New immunology—immunology of pattern recognition receptors

Pattern recognition receptors (PRRs) have been found on all cells of the body—cells of the innate and adaptive immune systems, epithelial and endothelial cells, keratinocytes, etc. PRRs can recognize specific molecular structures of microorganisms as well as allergens and other substances. The interaction with ligands of foreign microorganisms activates PRRs, after which host cells start to produce cytokines both to specifically activate innate immunity and to control adaptive immune reactions. On the othe hand, no immune response develops against microorganisms of the normal microflora. Practically, the development of all immune responses is controlled by PRRs. These responses start in epithelial cells, skin cells, and vascular epithelial cells, which meet alien first. The immune system uses these cells to control the composition of normal microflora. Accordingly, the definition of immune system functions should be complemented by the regulation of body’s microflora in addition to the protection from alien and altered self.     

Modulation of host immunity by beneficial microbes

In nature, plants abundantly form beneficial associations with soilborne microbes that are important for plant survival and, as such, affect plant biodiversity and ecosystem functioning. Classical examples of symbiotic microbes are mycorrhizal fungi that aid in the uptake of water and minerals, and Rhizobium bacteria that fix atmospheric nitrogen for the plant. Several other types of beneficial soilborne microbes, such as plant-growth-promoting rhizobacteria and fungi with biological control activity, can stimulate plant growth by directly suppressing deleterious soilborne pathogens or by priming aboveground plant parts for enhanced defense against foliar pathogens or insect herbivores. The establishment of beneficial associations requires mutual recognition and substantial coordination of plant and microbial responses. A growing body of evidence suggests that beneficial microbes are initially recognized as potential invaders, after which an immune response is triggered, whereas, at later stages of the interaction, mutualists are able to short-circuit plant defense responses to enable successful colonization of host roots. Here, we review our current understanding of how symbiotic and nonsymbiotic beneficial soil microbes modulate the plant immune system and discuss the role of local and systemic defense responses in establishing the delicate balance between the two partners.     

植物与病原微生物互作分子基础的研究进展

植物在与病原微生物共同进化过程中形成了复杂的免疫防卫体系。植物的先天免疫系统可大致分为两个层面。第一个层面的免疫基于细胞表面的模式识别受体对病原物相关分子模式的识别, 该免疫过程被称为病原物相关分子模式触发的免疫(PAMP-triggered immunity, PTI), 能帮助植物抵抗大部分病原微生物; 第二个层面的免疫起始于细胞内部, 主要依靠抗病基因编码的蛋白产物直接或间接识别病原微生物分泌的效应子并且激发防卫反应, 来抵抗那些能够利用效应子抑制第一层面免疫的病原微生物, 这一过程被称为效应子触发的免疫(Effector-triggered immunity, ETI)。这两个层面的免疫都是基于植物对“自我”及“非我”的识别, 依靠MAPK级联等信号网络, 将识别结果传递到细胞核内, 调控相应基因的表达, 做出适当的免疫应答。本文着重阐述了植物与病原微生物互作过程中不同层面的免疫反应所发生主要事件的分子基础及研究进展。     

Engineered metal based nanoparticles and innate immunity

Almost all people in developed countries are exposed to metal nanoparticles (MeNPs) that are used in a large number of applications including medical (for diagnostic and therapeutic purposes). Once inside the body, absorbed by inhalation, contact, ingestion and injection, MeNPs can translocate to tissues and, as any foreign substance, are likely to encounter the innate immunity system that represent a non-specific first line of defense against potential threats to the host. In this review, we will discuss the possible effects of MeNPs on various components of the innate immunity (both specific cells and barriers). Most important is that there are no reports of immune diseases induced by MeNPs exposure: we are operating in a safe area. However, in vitro assays show that MeNPs have some effects on innate immunity, the main being toxicity (both cyto- and genotoxicity) and interference with the activity of various cells through modification of membrane receptors, gene expression and cytokine production. Such effects can have both negative and positive relevant impacts on humans. On the one hand, people exposed to high levels of MeNPs, as workers of industries producing or applying MeNPs, should be monitored for possible health effects. On the other hand, understanding the modality of the effects on immune responses is essential to develop medical applications for MeNPs. Indeed, those MeNPs that are able to stimulate immune cells could be used to develop of new vaccines, promote immunity against tumors and suppress autoimmunity.     

T淋巴细胞抑制急性感染的炎症反应

炎症反应是机体针对损伤因子所产生的防御反应并伴随着红、热、肿、痛的局部临床特征.炎症反应是由多种细胞和细胞因子共同参与的复杂过程,天然免疫细胞(包括吞噬细胞、自然杀伤细胞、巨噬细胞等)是起始和推进炎症反应的重要效应细胞,而获得性免疫细胞如T细胞不仅参与后期炎症反应的发生同时还具有调节早期炎症反应的重要功能.炎症反应本身有利于清除消灭致病因子,液体的渗出可稀释毒素,吞噬搬运坏死组织以利于再生和修复,使致病因子局限在炎症部位而不致蔓延全身.另一方面,过激和长期的炎症反应又会对机体造成损伤.因此,深入研究炎症反应的机制可为治疗炎症所引起的疾病提供新的思路.     

