Immunotherapeutic approaches to Alzheimer's disease

Although neurodegenerative diseases such as Alzheimer's disease are not classically considered mediated by inflammation or the immune system, in some instances the immune system may play an important role in the degenerative process. Furthermore, it has become clear that the immune system itself may have beneficial effects in nervous system diseases considered neurodegenerative. Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for the treatment of Alzheimer's disease. These studies have led to human trials that resulted in both beneficial and adverse effects. In animal models, it has also been shown that immunotherapy designed to induce a cellular immune response may be of benefit in central nervous system injury, although T cells may have either a beneficial or detrimental effect depending on the type of T cell response induced. These areas provide a new avenue for exploring immune system-based therapy of neurodegenerative diseases and will be discussed here with a primary focus on Alzheimer's disease. We will also discuss how these approaches affect microglia activation, which plays a key role in therapy of such diseases.     

植物免疫研究进展

众所周知,动物和人类具有免疫能力,但植物在长期的演化过程中,也形成了许多抵抗病原生物侵袭的能力和特性,其中包括植物自身的免疫性.早在100多年前,人们就观察到对植物接种致病菌及一些病菌产物可以使植物产生对相关病害的免疫作用.自20世纪50年代以来,人们陆续发现真菌、细菌、病毒可诱导烟草、蚕豆、豇豆等多种植物产生抵抗病菌的能力,近年来的研究也说明植物自身具有免疫系统.本文主要对植物免疫的演化、诱导因素、免疫机制及在实践中的应用做简略阐述.     

Strategies for enhancing DNA vaccine potency by targeting antigen-presenting cells

The potency of DNA vaccines to stimulate the immune response, especially the T-cell immune response against viral infections and tumors, depends mainly on the ability of antigen-presenting cells to process and present DNA-encoded antigens. Targeting the specific antigen to antigen-presenting cells is believed to be a crucial step for eliciting the T-cell response. Many strategies for enhancing DNA vaccine potency by targeting antigen-presenting cells have been developed. In this article, we generally introduce a T cell immune system and review some strategies which have been recently developed for enhancing DNA vaccine potency.     

Evolution and immunology. The economics of immunity

Our vigilant immune systems are ready to mount an attack as soon as an invading pathogen is spotted. But what is the cost of keeping this sophisticated defense system on red alert? In a provocative Perspective, Read and Allen discuss new findings showing that the cost of immune defense in animals is very high (Moret and Schmid-Hempel), and the claim that, in some circumstances, the cost may be worth the benefit gained (Nunn et al.).     

仔猪免疫系统的建立及早期断奶对仔猪免疫功能的影响研究

新生仔猪获得免疫保护基本来自两方面,一是由母乳中获得的被动免疫;二是在仔猪自身免疫系统发育而形成的主动免疫。早期断奶影响仔猪的免疫功能,造成免疫力下降,严重影响了养猪业的经济效益。本文将对仔猪免疫系统的建立以及断奶对仔猪免疫功能的影响作以综述。     

猪圆环病毒2型的致病机理和疫苗研究进展

为了深入了解猪圆环病毒2型的致病机理和疫苗研究进展,介绍了猪圆环病毒2型感染引起猪免疫系统的损伤过程,其他病原对该过程的促进和诱导作用,刺激免疫系统影响病毒复制和临床病例发生,综述了有关疫苗研究情况。国内外在猪圆环病毒2型的致病机理和疫苗研究进展上有很多相关研究报道,可供借鉴。研究为探讨运用疫苗途径来预防控制该病的发生提供了依据。     

Identification of signal peptide peptidase,a presenilin-type aspartic protease

Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. In humans, SPP activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are recognized by the immune system, and to process hepatitis C virus core protein. We have identified human SPP as a polytopic membrane protein with sequence motifs characteristic of the presenilin-type aspartic proteases. SPP and potential eukaryotic homologs may represent another family of aspartic proteases that promote intramembrane proteolysis to release biologically important peptides.     

