的TS在体内外均与自身的mRNA存在特异性的相互作用.研究说明,斑马鱼和人的TS具有高度生物学过程相关性,为构建斑马鱼抗肿瘤药理模型提供了理论基础.

突触体素、S-100蛋白、NSE免疫反应神经纤维在人淋巴结的分布

探讨突触体素、 S- 10 0蛋白、 NSE免疫反应神经纤维在人淋巴结的分布 ,为淋巴结的神经免疫相互作用提供形态学资料。应用免疫组织化学 ABC法观察人类腹股沟、腋窝、肠系膜、肺等淋巴结 40例 ,10 %福尔马林固定 ,石蜡包埋组织切片。结果显示 :突触体素、 S- 10 0蛋白、 NSE免疫反应神经纤维呈细丝状沿被膜和门部结缔组织小梁及血管进入皮质后主要分布于副皮质区 ,环绕淋巴小结 ,进一步分支到达髓质。同时在淋巴小结生发中心及副皮质区有 S- 10 0蛋白免疫反应阳性细胞。在髓质髓窦内有 NSE免疫反应阳性细胞。结论 :淋巴结内有突触体素、 S- 10 0蛋白、 NSE免疫反应神经纤维的支配 ,并有 S- 10 0蛋白、 NSE免疫反应阳性细胞 ,为淋巴结的神经免疫相互作用提供形态学资料。

玫瑰痤疮的发病机制

玫瑰痤疮发病机制至今尚未完全清楚。本病可能在一定遗传因素的基础上，由多种因素诱导的以天然免疫、神经免疫相互作用及血管舒缩异常为主导的慢性炎症。发生机制主要有以下几个方面：

Verification of the Interaction between SET and eEF1A1 in Human Liver Cells by Co-immunoprecipitation

[Objective] The aim was to investigate the possible interaction between SET and eEF1A1 in human liver cells. [Method] Firstly the total proteins of human L-02 liver cells were extracted under non-denaturing conditions; then,mouse anti-human SET and rabbit anti-human eEF1A1 antibodies were used to perform the co-immunoprecipitation respectively; subsequently,the immunoprecipitations was correspondingly detected with rabbit anti-human eEF1A1 and mouse anti-human SET antibodies by Western Blot. [Result] EEF1A1 was detected in protein complex from the immunoprecipitations by using anti-SET antibody,and SET also was detected in immunoprecipitations by using anti-eEF1A1 antibody. [Conclusion] The interaction between SET and eEF1A1 in human liver cells was confirmed.

Inflammatory bowel disease requires the interplay between innate and adaptive immune signals

Inflammatory bowl disease （IBD） is a type 1 T helper cell （Th1）-mediated autoimmune disease. Various studies have revealed that environmental pathogens also play a significant role in the initiation and progression of this disease. Interestingly, the pathogenesis of IBD has been shown to be related to nitric oxide （NO） released from innate immune cells. Although NO is known to be highly toxic to the gut epithelia, there is very little information about the regulation of NO production, One major question in the etiology of IBD is how Thl cells and pathogens interact in the induction of IBD. In present study, we focused on the regulation of NO. We show that macrophages require both interferon-γ, （IFN-γ）-mediated and TLR4-mediated signals for the production of NO, which causes inflammation in the intestine and subsequently IBD. Thus, IBD is the result of concerted actions of innate immune signals, such as the binding of LPS to TLR-4, and adaptive immune signals, such as IFN-γ produced by Thl cells.

Interplay between hepatitis B virus and the innate immune responses:implications for new therapeutic strategies

Hepatitis B virus(HBV) infection is still a worldwide health problem;however,the current antiviral therapies for chronic hepatitis B are limited in efficacy.The outcome of HBV infection is thought to be the result of complex interactions between the HBV and the host immune system.While the role of the adaptive immune responses in the resolution of HBV infection has been well characterized,the contribution of innate immune mechanisms remains elusive until recent evidence implicates that HBV appears to activate the innate immune response and this response is important for controlling HBV infection.Here,we review our current understanding of innate immune responses to HBV infection and the multifaceted evasion by the virus and discuss the potential strategies to combat chronic HBV infection via induction and restoration of host innate antiviral responses.

