Plant pathogens and integrated defence responses to infection.

Plants cannot move to escape environmental challenges. Biotic stresses result from a battery of potential pathogens: fungi, bacteria, nematodes and insects intercept the photosynthate produced by plants, and viruses use replication machinery at the host's expense. Plants, in turn, have evolved sophisticated mechanisms to perceive such attacks, and to translate that perception into an adaptive response. Here, we review the current knowledge of recognition-dependent disease resistance in plants. We include a few crucial concepts to compare and contrast plant innate immunity with that more commonly associated with animals. There are appreciable differences, but also surprising parallels.     

Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium

A well recognized feature of the immune response to parasitic helminth infections, including schistosomiasis, is the production of large amounts of specific and nonspecific IgE1,2. Immunological pathways involving IgE can lead to damage to the developing schistosomulum and it has been suggested that responses involving IgE could have evolved as protection against helminth infections. There has been no epidemiological evidence to support this idea and the only significant IgE responses known in man are those involved in the pathogenesis of allergic disease. Here we measure serological response during reinfection with S. haematobium and demonstrate that IgE antibodies in man can be beneficial. Our results support the hypothesis that the slow build-up of IgE to high levels and the early production of IgG4 antibodies, which may block IgE pathways are responsible for delaying the development of protective immunity to S. haematobium.     

Chitin induces accumulation in tissue of innate immune cells associated with allergy

Allergic and parasitic worm immunity is characterized by infiltration of tissues with interleukin (IL)-4- and IL-13-expressing cells, including T-helper-2 cells, eosinophils and basophils. Tissue macrophages assume a distinct phenotype, designated alternatively activated macrophages. Relatively little is known about the factors that trigger these host responses. Chitin, a widespread environmental biopolymer of N-acetyl-beta-D-glucosamine, provides structural rigidity to fungi, crustaceans, helminths and insects. Here, we show that chitin induces the accumulation in tissue of IL-4-expressing innate immune cells, including eosinophils and basophils, when given to mice. Tissue infiltration was unaffected by the absence of Toll-like-receptor-mediated lipopolysaccharide recognition but did not occur if the injected chitin was pre-treated with the IL-4- and IL-13-inducible mammalian chitinase, AMCase, or if the chitin was injected into mice that overexpressed AMCase. Chitin mediated alternative macrophage activation in vivo and the production of leukotriene B(4), which was required for optimal immune cell recruitment. Chitin is a recognition element for tissue infiltration by innate cells implicated in allergic and helminth immunity and this process can be negatively regulated by a vertebrate chitinase.     

Characterization of the heteroepitaxial growth of 3C-SiC on Si during low pressure chemical vapor deposition

3C-SiC heteroepitaxial layers were grown on Si substrates using a horizontal, hot-wall low pressure chemical vapor deposition system. The crystal quality, surface morphology and thickness uniformity of the layers were characterized by X-ray diffraction, atomic force microcopy and Fourier transform infrared spectroscopy, respectively. Growth of the epitaxial layer was determined to follow a three-dimensional island mode initially and then switch to a step-flow mode as the growth time increases. Barrier epithelia, especially airway epithelial cells, are persistently exposed to micro-organisms and environmental factors. To protect the host from these microbial challenges, many immune strategies have evolved. The airway epithelium participates in the critical innate immune response through the secretion of immune effectors such as mucin, antimicrobial peptides (AMP), and reactive oxygen species (ROS) to entrap or kill invading microbes. In addition, airway epithelial cells can act as mediators connecting innate and adaptive immunity by producing various cytokines and chemokines. Here, we present an overview of the role of mucosal immunity in airway epithelium, emphasizing the framework of bacterial and viral infections along with regulatory mechanisms of immune effectors in human cells and selected animal models. We also describe pathophysiological roles for immune effectors in human airway disease.     

