Immunization to a syngeneic sarcoma by a monoclonal auto-anti-idiotypic antibody

Idiotypic networks regulate the immune response to a variety of antigens. Antibodies generated against other antibodies, called anti-idiotypic antibodies, can themselves mimic antigen and elicit a specific immune response. They have been shown to induce delayed-type hypersensitivity (DTH) to model antigens in the mouse. As anti-idiotypic antibodies are thought to be involved in the response to tumour-associated antigens we tested whether injection of monoclonal antibodies derived from mice hyperimmunized to a syngeneic, chemically induced sarcoma could mimic antigen and induce DTH to the sarcoma in naive mice. One of the monoclonal antibodies, 4.72, primed BALB/c mice for DTH to the sarcoma but not for DTH to another sarcoma or to sheep erythrocytes. Antibody 4.72 did not induce DTH in mice of immunoglobulin allotype congeneic strains nor did it bind to the sarcoma cells. As antibodies specific for this sarcoma have not been detected, we do not know whether idiotype on immunoglobulin molecules is recognized by antibody 4.72. However, as the response induced by antibody 4.72 was both antigen-specific and allotype-restricted, analogous to those induced by anti-idiotypic antibodies in other systems, we propose that antibody 4.72 is an anti-idiotypic antibody.     

FluxExplorer： A general platform for modeling and analyses of metabolic networks based on stoichiometry

An increasing number of genomic and biochemical data make it possible to reconstruct biochemical net-works, especially metabolic networks, of an organelle or even a whole cell. Some methods for metabolism modeling and analyses in this field have been deve…     

Transfer of a functional human immune system to mice with severe combined immunodeficiency

The pressing need for a better experimental system for AIDS research has brought into sharp focus the shortcomings of available animal models and the practical and ethical limitations of studies of immune responses and viral pathogenesis in humans. Current studies of the human immune responses are limited to relatively restrictive in vivo experiments and several in vitro systems that, although useful, allow only short-term studies and support responses to a few antigens. Neither model is particularly amenable to studies of the pathogenesis of diseases of the immune system. We report here that injection of human peripheral blood leukocytes (PBL) can result in the stable long-term reconstitution of a functional human immune system in mice with severe combined immunodeficiency (SCID). Human PBL transplanted to SCID mice increase in number and survive for at least six months; reconstituted mice show spontaneous secretion of human immunoglobulin and a specific human antibody response is induced following immunization with tetanus toxoid. All of the major cell populations present in PBL are found in the lymphoid tissue and blood of SCID recipients, although the relative proportions of B cells, T-cell subsets and monocytes/macrophages in long-term recipients differ from those found in normal PBL and, in mice transplanted with 50 x 10(6) or more PBL from Epstein-Barr virus (EBV)-seropositive donors, EBV-positive B-cell lymphomas often develop. Our results suggest that xenogeneic transplantation of human lymphoid cells into SCID mice may provide a useful model for the study of normal human immune function, the response of the immune system to pathogenic agents and early events in lymphomagensis.     

An IgG autoantibody which inactivates C1-inhibitor

Antibodies are considered to play a specific pathogenic role in certain disease states such as myasthenia gravis, Graves' disease and autoimmune haemolytic anaemia. Autoantibodies which interfere with the function of enzyme cascade systems have also been described in diseases such as acquired haemophilia (anti-factor VIII antibodies) and glomerulonephritis (C3 nephritic factor). The identification of these autoantibodies is crucial to an understanding of the aetiology of such diseases and is also of importance in revealing the inter-relationships of the immune system with other biological pathways. This is the first report of an immunoglobulin G (IgG) autoantibody reactive with C1-inhibitor (C1-Inh), a pivotal inhibitor of the inflammatory response which is known to inactivate proteins of the complement, kinin, fibrinolytic and 'contact phase' systems. This autoantibody was isolated from a patient with a novel variant of acquired angioedema and C1-Inh dysfunction. This finding highlights the involvement of the immune system in the pathogenesis of disorders characterized by the presence of dysfunctional inflammatory response proteins.     

A Toll-like receptor recognizes bacterial DNA

DNA from bacteria has stimulatory effects on mammalian immune cells, which depend on the presence of unmethylated CpG dinucleotides in the bacterial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotides, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like inflammatory response. Accumulating evidence has revealed the therapeutic potential of CpG DNA as adjuvants for vaccination strategies for cancer, allergy and infectious diseases. Despite its promising clinical use, the molecular mechanism by which CpG DNA activates immune cells remains unclear. Here we show that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9. TLR9-deficient (TLR9-/-) mice did not show any response to CpG DNA, including proliferation of splenocytes, inflammatory cytokine production from macrophages and maturation of dendritic cells. TLR9-/- mice showed resistance to the lethal effect of CpG DNA without any elevation of serum pro-inflammatory cytokine levels. The in vivo CpG-DNA-mediated T-helper type-1 response was also abolished in TLR9-/- mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA.     