Role of genetics in the diagnosis and prognosis of Crohn's disease

Considering epidemiological,genetic and immunological data,we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease.It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation.Several genes have been so far related to the diagnosis of Crohn's disease.Those genes are related to innate pattern recognition receptors,to epithelial barrier homeostasis and maintenance of epithelial barrier integrity,to autophagy and to lymphocyte differentiation.So far,the most strong and replicated associations with Crohn's disease have been done with NOD2,IL23R and ATG16L1 genes.Many genes have so far been implicated in prognosis of Crohn's disease and many attempts have been made to classify genetic profiles in Crohn's disease.CARD15 seems not only a susceptibility gene,but also a disease-modifier gene for Crohn's disease.Enriching our understanding on Crohn's disease genetics is important but when combining genetic data with functional data the outcome could be of major importance to clinicians.

Complement and its role in innate and adaptive immune responses

The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.

Innate and adaptive immunity in inflammatory bowel disease

Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time. Functional studies from in vivo models of intestinal inflammation as well as results from genome-wide association studies strongly suggest a crossregulation of both arms. The present review will illustrate this interaction by selecting examples from innate immunity and adaptive immunity, and their direct impact on each other. Broadening our view by focusing on the cross-regulated areas of the mucosal immune system will not only facilitate our understanding of disease, but furthermore will allow identification of future therapeutic targets.

Expression of CyclinD1／Bcl-1 and p27／Kip1 in Gliomas： Their Correlation with Pathological Grade and Prognosis

Objective: To study cyclinD1/bcl-1 and p27/kip1 expression in gliomas and their correlation with pathological grade and prognosis. Methods: Immunohistochemical technique was used to detect the cyclinD1/bcl-1 and p27/kip1 expression in 48 human brain glioma tissues of different malignant grades, and 12 normal non-neoplastic tissues collected from internal decompression. The data were analyzed quantitatively by the image system and also correlated retrospectively with the patients' clinical characteristics. Results: The immunohistochemical reaction for cyclinD1/bcl-1 and p27/kip1 was confined to the nuclei. The abnormal positive expression rates of both cyclinD1/bcl-1 and p27/kip1 in gliomas were found higher than that in non-neoplastic tissues(P<0.05). The number and staining intensity of cyclinD1/bcl-1 positive nuclei increased with malignant grades (P<0.05). On the contrary, the positive nuclei of p27/kip1 expression decreased in number and staining intensity with malignant grades(P<0.05). Higher expression of cyclinD1/bcl-1 or/and lower expression of p27/kip1 were associated with poor prognosis(P<0.05). Conclusion: The abnormal expression of both cyclinD1/bcl-1 and p27/kip1 might be closely related to the occurrence and development of gliomas and they might have synergistic effect. These data suggest that both cyclinD1/bcl-1 expression and p27/kip1 expression can act as an independent prognostic factor.

Liver angiogenesis: tumor host interaction in non-metastatic colorectal cancer

Objective: Angiogenesis is a crucial step for tumor growth and progression. Changes of liver angiogenesis (without metastatic invasion) in response to primary tumors are not known. The aim of the study was to investigate the liver angiogenesis in non-metastatic colorectal cancer (CRC). Methods: Human colorectal adenocarcinoma tumors were grown subcutaneously in nude mice. All animals showed tumor growth locally without macroscopic or microscopic evidence of liver metastases. Livers were investigated for their microvessel density (MVD) at different stages of tumor growth (as small, medium, and large-sized tumors). Normal non-tumor-bearing mice served as controls. To assess MVD, two endothelial cell markers (anti-CD34 and -CD31 antibodies), image analysis, and immunofluorescent technique were utilized. Enumeration of positive stained endothelial cells revealed the MVD. Results: Non-metastatic livers showed increased levels of MVD vs. control. Moreover, levels of MVD were higher in small and medium-sized tumor groups versus large sized tumor groups. Conclusion: The present data indicate that angiogenesis in the liver is induced in early-stages of CRC. However, this effect is suppressed with advanced tumor growth. These results provide an additional rationale for including antiangiogenic therapy in the treatment of early stages of CRC.

A Mathematical Model of Breast Cancer and Mediated Immune System Interactions

Mathematical model that describes breast cancer and immune interactions were presented using system of differential equations to provide analytic and nnmeric framework of cancer-immune dynamics. Four types of immune cells-CTLs （cytotoxic T lymphocytes）, macrophages, NK （natural killer） and helper T cells-known to play the most significant roles in developing breast cancer immunity were modeled using differential equations. The model was then applied to different cancer growth rates and simulated using MATLAB software tool. The parameters of the model were based on experimental and clinical results from published articles. Results supported clinical studies that maximal breast cancer immunity depends mostly on each of the four immune cell types chosen. It was observed that for a given breast cancer growth rate, there was an optimal activation that maximized the response of the immune system. The effectiveness of the immune system resulted in the decrease in breast cancer killing rates. These results highlighted the importance of immune system activations in breast cancer development and treatment. Therefore, the model and its simulation provided a robust framework to better understand breast cancer progression and response to the immune system.