Refractory periods and climate forcing in cholera dynamics

Outbreaks of many infectious diseases, including cholera, malaria and dengue, vary over characteristic periods longer than 1 year. Evidence that climate variability drives these interannual cycles has been highly controversial, chiefly because it is difficult to isolate the contribution of environmental forcing while taking into account nonlinear epidemiological dynamics generated by mechanisms such as host immunity. Here we show that a critical interplay of environmental forcing, specifically climate variability, and temporary immunity explains the interannual disease cycles present in a four-decade cholera time series from Matlab, Bangladesh. We reconstruct the transmission rate, the key epidemiological parameter affected by extrinsic forcing, over time for the predominant strain (El Tor) with a nonlinear population model that permits a contributing effect of intrinsic immunity. Transmission shows clear interannual variability with a strong correspondence to climate patterns at long periods (over 7 years, for monsoon rains and Brahmaputra river discharge) and at shorter periods (under 7 years, for flood extent in Bangladesh, sea surface temperatures in the Bay of Bengal and the El Ni?o-Southern Oscillation). The importance of the interplay between extrinsic and intrinsic factors in determining disease dynamics is illustrated during refractory periods, when population susceptibility levels are low as the result of immunity and the size of cholera outbreaks only weakly reflects climate forcing.     

A systems biology analysis of the Drosophila phagosome

Phagocytes have a critical function in remodelling tissues during embryogenesis and thereafter are central effectors of immune defence. During phagocytosis, particles are internalized into 'phagosomes', organelles from which immune processes such as microbial destruction and antigen presentation are initiated. Certain pathogens have evolved mechanisms to evade the immune system and persist undetected within phagocytes, and it is therefore evident that a detailed knowledge of this process is essential to an understanding of many aspects of innate and adaptive immunity. However, despite the crucial role of phagosomes in immunity, their components and organization are not fully defined. Here we present a systems biology analysis of phagosomes isolated from cells derived from the genetically tractable model organism Drosophila melanogaster and address the complex dynamic interactions between proteins within this organelle and their involvement in particle engulfment. Proteomic analysis identified 617 proteins potentially associated with Drosophila phagosomes; these were organized by protein-protein interactions to generate the 'phagosome interactome', a detailed protein-protein interaction network of this subcellular compartment. These networks predicted both the architecture of the phagosome and putative biomodules. The contribution of each protein and complex to bacterial internalization was tested by RNA-mediated interference and identified known components of the phagocytic machinery. In addition, the prediction and validation of regulators of phagocytosis such as the 'exocyst', a macromolecular complex required for exocytosis but not previously implicated in phagocytosis, validates this strategy. In generating this 'systems-based model', we show the power of applying this approach to the study of complex cellular processes and organelles and expect that this detailed model of the phagosome will provide a new framework for studying host-pathogen interactions and innate immunity.     

致敏花粉的研究及应用前景

花粉症属于环境性疾病,凡有植物生长的地方,均可能有花粉症病人。我国地域辽阔,植被种类繁多,空气中致敏花粉亦极为多样。调查掌握我国各地方空气当中致敏花粉的类别及其在一年四季的出现规律,对防止花粉过敏症将是一个重要的基础工作。我国对花粉致敏的研究已有了初步规模,为我国花粉过敏病症等一些异常性疾病的流行病学的研究和临床诊治及预防提供了有价值的参考依据。     

基于免疫多样性的分布式入侵检测算法

提出了一种基于免疫多样性的分布式入侵检测方法，将支持向量机（SVM）作为抗体对入侵行为进行检测．首先，采用随机子空间方法生成多样化的SVM个体，再用人工免疫算法进化个体，然后通过引入Q统计量和互信息作为抗体多样性的度量，由此得到的检测器种群具有知识互补性，最后用集成的思想将种群中各检测器的结论进行合成．数值实验表明，所提方法生成的抗体更具多样性，检测精度高于单个SVM和Bagging方法，其分布式并行检测特性有利于加强检测系统的健壮性．     

Autophagy in immunity and inflammation

Autophagy is an essential, homeostatic process by which cells break down their own components. Perhaps the most primordial function of this lysosomal degradation pathway is adaptation to nutrient deprivation. However, in complex multicellular organisms, the core molecular machinery of autophagy - the 'autophagy proteins' - orchestrates diverse aspects of cellular and organismal responses to other dangerous stimuli such as infection. Recent developments reveal a crucial role for the autophagy pathway and proteins in immunity and inflammation. They balance the beneficial and detrimental effects of immunity and inflammation, and thereby may protect against infectious, autoimmune and inflammatory diseases.     