基于免疫遗传算法的超声电机模糊神经网络控制

针对超声电机参数的时变性、系统内在的非线性和系统的强耦合性等特点,提出基于免疫遗传算法的超声电机模糊神经网络速度控制策略．实验结果表明,与传统模糊神经网络速度控制相比,采用该方法的系统能较好地实现设定的超声电机速度参考模型的自适应跟踪,响应速度脉动小,具有控制灵活、适应性强、控制精度高、鲁棒性强等优点．     

基于免疫反应原理的动态优化算法

生物免疫系统面对复杂的外部环境能够产生相应抗体,快速消除对肌体的威胁,在变化的环境中体现出强大的优化能力和自适应能力.该文借鉴免疫反应机理,提出一种求解动态环境下优化问题的免疫算法.仿真结果表明该算法具有较好的全局优化能力、对环境变化的适应能力强,性能稳定.     

船用锅炉水位模糊免疫自适应PID控制器及仿真

在常规PID控制器的基础上,结合生物免疫反馈机理,引入免疫PID控制算法,进而基于模糊控制理论,设计出一种模糊免疫自适应PID控制器.其中,用模糊免疫反馈P控制器在线整定PID控制器的比例增益,用模糊控制器调整PID控制器的积分时间常数和微分时间常数.并将此控制器应用到船用锅炉水位控制系统中.仿真结果表明,控制器具有很好的快速响应特性和较高的鲁棒性.     

Detection of prokaryotic mRNA signifies microbial viability and promotes immunity

Live vaccines have long been known to trigger far more vigorous immune responses than their killed counterparts. This has been attributed to the ability of live microorganisms to replicate and express specialized virulence factors that facilitate invasion and infection of their hosts. However, protective immunization can often be achieved with a single injection of live, but not dead, attenuated microorganisms stripped of their virulence factors. Pathogen-associated molecular patterns (PAMPs), which are detected by the immune system, are present in both live and killed vaccines, indicating that certain poorly characterized aspects of live microorganisms, not incorporated in dead vaccines, are particularly effective at inducing protective immunity. Here we show that the mammalian innate immune system can directly sense microbial viability through detection of a special class of viability-associated PAMPs (vita-PAMPs). We identify prokaryotic messenger RNA as a vita-PAMP present only in viable bacteria, the recognition of which elicits a unique innate response and a robust adaptive antibody response. Notably, the innate response evoked by viability and prokaryotic mRNA was thus far considered to be reserved for pathogenic bacteria, but we show that even non-pathogenic bacteria in sterile tissues can trigger similar responses, provided that they are alive. Thus, the immune system actively gauges the infectious risk by searching PAMPs for signatures of microbial life and thus infectivity. Detection of vita-PAMPs triggers a state of alert not warranted for dead bacteria. Vaccine formulations that incorporate vita-PAMPs could thus combine the superior protection of live vaccines with the safety of dead vaccines.     

Cell-surface antigens induced by RNA tumour viruses.

Host animals show an immune response to the surface of cells infected with RNA tumour viruses. An element of this response is due to expression of viral structural antigens, but the major part is due to virus-induced cell-surface antigens (CSAs). This article compares the properties of CSAs of the avian, murine and feline retrovirus systems.     

树突状细胞在抗结核分枝杆菌感染中的作用

树突状细胞（Dendritic cells,DCs）是最有效的抗原呈递细胞.DCs能够摄取外来物质,包括结核分枝杆菌（Mycobacterium tuberculosis,MTB）,并将其呈递给效应性淋巴细胞,激发宿主对抗病原微生物感染的免疫反应.因此,树突状细胞与结核分枝杆菌的相互作用在感染初期机体发动免疫应答中十分重要.研究树突状细胞和结核分枝杆菌间的相互作用,有利于从根本上了解细菌-宿主作用机理,为阐明结核分枝杆菌逃避免疫的机制提供依据.     