神经-免疫调控在呼吸道疾病中的研究进展

神经系统和免疫系统相对独立又相互作用,神经-免疫调控对于呼吸系统抵御外界有害刺激、维持稳态至关重要。神经-免疫之间密切关联、相互作用,参与了呼吸道疾病的发生与发展过程,形成了对炎症等反应监测和调节的环路。本文综述呼吸系统的神经-免疫调控及其在呼吸道疾病中的作用,为深入了解神经-免疫的交联效应、探索其在呼吸道疾病中的作用机制提供理论基础,为呼吸系统疾病的防治提供新思路。

温督通阳论治酒渣鼻

酒渣鼻又称玫瑰痤疮，是一种好发于面中部的慢性炎症。主要表现为面部阵发性潮红，持久性红斑、丘疹、脓疱，毛细血管扩张等，少部分在鼻部出现赘生物。临床上可分为红斑毛细血管扩张型、丘疹脓疱型、肥厚增生型与眼型。本病的发病机制涉及天然免疫异常、神经免疫相互作用、神经脉管调节异常、微生物诱发炎症反应与皮肤屏障障碍等埋。由于本病对容貌影响较大，致患者自卑、焦虑、社交恐惧等。笔者现对温督通阳论治酒渣鼻的思路进行分析。

Roles and regulations of the ETS transcription factor ELF4/MEF

Most E26 transformation-specific （ETS） transcription factors are involved in the pathogenesis and progression of cancer. This is in part due to the roles of ETS transcription factors in basic biological processes such as growth, proliferation, and differentiation, and also because of their regulatory functions that have physiological relevance in tumorigenesis, immunity, and basal cellular homoeostasis. A member of the E74-1ike factor （ELF） subfamily of the ETS transcription factor family--myeloid elf-l-Uke factor （MEF）, designated as ELF4~has been shown to be critically involved in immune response and signalling, osteogenesis, adipo- genesis, cancer, and stem cell quiescence. ELF4 carries out these functions as a transcriptional activator or through interactions with its partner proteins. Mutations in ELF4 cause aberrant interactions and induce downstream processes that may lead to dis- eased cells. Knowing how ELF4 impinges on certain cellular processes and how it is regulated in the cells can lead to a better understanding of the physiological and pathological consequences of modulated ELF4 activity.

NK cells play a significant role in immunosurveillance at the early stage of MLL-AF9 acute myeloid leukemia via CD226/CD155 interactions

Acute myeloid leukemia(AML) is an aggressive hematological malignancy, and the mechanism underlying immune system involvement in leukemia development is unclear. In the present study, we utilized a myeloid/lymphoid or mixed-lineage leukemia; translocated to, 3(MLLT3/MLL-AF9)-induced AML mouse model with or without exposure to irradiation. We found that the leukemia cells could survive and expand in hosts with intact immune systems, whereas leukemia progression was accelerated in mice with impaired immune systems. Moreover, the leukemia cells escaped from host immunosurveillance via editing their immunogenicity, including the up-regulation of an inhibitory antigen(i.e., CD47) and the down-regulation of active antigens(i.e., CD86, CD54, retinoic acid early transcript(RAE), histocompatibility 2, D region locus b(H2-Db) and H2-Dd). Natural killer(NK) cells were activated in the early phase of AML progression, whereas T cells were stimulated in the late phase. Furthermore, NK cell depletion showed that NK cells were necessary for the elimination of leukemia cells in our AML mouse model. Notably, CD155/CD226 primarily mediated the interaction between NK cells and leukemia cells and contributed to the antitumor effects of NK cells during the early phase of AML. Clinical data from patients with diverse hematological malignancies showed that CD155 expression was decreased in hematological malignancies. Taken together, our results demonstrate that NK cells play a pivotal role in immunosurveillance against leukemia cells during the early stage of AML primarily through the CD226/CD155 interaction; however, NK cells are not sufficient to eliminate leukemia cells.

Paneth cells: the hub for sensing and regulating intestinal flora

The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides in the intestine under steady-state conditions, play a vital role in regulating intestinal flora. Many studies on inflammatory bowel disease(IBD)-associated genes have put Paneth cells at the center of IBD pathogenesis. In this perspective, we focus on mechanistic studies of different cellular processes in Paneth cells that are regulated by various IBD-associated susceptibility genes, and we discuss the hypothesis that Paneth cells function as the central hub for sensing and regulating intestinal flora in the maintenance of intestinal homeostasis.