旋毛虫感染与肠黏膜免疫应答作用的研究进展

旋毛虫病是一种常见的人兽共患寄生虫病,也是一种重要的食源性寄生虫病,严重危害着人类的健康。肠黏膜是肠道寄生虫（包括旋毛虫等）进入宿主的重要门户,即机体非特异性抗感染的第一道防线,也是宿主抵御肠道寄生虫入侵的重要固有屏障,后者发挥着固有性免疫和适应性免疫功能的作用。宿主的肠黏膜免疫应答反应决定旋毛虫与宿主相互作用和适应关系。本研究就目前国内外学者研究旋毛虫感染与宿主免疫的现状,分别从肠道黏膜组织学结构、免疫细胞、细胞因子和小肠上皮细胞4个方面,综述一下肠黏膜对旋毛虫感染的免疫应答作用,目的在于揭示宿主肠黏膜对旋毛虫感染的免疫应答机制。     

Imagining 'reactivity': allergy within the history of immunology

An allergy is commonly understood to be an overreaction of the immune system to harmless substances that are misrecognised as foreign. This concept of allergy as an abnormal, misdirected immune response-a biological fault-stems from the idea that the immune system is an inherently defensive operation designed to protect the individual through an innate capacity to discriminate between the benign and toxic, or self and nonself. However, this definition of allergy represents a radical departure from its original formulation. Literally meaning 'altered reactivity', the term was coined in 1906 by Austrian paediatrician Clemens von Pirquet, to describe the fundamentally mutable nature of the immune response. This paper argues that the conventional interpretation of allergy-as-pathology derives from specific concepts of 'organism', 'response', and 'normal' immune function that have-for over a century-governed the perception and study of immune phenomena within immunology. Through an examination of Louis Pasteur's conceptualisation of the host body/microorganism relationship, I argue that immunology is founded on a view of the organism as a discrete, autonomous entity, and on a concomitant notion of the immune response as essentially reactive. Revisiting the concept of 'altered reactivity', this paper points to the fact that allergy was initially posited as a general theory of immune responsiveness and, importantly, one that poses a significant challenge to orthodox notions of immunopathology. It suggests that Pirquet's unique view of immune responsiveness presents an account of organismic or biological identity that encapsulates, rather than reduces, its ecological complexity.     

Regulation of innate immunity by the molecular machinery of macroautophagy

Innate immune responses are the first line of defence for an organism to restrict invading pathogens. They fulfil two main functions, namely detection of the pathogen to successively alarm the appropriate components of the immune system and early inhibition of the infection to prevent demise of the infected organism before a more tailored immune response, usually mediated by the adaptive immune system, can be mounted. Autophagy and phagocytosis, modified by the autophagic core machinery, contribute to these functions by regulating pathogen detection, influencing the production of innate immune mediators and directly restricting intracellular and extracellular pathogens as an effector mechanism of innate immunity. These aspects of the involvement of mainly macroautophagy in innate immune responses will be discussed in this review.     

Immunoediting: evidence of the multifaceted role of the immune system in self-metastatic tumor growth

ABSTRACT: BACKGROUND: The role of the immune system in tumor progression has been subject to discussion for many decades. Numerous studies suggest that a low immune response might be beneficial, if not necessary, for tumor growth, and only a strong immune response can counter tumor growth and thus inhibit progression. METHODS: We implement a cellular automaton model previously described that captures the dynamical interactions between the cancer stem and non-stem cell populations of a tumor through a process of self-metastasis. By overlaying on this model the diffusion of immune reactants into the tumor from a peripheral source to target cells, we simulate the process of immune-system-induced cell kill on tumor progression. RESULTS: A low cytotoxic immune reaction continuously kills cancer cells and, although at a low rate, thereby causes the liberation of space-constrained cancer stem cells to drive self-metastatic progression and continued tumor growth. With increasing immune system strength, however, tumor growth peaks, and then eventually falls below the intrinsic tumor sizes observed without an immune response. With this increasing immune response the number and proportion of cancer stem cells monotonically increases, implicating an additional unexpected consequence, that of cancer stem cell selection, to the immune response. CONCLUSIONS: Cancer stem cells and immune cytotoxicity alone are sufficient to explain the three-step "immunoediting" concept - the modulation of tumor growth through inhibition, selection and promotion.     