乳酸菌对肠道黏膜免疫影响的研究进展

乳酸菌是人和动物体内最常见的原籍2群,其参与维系肠道内2群平衡,通过产生有机酸、细菌素等抗2物质抑制肠道内有害菌的生长.肠道上皮细胞可免疫识别定植在肠道内的乳酸菌及其片段,从而调节肠道黏膜免疫系统,促进淋巴细胞分化、提高sIgA的分泌、调节细胞因子的产生等,对动物机体的固有免疫和获得性免疫具有重要的影响.文章结合国内外研究结果,提出了乳酸2影响肠道免疫的4大前提条件,并从5个方面阐述了乳酸2对肠道黏膜免疫的影响.     

昆虫酚氧化酶作用机制的研究进展

酚氧化酶（Phenoloxidse,PO）是昆虫体内一类重要的氧化酶,在昆虫的正常生长发育过程中具有重要的生理功能。阐述酚氧化酶在昆虫免疫防御及其他生理发育过程中的作用机制,以及可能影响昆虫发育和免疫的诸多因子与酚氧化酶间的关系,以期为进一步探究酚氧化酶对昆虫自身调控机制提供新的思路。     

Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior

The cellular immune response to tissue damage and infection requires the recruitment of blood leukocytes. This process is mediated through a classical multistep mechanism, which involves transient rolling on the endothelium and recognition of inflammation followed by extravasation. We have shown, by direct examination of blood monocyte functions in vivo, that a subset of monocytes patrols healthy tissues through long-range crawling on the resting endothelium. This patrolling behavior depended on the integrin LFA-1 and the chemokine receptor CX(3)CR1 and was required for rapid tissue invasion at the site of an infection by this "resident" monocyte population, which initiated an early immune response and differentiated into macrophages.     

Coordination of early protective immunity to viral infection by regulatory T cells

Suppression of immune responses by regulatory T cells (Tregs) is thought to limit late stages of pathogen-specific immunity as a means of minimizing associated tissue damage. We examined a role for Tregs during mucosal herpes simplex virus infection in mice, and observed an accelerated fatal infection with increased viral loads in the mucosa and central nervous system after ablation of Tregs. Although augmented interferon production was detected in the draining lymph nodes (dLNs) in Treg-deprived mice, it was profoundly reduced at the infection site. This was associated with a delay in the arrival of natural killer cells, dendritic cells, and T cells to the site of infection and a sharp increase in proinflammatory chemokine levels in the dLNs. Our results suggest that Tregs facilitate early protective responses to local viral infection by allowing a timely entry of immune cells into infected tissue.     

民国时期关中地区乡村水利制度的继承与革新——以龙洞——泾惠渠灌区为例进行研究

本文所研究的灌溉区域,远在秦朝时期便有全国最大的灌溉系统——郑国渠,此后历朝历代几乎从未间断,如汉之白渠,唐之郑白渠,北宋之丰利渠,元之王御史渠,明之广惠渠,清之龙洞渠,民国之泾惠渠,直至今天仍有新的泾惠渠灌溉系统在此灌溉农田,福泽一方。在此区域形成的灌溉体系及管理制度随着自然环境及社会环境的变迁,不断地发展变化。对于民国时期此区域内水利制度的研究,有助于帮助我们理清民国时期此区域水利制度发展的脉络,为今天该区域水利制度的改革和发展提供借鉴。     

桑叶多糖提取方法的研究进展

桑叶多糖是从桑叶中提取得到的一种活性物质,具有降血糖、降血脂、抗氧化、抗衰老、增强免疫等多种药理作用,在保健品、医药等行业有较高的开发利用价值。文章从提取原理、方法、优化工艺条件等方面综述了桑叶多糖的5种提取方法,比较了各自的优缺点,认为目前桑叶多糖的提取方法过于单一,粗多糖的纯化仍在一定程度上制约着桑叶多糖的深度开发与利用。指出随着相关研究的不断深入、提取技术的不断完善,桑叶多糖的提取及利用将会更加便捷、高效、安全。     

Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR

A large body of evidence indicates that metazoan innate immunity is regulated by the nervous system, but the mechanisms involved in the process and the biological importance of such control remain unclear. We show that a neural circuit involving npr-1, which encodes a G protein-coupled receptor (GPCR) related to mammalian neuropeptide Y receptors, functions to suppress innate immune responses. The immune inhibitory function requires a guanosine 3',5'-monophosphate-gated ion channel encoded by tax-2 and tax-4 as well as the soluble guanylate cyclase GCY-35. Furthermore, we show that npr-1- and gcy-35-expressing sensory neurons actively suppress immune responses of nonneuronal tissues. A full-genome microarray analysis on animals with altered neural function due to mutation in npr-1 shows an enrichment in genes that are markers of innate immune responses, including those regulated by a conserved PMK-1/p38 mitogen-activated protein kinase signaling pathway. These results present evidence that neurons directly control innate immunity in C. elegans, suggesting that GPCRs may participate in neural circuits that receive inputs from either pathogens or infected sites and integrate them to coordinate appropriate immune responses.     

基于ASP.NET的无规定动物疫病区管理信息系统设计与实现

我国应用管理信息系统技术对无疫区进行疫情监测、疫情上报、疫情预警、数据分析、辅助决策等方面严重不足。规范了无疫区内生产管理活动产生的各类数据,理清了无疫区渔业生产、疫病监测两大管理活动中信息传递过程,建立了无疫区管理信息系统。该系统集成养殖生产、流行病学调查、病原监测、疾病免疫等管理数据,按用户角色提供不同管理功能,将系统内各类数据分类存储和共享,实现以信息化的手段辅助开展无疫区现代化管理。系统采用B/S架构,使用UCML框架式开发平台搭建基于WEB的管理信息系统,用户通过Internet上传和管理数据,通过四种用户角色和五级管理划分用户权限,通过灵活的数据调用功能提供便捷的数据管理,使用SQL Server数据库技术建立了覆盖无疫区内各种管理活动的专业数据库。     

Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.     

B cell ligand discrimination through a spreading and contraction response

B cells recognize foreign antigens by virtue of cell surface immunoglobulin receptors and are most effectively activated by membrane-bound ligands. Here, we show that in the early stages of this process, B cells exhibit a two-phase response in which they first spread over the antigen-bearing membrane and then contract, thereby collecting bound antigen into a central aggregate. The extent of this response, which is both signaling- and actin-dependent, determines the quantity of antigen accumulated and hence the degree of B cell activation. Brownian dynamic simulations reproduce essential features of the antigen collection process and suggest a possible basis for affinity discrimination. We propose that dynamic spreading is an important step of the immune response.     

大学生学业倦怠程度评价指标体系研究

大学生学业倦怠程度评价指标体系是学业预警机制建立的基础。以问卷调查为样本,在分析影响大学生学业倦怠因素的基础上,构建了基于纵向和横向两个维度的大学生学业倦怠程度的动态评价指标体系。纵向指标主要包括专业思想、学习目标与动力、学习习惯与方法、心理状态以及学习效果等5个方面,横向指标则主要反映各个纵向指标的表现程度、持续时间长短及有无泛化情况。该评价指标体系能够动态地反映学生学业倦怠行为的变化过程,从而提高学业预警的过程管理水平,为进一步研究大学生学业倦怠预警机制提供决策依据。     

荔枝胚胎发育机制的探讨

荔枝胚胎发育,有正常型、败育型和部分败育型3类。研究表明,不同类型的胚胎发育状况是可遗传的性状,由一个多基因系统所支配的。在这个基因系统中,某个或几个基因发生突变时,可能导致胚胎发育在某个阶段受到阻遏,使胚胎发育中途停顿,产生败育种子。完全败育型是在胚胎发育早期阶段受阻,故败育时期早,种子极小;部分败育型可能是一种突变杂合体,由于雌雄配子结合子的基因型不同,导致同一植株上果实间胚胎发育状况以及发生败育时期的差异,有的种子发育正常,有的败育;种子大小呈连续的变异状态。