复方健胃消食浸膏粉免疫调节作用的实验研究

 目的 探讨复方健胃消食浸膏粉对小鼠的免疫调节作用,开发传统中药复方制剂新的保健价值。方法 给予6-8周龄,18-22g,雌性BALB/C 小鼠复方健胃消食浸膏粉,设一个对照组和剂量分别为0.2g/kg.bw、0.6g/kg.bw和1.8g/kg.bw的三个干预组,干预30天后,进行细胞免疫、体液免疫和NK细胞功能检验,测定脾脏T淋巴细胞增殖能力、迟发变态反应(DTH)的程度、抗体生成数、半数溶血值（HC50）和NK细胞的活性。结果 与对照组相比,复方健胃消食浸膏粉能明显增加小鼠T淋巴细胞的增殖能力和DTH的程度,提高小鼠抗体生成数和NK细胞的活性。结论 复方健胃消食浸膏粉具有增强小鼠细胞免疫、体液免疫和NK细胞活性的功能。     

The genome sequence of Atlantic cod reveals a unique immune system

Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC)?II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC?II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC?I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC?II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.     

Indoor environmental quality and the prevalence of childhood asthma and rhinitis in Wuhan area of China

Indoor environmental quality is suspected to be at least part of the cause of the increasing prevalence of childhood asthma and allergy. This study is part of the China, Children, Homes, Health (CCHH) project, which was designed to identify the risk factors indoors that are associated with prevalence of asthma and allergy among children in China. A cross-sectional questionnaire study was carried out in Wuhan in 2011. The questionnaire was a modified (to Chinese building characteristics) version of a questionnaire used first in Sweden. The parents of 2193 children, aged 1–8 years, replied, a response rate of 91.4% (2193/2400). Prevalences of asthma and allergic symptoms were calculated, and a Chi-square test and multiple logistic regression were used to identify risk factors. Prevalences of health outcomes are “wheezing last 12 months” 18.5%, “cough at night last 12 months” 15.4%, “doctor-diagnosed asthma” 6.0%, “rhinitis last 12 months” 48.7%, “doctor-diagnosed allergic rhinitis” 17.5%. Factors associated with increased risk for asthma, allergy and related symptoms include living in an urban area, dampness (significant), use of gas for cooking, new dwelling decoration (paint and furniture obtained during pregnancy), keeping pets and breast feeding less than 3 months. Factors associated with reduced risk as installing an exhaust fan in the bathroom. Home environmental factors are significantly associated with the prevalence of childhood asthma and rhinitis in Wuhan. Urbanization and dampness problems at home are significant risk factors for doctor diagnosed asthma and allergic rhinitis among children in Wuhan.     

Structures of complement component C3 provide insights into the function and evolution of immunity

The mammalian complement system is a phylogenetically ancient cascade system that has a major role in innate and adaptive immunity. Activation of component C3 (1,641 residues) is central to the three complement pathways and results in inflammation and elimination of self and non-self targets. Here we present crystal structures of native C3 and its final major proteolytic fragment C3c. The structures reveal thirteen domains, nine of which were unpredicted, and suggest that the proteins of the alpha2-macroglobulin family evolved from a core of eight homologous domains. A double mechanism prevents hydrolysis of the thioester group, essential for covalent attachment of activated C3 to target surfaces. Marked conformational changes in the alpha-chain, including movement of a critical interaction site through a ring formed by the domains of the beta-chain, indicate an unprecedented, conformation-dependent mechanism of activation, regulation and biological function of C3.     

Low variability in a Y-linked plant gene and its implications for Y-chromosome evolution

Sex chromosomes have evolved independently in several different groups of organisms, but they share common features, including genetic degeneration of the Y chromosome. Suppression of recombination between ancestral proto-X and proto-Y chromosomes is thought to have led to their gradual divergence, and to degeneration of the Y chromosome, but the evolutionary forces responsible are unknown. In non-recombining Y chromosomes, deleterious mutations may be carried to fixation by linked advantageous mutations ("selective sweeps"). Occurrence of deleterious mutations may drive "Muller's ratchet" (stochastic loss of chromosomes with the fewest mutations). Selective elimination of deleterious mutations, causing "background selection" may accelerate stochastic fixation of mildly detrimental mutations. All these processes lower effective population sizes, and therefore reduce variability of genes in evolving Y chromosomes. We have studied DNA diversity and divergence in a recently described X- and Y-linked gene pair (SLX-1 and SLY-1) of the plant Silene latifolia to obtain evidence about the early stages of Y degeneration. Here we show that DNA polymorphism in SLY-1 is 20-fold lower than in SLX-1, but the pattern of polymorphism does not suggest a selective sweep.     