SNAREing immunity: the role of SNAREs in the immune system

The trafficking of molecules and membranes within cells is a prerequisite for all aspects of cellular immune functions, including the delivery and recycling of cell-surface proteins, secretion of immune mediators, ingestion of pathogens and activation of lymphocytes. SNARE (soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptor)-family members mediate membrane fusion during all steps of trafficking, and function in almost all aspects of innate and adaptive immune responses. Here, we provide an overview of the roles of SNAREs in immune cells, offering insight into one level at which precision and tight regulation are instilled on immune responses.     

Immune complex-trapping cells in the spleen of the chicken

Summary By means of immunohistoperoxidase techniques and the use of HRP-anti-HRP complexes, follicular dendritic cells in chicken spleen can be characterized both at the light-microscopical and ultrastructural level. In contrast to findings in mammals follicular dendritic cells in chicken spleen exhibit evident acid-phosphatase activity and possess considerable numbers of primary lysosomes. After intravenous injection of immune complexes a transient immune complex-trapping occurs in the peripheral parts of the Schweigger-Seidel sheath. The immune complextrapping cells in the Schweigger-Seidel sheath and germinal centre show an identical enzyme histochemical pattern and only minor differences in ultrastructural characteristics.Shortly after intravenous injection of immune complexes and carbon particles these compounds show an identical distribution pattern; however, in the following days these distribution patterns become divergent.     

Systemic immune deviation in the brain that does not depend on the integrity of the blood-brain barrier

OVA injected into the brain of normal mice evoked a deviant immune response (brain-associated immune deviation (BRAID)) that was deficient in OVA-specific delayed-type hypersensitivity. This response was not dependent on an intact blood-brain barrier since BRAID was induced even when OVA was injected into a newly created lesion site with extensive BBB leakage. However, newly activated microglia at the injection site 2 days after ablation of the striatum correlated with the loss of BRAID. At day 4 after trauma, when activated microglia were only visible further away from the injection site, BRAID was again able to be induced. In contrast to immune deviation elicited via the eye, an intact spleen was not required for BRAID, nor was BRAID adoptively transferable with spleen cells. In contrast i.v. injection of cervical lymph node cells harvested 8 days after OVA injection into the striatum was able to transfer BRAID into naive animals. Together, these data indicate that immune privilege in the brain is actively maintained and is mediated by an immune deviation mechanism that differs from eye-derived immune deviation and arises even when the BBB is compromised.     

Pathogen responses to host immunity: the impact of time delays and memory on the evolution of virulence

Current analytical models of the mammalian immune system typically assume a specialist predator-prey relationship between invading pathogens and the active components of the immune response. However, in reality, the specific immune system is not immediately effective following invasion by a novel pathogen. First, there may be an explicit time delay between infection and immune initiation and, second, there may be a gradual build-up in immune efficacy (for instance, during the period of B-cell affinity maturation) during which the immune response develops, before reaching maximal specificity to the pathogen. Here, we use a novel theoretical approach to show that these processes, together with the presence of long-lived immune memory, decouple the immune response from current pathogen levels, greatly changing the dynamics of the pathogen-immune system interaction and the ability of the immune response to eliminate the pathogen. Furthermore, we use this model to show how distributed primary immune responses combine with immune memory to greatly affect the optimal virulence of the pathogen, potentially resulting in the evolution of highly virulent pathogens.     

Special feature for the Olympics: effects of exercise on the immune system: effects of exercise on the immune system in the elderly population

Immunosenescence is characterized by impaired cellular immune function concomitant with increased inflammatory activity. Immune dysfunction is associated with increased mortality risk in elderly people. An important part of human ageing is characterized by a decline in the ability of individuals to adapt to environmental stress. Exercise has been suggested as a prototype for studying the effects of stress factors on the cellular immune system. Studies of interactions between an acute bout of exercise and immune function may be a useful and an ethically acceptable tool to investigate cell trafficking, immune mobilization/deficiency and the acute phase response during physical stress situations in relation to human ageing. Elderly humans have a preserved ability to recruit T lymphocytes and NK cells in response to an acute bout of exercise. Physical exercise training programs do not result in major restoration of the senescent immune system in humans. However, highly conditioned elderly humans seem to have a relatively better preserved immune system, although it is not possible to conclude if this is linked to training or other lifestyle-related factors.     