Identification and functional analysis of antifungal immune response genes in Drosophila

Essential aspects of the innate immune response to microbial infection appear to be conserved between insects and mammals. Although signaling pathways that activate NF-kappaB during innate immune responses to various microorganisms have been studied in detail, regulatory mechanisms that control other immune responses to fungal infection require further investigation. To identify new Drosophila genes involved in antifungal immune responses, we selected genes known to be differentially regulated in SL2 cells by microbial cell wall components and tested their roles in antifungal defense using mutant flies. From 130 mutant lines, sixteen mutants exhibited increased sensitivity to fungal infection. Examination of their effects on defense against various types of bacteria and fungi revealed nine genes that are involved specifically in defense against fungal infection. All of these mutants displayed defects in phagocytosis or activation of antimicrobial peptide genes following infection. In some mutants, these immune deficiencies were attributed to defects in hemocyte development and differentiation, while other mutants showed specific defects in immune signaling required for humoral or cellular immune responses. Our results identify a new class of genes involved in antifungal immune responses in Drosophila.     

The interferons and their receptors--distribution and regulation

The interferons (IFNs) were originally described over 50 years ago, identified by their ability to confer viral resistance to cells. We now know that they are much more than just anti-viral cytokines collectively having roles in both innate and adaptive immune responses, in tumor surveillance and defense, and modulation of immune cell function. Three types of IFN have now been described, simply referred to as type I, II and III. Distinguishable by the unique receptors that they rely on for signal transduction, the three types of IFN have specific and varied roles in the maintenance of human health and defense against pathogens. In mounting an IFN-mediated immune response, the human body has developed the ability to regulate IFN-mediated signal transduction. Like all cytokines, the ability of a cell to respond to IFN is completely dependent on the presence of its cognate receptor on the surface of the target cell. Thus, one of the major mechanisms used by the human body to regulate the strength and duration of the IFN response is through regulation of receptor levels, thereby altering the cytokine-specific responsiveness of the target cell. This review will discuss the receptor system utilized by the type I IFNs and compare it with that of the type II and III IFNs, which also regulate immune responses through controlling receptor level on the cell surface.     

Insect hemocytes and their role in immunity

The innate immune system of insects is divided into humoral and cellular defense responses. Humoral defenses include antimicrobial peptides, the cascades that regulate coagulation and melanization of hemolymph, and the production of reactive intermediates of oxygen and nitrogen. Cellular defenses refer to hemocyte-mediated responses like phagocytosis and encapsulation. In this review, we discuss the cellular immune responses of insects with emphasis on studies in Lepidoptera and Diptera. Insect hemocytes originate from mesodermally derived stem cells that differentiate into specific lineages identified by morphology, function, and molecular markers. In Lepidoptera, most cellular defense responses involve granular cells and plasmatocytes, whereas in Drosophila they involve primarily plasmatocytes and lamellocytes. Insect hemocytes recognize a variety of foreign targets as well as alterations to self. Both humoral and cell surface receptors are involved in these recognition events. Once a target is recognized as foreign, hemocyte-mediated defense responses are regulated by signaling factors and effector molecules that control cell adhesion and cytotoxicity. Several lines of evidence indicate that humoral and cellular defense responses are well-coordinated with one another. Cross-talk between the immune and nervous system may also play a role in regulating inflammation-like responses in insects during infection.     

多肽类药物的研究进展

多肽在包括细胞增殖分化、免疫防御、肿瘤病变等在内的生命活动过程中起着至关重要的作用。自 1953 年首个人工合成的具有生 物活性的多肽问世至今,全球上市的多肽药物有 80 多个,有大量多肽药物进入临床研究。多肽类药物具有独特的优势：活性显著、特异性 强、毒性较弱,在体内不易产生蓄积,与其他药物的相互作用比较少。综述了目前国内外多肽药物的发展情况,希望对从事多肽类药物研 发的同行有所帮助。     

肠道病毒调控固有免疫的分子机制研究进展

肠道病毒属于小核糖核酸病毒科,包括脊髓灰质炎病毒等多种重要人类病原体,已成为全球公共卫生安全的重大威胁之一。固有免疫是机体早期抵御病毒感染的重要防线。不同肠道病毒在进化中已经具备了多种途径躲避免疫识别或诱导固有免疫系统失活。本文重点对肠道病毒调控宿主固有免疫的相关分子机制进行综述,系统整理了肠道病毒逃避干扰素依赖与干扰素非依赖的抗病毒固有免疫防御的分子特征与作用规律,为肠道病毒致病机制的探究和抗病毒药物的研发提供参考。     