代谢控制分析的理论与应用

代谢控制分析（ＭｅｔａｂｏｌｉｃＣｏｎｔｒｏｌＡｎａｌｙｓｉｓ，简称ＭＣＡ）是一种以系统观点对细胞内代谢调控进行定量分析的理论和实验方法，结果ＭＣＡ理论，代谢控制是细胞内代谢的系统属性，并可以用酶动力学性质进行定量表示，ＭＣＡ指出了“限速步骤”观念的局限性，认为代谢途径中酶促反应步骤对代谢的控制作用随系统内外条件的改变而变化，用理论计算或试验确定的控制系数能够加深对代谢的控制结构特性的理解，ＭＣＡ     

Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants

Aluminium adjuvants, typically referred to as 'alum', are the most commonly used adjuvants in human and animal vaccines worldwide, yet the mechanism underlying the stimulation of the immune system by alum remains unknown. Toll-like receptors are critical in sensing infections and are therefore common targets of various adjuvants used in immunological studies. Although alum is known to induce the production of proinflammatory cytokines in vitro, it has been repeatedly demonstrated that alum does not require intact Toll-like receptor signalling to activate the immune system. Here we show that aluminium adjuvants activate an intracellular innate immune response system called the Nalp3 (also known as cryopyrin, CIAS1 or NLRP3) inflammasome. Production of the pro-inflammatory cytokines interleukin-1beta and interleukin-18 by macrophages in response to alum in vitro required intact inflammasome signalling. Furthermore, in vivo, mice deficient in Nalp3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) or caspase-1 failed to mount a significant antibody response to an antigen administered with aluminium adjuvants, whereas the response to complete Freund's adjuvant remained intact. We identify the Nalp3 inflammasome as a crucial element in the adjuvant effect of aluminium adjuvants; in addition, we show that the innate inflammasome pathway can direct a humoral adaptive immune response. This is likely to affect how we design effective, but safe, adjuvants in the future.     

The inflammatory reflex

Inflammation is a local, protective response to microbial invasion or injury. It must be fine-tuned and regulated precisely, because deficiencies or excesses of the inflammatory response cause morbidity and shorten lifespan. The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded our understanding of how the nervous system modulates immune responses. The nervous system reflexively regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. The opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.     

运动与促炎性细胞因子

细胞因子是糖基化的多肽。它们介导整个机体的免疫细胞和非免疫细胞之间、器官和器官系统之间及器官、系统内部的联系。炎症性细胞因子包括前炎症性和抗炎症性细胞因子：它们受体育运动、组织损伤和感染等刺激的调节。体育运动可调节局部和全身细胞因子的产生。本综述论述了炎症性细胞因子的作用及细胞因子对运动的反应。同时讨论了IL-6的来源。     

一种粗糙规则化的双因子免疫控制器

根据粗糙集理论原理,从双因子免疫控制器的控制数据中抽取出控制规则,利用本文提出的一种新的规则评价标准筛选出优秀的规则构造控制器,即粗糙规则化的双因子免疫控制器,来对对象进行控制.通过仿真实验证明,粗糙规则化的双因子免疫控制器不但能够体现出普通双因子免疫控制器的学习记忆能力和抗滞后性能,而且在抗干扰性能和响应速度方面都有明显提高.     

癌症的系统生物学模型研究进展

系统生物学研究采用的是系统性的研究方法,即获取并整合目标系统不同层次的生物学信息,构建适用于该生物系统的数学模型,对该系统的特征性行为进行系统性研究.癌症是一种复杂的生物系统,已成为系统生物学研究的热点领域.癌症的系统生物学模型是对传统的癌症动物模型的补充,主要包括:统计推断模型、生化网络模型、以及组织水平模型等.本文综述了这些系统模型方法在癌症研究中的应用情况及其取得的重要研究成果.     

微生物氮代谢调控研究进展

氮素是核酸及蛋白质的主要成分,也是构成生物体的必需元素,对微生物的生长发育、次生代谢以及信息交流等方面均有重要作用.为维持自身的生长发育,不同微生物进化出特有的代谢调控系统,以应对不断变化的氮素供应环境.目前所知的代谢调控方式主要有GlnR、Ntr、sRNA调控系统,但不同的调控系统之间区别甚大.该文综述了几种常见的氮代谢调控系统,以期为深入了解并运用微生物的氮代谢调控机制提供参考.     

Modular enzymes

Although modular macromolecular devices are encountered frequently in a variety of biological situations, their occurrence in biocatalysis has not been widely appreciated. Three general classes of modular biocatalysts can be identified: enzymes in which catalysis and substrate specificity are separable, multisubstrate enzymes in which binding sites for individual substrates are modular, and multienzyme systems that can catalyse programmable metabolic pathways. In the postgenomic era, the discovery of such systems can be expected to have a significant impact on the role of enzymes in synthetic and process chemistry.