Research progress on the immune mechanism of the silkworm Bombyx mori

The silkworm Bombyx mori L., representing an important economic insect and one of the best models for studying insect immunity, possesses an efficient and sophisticated innate immune system against invasive microorganisms. The innate immune system basically includes humoural immunity and cellular immunity. The humoural immunity, which functions via molecules including humoural factors, lysozymes, phenoloxidase, hemolin, lectins and, in particular, antimicrobial peptides, plays a central role in eliminating the invading pathogens. The cellular immunity is primarily carried out and mediated by plasmatocytes and granular cells of haemocytes in the haemolymph, usually followed by melanization. Additionally, apoptosis, a primary viral defence for insects lacking adaptive immunity, comprises an important part of the silkworm immune system. Currently, there is still the lack of a comprehensive and systematic understanding of the molecular mechanisms of silkworm immunity. We review the latest research progress on silkworm immune mechanisms, including phenoloxidase‐dependent melanization and apoptosis, which is conducive to improving our understanding of the silkworm immune mechanism, clarifying the relationship of various immune mechanisms, and also providing a theoretical basis and reference for the future research of insect immunity.     

Early Virus-Host Interactions Dictate the Course of a Persistent Infection

Many persistent viral infections are characterized by a hypofunctional T cell response and the upregulation of negative immune regulators. These events occur days after the initiation of infection. However, the very early host-virus interactions that determine the establishment of viral persistence remain poorly uncharacterized. Here we show that to establish persistence, LCMV must counteract an innate anti-viral immune response within eight hours after infection. While the virus triggers cytoplasmic RNA sensing pathways soon after infection, LCMV counteracts this pathway through a rapid increase in viral titers leading to a dysfunctional immune response characterized by a high cytokine and chemokine expression profile. This altered immune environment allows for viral replication in the splenic white pulp as well as infection of immune cells essential to an effective anti-viral immune response. Our findings illustrate how early events during infection critically dictate the characteristics of the immune response to infection and facilitate either virus control and clearance or persistence.     

NOD样受体在炎症反应中的调控作用

天然免疫(innate immunity)是机体免疫系统直接抵御病原体入侵的最初阶段,通过机体自身的特异性模式识别受体(pattern-recognition receptors,PRRs)来识别病原体特有的保守结构病原相关分子模式(pathogen-associated molecular patterns,PAMPs)。细胞内NOD样受体(NLRs)是胞浆型PRRs中的一个重要家族,病原体侵袭细胞可上调其表达,启动机体的免疫应答和炎症反应,在机体天然免疫应答中发挥独特的功能。最近有研究证明,NLRs的突变与一些人类免疫性疾病相关,并且在细菌感染和炎症反应的控制中起重要作用。该文将讨论NLRs在炎症疾病中的调控作用。     

Basal metabolic rate and the evolution of the adaptive immune system

Vertebrates have evolved an adaptive immune system in addition to the ancestral innate immune system. It is often assumed that a trade-off between costs and benefits of defence governs the evolution of immunological defence, but the costs and benefits specific to the adaptive immune system are poorly known. We used genetically engineered mice lacking lymphocytes (i.e. mice without adaptive, but with innate, immunity) as a model of the ancestral state in the evolution of the vertebrate immune system. To investigate if the magnitude of adaptive defence is constrained by the energetic costs of producing lymphocytes etc., we compared the basal metabolic rate of normal and lymphocyte-deficient mice. We found that lymphocyte-deficient mice had a higher basal metabolic rate than normal mice with both innate and adaptive immune defence. This suggests that the evolution of the adaptive immune system has not been constrained by energetic costs. Rather, it should have been favoured by the energy savings associated with a combination of innate and adaptive immune defence.     