植物与病原微生物互作分子基础的研究进展

植物在与病原微生物共同进化过程中形成了复杂的免疫防卫体系。植物的先天免疫系统可大致分为两个层面。第一个层面的免疫基于细胞表面的模式识别受体对病原物相关分子模式的识别,该免疫过程被称为病原物相关分子模式触发的免疫(PAMP-triggered immunity,PTI),能帮助植物抵抗大部分病原微生物;第二个层面的免疫起始于细胞内部,主要依靠抗病基因编码的蛋白产物直接或间接识别病原微生物分泌的效应子并且激发防卫反应,来抵抗那些能够利用效应子抑制第一层面免疫的病原微生物,这一过程被称为效应子触发的免疫(Effector-triggered immunity,ETI)。这两个层面的免疫都是基于植物对"自我"及"非我"的识别,依靠MAPK级联等信号网络,将识别结果传递到细胞核内,调控相应基因的表达,做出适当的免疫应答。本文着重阐述了植物与病原微生物互作过程中不同层面的免疫反应所发生主要事件的分子基础及研究进展。     

Integrated approach to immunotoxicity: electron transfer, reactive oxygen species, antioxidants, cell signaling, and receptors

As with all body organs, the immune system is subjected to attack by a variety of toxins. Serious consequences can result because the immune organs serve as a defense against infective agents. The toxins, both organic and inorganic, fall into a large variety of classes, such as metals, therapeutic drugs, industrial chemicals, pollutants, pesticides, fuels, herbicides and abused drugs. Although the mode of action is multifaceted, our focus is on electron transfer (ET), reactive oxygen species (ROS), antioxidants (AOs), cell signaling, and receptors. It is significant that the toxins or their metabolites incorporate ET functionalities capable of redox cycling with resultant generation of ROS and accompanying oxidative stress.     

Relative importance of factors affecting nestling immune response differs between junior and senior nestlings within broods of hoopoes Upupa epops

Animals should invest in the immune system to protect themselves from parasites, but the cost of immune responses may limit investment depending on resource availability. In birds' broods, senior and junior chicks in size hierarchies face different rearing conditions, and thus we predicted that factors affecting immune response should differ between them. In asynchronously hatched hoopoe Upupa epops broods, we found that the immune response of senior nestlings was not related to their body condition, but positively related to risk of parasitism (which was indirectly estimated by laying date). This suggests that their immunocompetence is not limited by access to resources, and they can differentially invest in immune response with increasing risk of parasitism. On the other hand, immune response of junior nestlings was related to their body condition, but secondarily also to risk of parasitism. Our results agree with previous studies that have found significant influence of nutritional status and risk of parasitism on nestlings immune defence, but show that the effects of these environmental factors on nestling immunocompetence differ between nestlings occupying high and low rank positions in size hierarchies. The possible influence of maternal effects on the results found is also discussed.     

Actin-related defense mechanism to reject penetration attempt by a non-pathogen is maintained in tobacco BY-2 cells

The actin cytoskeleton is a key player in defense responses during early stages of infection by fungal pathogens. To investigate molecular mechanisms of actin-related defense responses, a cultured tobacco ( Nicotiana tabacum L.) BY-2 cell system was devised. When conidia were directly deposited on BY-2 cells, neither a pathogen, Erysiphe cichoracearum, nor a non-pathogen, Erysiphe pisi, was able to form appressoria or haustoria on BY-2 cells. On the other hand, conidia of the powdery mildews formed appressoria on BY-2 cells if they were covered with a thin hydrophobic membrane of Formvar. Percentages of appressoria formation of the powdery mildews on the Formvar-covered BY-2 cells were mostly the same as those on leaf epidermal cells. The pathogen successfully penetrated through the membrane into BY-2 cells and formed haustoria, whereas penetration attempts of the non-pathogen were completely rejected by the BY-2 cells similar to attempts on leaf epidermal cells. On the other hand, when BY-2 cells were treated with actin cytoskeleton-depolymerizing agents, cytochalasins, the non-pathogen became able to penetrate and form haustoria in BY-2 cells. Simultaneously, cytochalasin inhibited callose deposition at penetration sites of the non-pathogen. These results demonstrated that the actin cytoskeleton plays an important role in defense mechanisms against fungal penetration, even in the dedifferentiated cultured cells. The newly devised Formvar-covered cultured cell system will be a useful tool for molecular dissection of signal perception and defense mechanisms of plant cells during the early stage of fungal attack.     

The mechanisms for the effects of dietary lipid modification on autoimmune diseases: the role of membrane lipid composition in antigen presenting cells.