植物天然免疫系统研究进展

很多植物病原菌严重地损害植物的生长和繁殖。植物与病原体协同进化过程中,也逐渐形成了一系列复杂高效的保护机制来抵御病原物的侵染。植物中抵抗外界微生物刺激所形成的系统被称为植物天然免疫系统,可分为两个层次。第1个层次是植物模式识别受体(PRRs)识别病原相关分子模式(PAMPs),触发病原相关分子模式触发的免疫反应（PTI）,激活植物体中促丝裂原活化蛋白激酶(MAPK)信号通路使植物产生早期应答反应。PTI适应性较广,可识别和响应包括非致病菌的许多类微生物。第2个层次是病原菌产生效应因子抑制基础免疫响应PTI,而植物产生针对性更强的抗性蛋白(R蛋白)识别效应因子,并通过效应因子触发型免疫(ETI)来重建植物的抗性。笔者综述了近年来植物天然免疫系统的研究进展,认为随着对植物天然免疫系统研究的深入,应重视PTI和ETI的结合利用,有效扩大植物抗菌谱,改良植物ETI抗性。     

A role for the C3a anaphylatoxin receptor in the effector phase of asthma

Asthma is a chronic inflammatory disease of the airways and lung mucosa with a strong correlation to atopy and acquired (IgE) immunity. However, many features of bronchial asthma, such as smooth muscle contraction, mucus secretion and recruitment of inflammatory cells, are consistent with the actions of complement anaphylatoxins, in particular C3a and C5a. Complement activation forms a central core of innate immune defence against mucosal bacteria, viruses, fungi, helminths and other pathogens. As a system of 'pattern-recognition molecules', foreign surface antigens and immune complexes lead to a proteolytic cascade culminating in a lytic membrane attack. The anaphylatoxins C3a and C5a are liberated as activation byproducts and are potent pro-inflammatory mediators that bind to specific cell surface receptors and cause leukocyte activation, smooth muscle contraction and vascular permeability. Here we show that in a murine model of allergic airway disease, genetic deletion of the C3a receptor protects against the changes in lung physiology seen after allergen challenge. Furthermore, human asthmatics develop significant levels of ligand C3a following intra-pulmonary deposition of allergen, but not saline. We propose that, in addition to acquired immune responses, the innate immune system and complement (C3a in particular) are involved in the pathogenesis of asthma.     

Activation in vitro of sequence-specific DNA binding by a human regulatory factor

The human heat-shock factor (HSF) regulates heat-shock genes in response to elevated temperature. When human cells are heated to 43 degrees C, HSF is modified post-translationally from a form that does not bind DNA to a form that binds to a specific sequence (the heat-shock element, HSE) found upstream of heat-shock genes. To investigate the transduction of the heat signal to HSF, and more generally, how mammalian cells respond at the molecular level to environmental stimuli, we have developed a cell-free system that exhibits heat-induced activation of human HSF in vitro. Comparison of HSF activation in vitro and in intact cells suggests that the response of human cells to heat shock involves at least two steps. First, an ATP-independent, heat-induced alteration of HSF allows it to bind the HSE; the temperature at which activation occurs in vitro implies that a human factor directly senses temperature. Second, HSF is phosphorylated. It is possible that similar multi-step activation mechanisms play a role in the response of eukaryotic cells to a variety of environmental stimuli, and that these mechanisms evolved to increase the range and flexibility of the response.     

酶催化功能混杂性研究进展

酶催化生物体内化学反应,是生命代谢形成运转的动力。与传统观点认为酶具有专一性催化功能相对,近年来生物信息与实验分析都证实了酶具有多种混杂催化功能是普遍存在的现象。在过去的几十亿年里,古老酶一直不断演化以适应变化的环境,形成现代功能多样的酶蛋白家族。基于独特底物结合模式和动态蛋白结构的催化功能混杂性是酶蛋白适应性演化的基础。酶的混杂活性有望被开发应用于药物酶法合成及环境修复领域。本文就酶催化功能混杂性的普遍性、分子机理、可进化性等方面的相关研究进展进行综述。