Immunocompetence of Galleria mellonella: sex- and stage-specific differences and the physiological cost of mounting an immune response during metamorphosis

The antibacterial immune response of the wax moth, Galleria mellonella, was analysed by use of an inhibition zone plate assay. We demonstrated significant stage-specific differences as the immune response was most effective in the pupal, next the larval and then the adult stage. In addition, we demonstrated that an immune challenge at the onset of, or during metamorphosis does not increase nor decrease the strength of the antibacterial immune response in the subsequent developmental stage(s). These findings illustrate that induced immunity is not preserved during metamorphosis but also deny any cost to the immune system itself. However, an immune challenge does induce a significant shortening of the direct development time and affects the mass loss during metamorphosis in a sex-dependent manner: males emerged smaller whereas the mass of females was not significantly affected. These observations indicate that there are sex-specific costs to mounting an immune response during metamorphosis which affect physiological traits, implicating a trade-off between immunity and development.     

Exploring the role of the immune response in preventing antibiotic resistance

For many bacterial infections, drug resistant mutants are likely present by the time antibiotic treatment starts. Nevertheless, such infections are often successfully cleared. It is commonly assumed that this is due to the combined action of drug and immune response, the latter facilitating clearance of the resistant population. However, most studies of drug resistance emergence during antibiotic treatment focus almost exclusively on the dynamics of bacteria and the drug and neglect the contribution of immune defenses. Here, we develop and analyze several mathematical models that explicitly include an immune response. We consider different types of immune responses and investigate how each impacts the emergence of resistance. We show that an immune response that retains its strength despite a strong drug-induced decline of bacteria numbers considerably reduces the emergence of resistance, narrows the mutant selection window, and mitigates the effects of non-adherence to treatment. Additionally, we show that compared to an immune response that kills bacteria at a constant rate, one that trades reduced killing at high bacterial load for increased killing at low bacterial load is sometimes preferable. We discuss the predictions and hypotheses derived from this study and how they can be tested experimentally.     

Characterizing the glycome of the mammalian immune system

The outermost layer of all immune cells, the glycocalyx, is composed of a complex mixture of glycoproteins, glycolipids and lectins, which specifically recognize particular glycan epitopes. As the glycocalyx is the cell's primary interface with the external environment many biologically significant events can be attributed to glycan recognition. For this reason the rapidly expanding glycomics field is being increasingly recognized as an important component in our quest to better understand the functioning of the immune system. In this review, we highlight the current status of immune cell glycomics, with particular attention being paid to T- and B-lymphocytes and dendritic cells. We also describe the strategies and methodologies used to define immune cell glycomes.     

Testing the effect of individual color morphology on immune response in bush-crickets

Abstract Despite the growing interest in how an individual's immune response is correlated to morphological and ecological factors, little empirical data has been available from wild insect populations. Many insects have different color morphs and exhibit differences in immune responses. Links are expected to exist between body colors and immune function in insects, because the same biochemical precursors involved in the immune response are responsible for melanin-based color markings. In this study, I assay the immune response of two different color morphs of 377 wild-caught bush-crickets, Metrioptera roeseli, from 20 populations by measuring individual encapsulation responses to a surgically implanted nylon monofilament. There was no difference between green and brown bush-cricket morphs (low melanin vs high melanin investment in cuticula color respectively) and their ability to mount an immune response to the implant. Further study is needed on the relationship between color morphology and immune response in wild insects, and whether trade-offs occur between factors during an insect's development phase and long-term health.     

Special feature for the Olympics: effects of exercise on the immune system: exercise effects on mucosal immunity

The present review examines the effects of exercise on mucosal immunity in recreational and elite athletes and the role of mucosal immunity in respiratory illness. Habitual exercise at an intense level can cause suppression of mucosal immune parameters, while moderate exercise may have positive effects. Saliva is the most commonly used secretion for measurement of secretory antibodies in the assessment of mucosal immune status. Salivary IgA and IgM concentrations decline immediately after a bout of intense exercise, but usually recover within 24 h. Training at an intense level over many years can result in a chronic suppression of salivary immunoglobulin levels. The degree of immune suppression and the recovery rates after exercise are associated with the intensity of exercise and the duration or volume of the training. Low levels of salivary IgM and IgA, particularly the IgA1 subclass, are associated with an increased risk of respiratory illness in athletes. Monitoring mucosal immune parameters during critical periods of training provides an assessment of the upper respiratory tract illness risk status of an individual athlete. The mechanisms underlying the mucosal immune suppression are unknown.