Several mechanisms have been proposed to explain the effects of dietary lipid modification on autoimmune diseases. One of these being the modification of cell membranes which affects immune functions. In order to further define this mechanism, the author proposes that dietary lipid modification could affect antigen presentation, an immune function responsible for initiating cell-mediated immune responses in body defense or autoimmune diseases, through membrane lipid composition modification.     

Liposomes in Host Defense Mechanism: A Key Role for Macrophages

Abstract

Liposomes can be used as carriers for antigens, immunomodulators and cytotoxic drugs. Such liposomes may serve as a tool to manipulate immune and non-immune host defense mechanisms. In most cases their effects are mediated by macrophages. Macrophages seem to be involved in humoral (antibody) responses and in cytotoxic T-lymphocyte responses. They are also important in non-immune defense mechanisms against foreign invaders and altered self. Which macrophages can be influenced by the liposome encapsulated molecules depends on the administration route of the liposomes. The macrophages ingest the liposomes. Once within the cell, lysosomal phospholipases disrupt the phospholipid bilayers. In this way, encapsulated molecules are released in the cell. Such liposome delivered molecules can be processed (antigens), activate the macrophage (immunomodulators) or disturb the metabolism of the cells (cytotoxic drugs). That the latter inhibition of macrophage functions may result in immunopotentiation is explained by the fact that certain macrophages are regulating immune functions by suppression.     

Regulation of TBK1 activity by Optineurin contributes to cell cycle-dependent expression of the interferon pathway

The innate immune system has evolved to detect and neutralize viral invasions. Triggering of this defense mechanism relies on the production and secretion of soluble factors that stimulate intracellular antiviral defense mechanisms. The Tank Binding Kinase 1 (TBK1) is a serine/threonine kinase in the innate immune signaling pathways including the antiviral response and the host defense against cytosolic infection by bacteries. Given the critical roles of TBK1, important regulatory mechanisms are required to regulate its activity. Among these, Optineurin (Optn) was shown to negatively regulate the interferon response, in addition to its important role in membrane trafficking, protein secretion, autophagy and cell division. As Optn does not carry any enzymatic activity, its functions depend on its precise subcellular localization and its interaction with other proteins, especially with components of the innate immune pathway. This review highlights advances in our understanding of Optn mechanisms of action with focus on the relationships between Optn and TBK1 and their implication in host defense against pathogens. Specifically, how the antiviral immune system is controlled during the cell cycle by the Optn/TBK1 axis and the physiological consequences of this regulatory mechanism are described. This review may serve to a better understanding of the relationships between the different functions of Optn, including those related to immune responses and its associated pathologies such as primary open-angle glaucoma, amyotrophic lateral sclerosis and Paget’s disease of bone.     

The evolution of immune mechanisms

From early on in evolution, organisms have had to protect themselves from pathogens. Mechanisms for discriminating "self" from "non-self" evolved to accomplish this task, launching a long history of host-pathogen co-evolution. Evolution of mechanisms of immune defense has resulted in a variety of strategies. Even unicellular organisms have rich arsenals of mechanisms for protection, such as restriction endonucleases, antimicrobial peptides, and RNA interference.In multicellular organisms, specialized immune cells have evolved, capable of recognition, phagocytosis, and killing of foreign cells as well as removing their own cells changed by damage, senescence, infection, or cancer. Additional humoral factors, such as the complement cascade, have developed that co-operate with cellular immunity in fighting infection and maintaining homeostasis. Defensive mechanisms based on germline-encoded receptors constitute a system known as innate immunity. In jaw vertebrates, this system is supplemented with a second system, adaptive immunity, which in contrast to innate immunity is based on diversification of immune receptors and on immunological memory in each individual.Usually, each newly evolved defense mechanism did not replace the previous one, but supplemented it, resulting in a layered structure of the immune system. The immune system is not one system but rather a sophisticated network of various defensive mechanisms operating on different levels, ranging from mechanisms common for every cell in the body to specialized immune cells and responses at the level of the whole organism. Adaptive changes in pathogens have shaped the evolution of the immune system at all levels.     

短链脂肪酸在宿主能量代谢方面的调节作用

肠道菌群数量庞大,对宿主多种生理活动具有重要调节作用。现有研究发现,肠道菌群主要通过调节其产生的不同代谢产物,参与宿主物质代谢反应,改变能量代谢水平,影响机体炎症反应。在诸多代谢产物中,短链脂肪酸（醋酸盐、丙酸盐、丁酸盐等）具有重要调节作用,对机体代谢功能方面具有深远影响。本文结合国内外相关研究文献,综述了短链脂肪酸在调节机体能量代谢方面的相关研究,以期为进一步阐明其在机体能量代谢方面的作用提供科学依据。