The postnatal development of the mucosal immune system and mucosal tolerance in domestic animals

The mucosal immune system is exposed to a range of antigens associated with pathogens, to which it must mount active immune responses. However, it is also exposed to a large number of harmless antigens associated with food and with commensal microbial flora, to which expression of active, inflammatory immune responses to these antigens is undesirable. The mucosal immune system must contain machinery capable of evaluating the antigens to which it is exposed and mounting appropriate effector or regulatory responses. Since the immune system is likely to have evolved initially in mucosal tissues, the requirement to prevent damaging allergic responses must be at least as old as the adaptive immune system, and studies of the mechanisms should include a range of non-mammalian species. Despite the importance for rational design of vaccines and for control of allergic reactions, the mechanisms involved are still largely unclear. It is not clear that the classical experimental protocol of "oral tolerance" is, in fact, measuring a biologically important phenomenon, nor is it clear whether tolerance is regulated in the evolutionarily recent organised lymphoid tissue (the lymph nodes) or the more ancient, diffuse architecture in the intestine. The capacity of the immune system to discriminate between "dangerous" and "harmless" antigens appears to develop with age and exposure to microbial flora. Thus, the ability of an individual or a group of animals to correctly regulate mucosal immune responses will depend on age, genetics and on their microbial environment and history. Attempts to manipulate the mucosal immune system towards active immune responses by oral vaccines, or towards oral tolerance, are likely to be confounded by environmentally-induced variability between individuals and between groups of animals.     

Gut health:The results of microbial and mucosal immune interactions in pigs

There are a large number of microorganisms in the porcine intestinal tract. These microorganisms and their metabolites contribute to intestinal mucosal immunity, which is of great importance to the health of the host. The host immune system can regulate the distribution and composition of intestinal microorganisms and regulate the homeostasis of intestinal flora by secreting a variety of immune effector factors, such as mucin, secretory immunoglobulin A (sIgA), regenerating islet-derived III (RegIII)γ, and defensin. Conversely, intestinal microorganisms can also promote the differentiation of immune cells including regulatory T cells (T_reg) and Th17 cells through their specific components or metabolites. Studies have shown that imbalances in the intestinal flora can lead to bacterial translocation and compromised intestinal barrier function, affecting the health of the body. This review focuses on the composition of the pig intestinal flora and the characteristics of intestinal mucosal immunity, discusses the interaction mechanism between the flora and intestinal mucosal immunity, as well as the regulation through fecal microbiota transplantation (FMT), dietary nutritional composition, probiotics and prebiotics of pig intestinal microecology. Finally, this review provides insights into the relationship between intestinal microorganisms and the mucosal immune system.     

The influence of environment on development of the mucosal immune system

The mucosal immune system expresses active responses against pathogens and also tolerance against harmless food and commensal bacterial antigens. The mechanisms that determine which of these outcomes occur after recognition of antigens by T-cells are not clear. One possibility is that it is determined by the initial interaction between a dendritic and a na?ve T-cell in organised lymphoid tissue. However, such organised structures are, evolutionarily, quite recent and the original immune system must have made appropriate responses in more diffuse immunological architecture; a second possibility is that the critical interaction is between primed T-cells and their environment, in the lamina propria of the intestine. The mucosal immune system of neonates is poorly developed and inefficient at expressing appropriate immune responses. Development is influenced by a range of environmental factors including maternally derived antigen or antibody and commensal flora and pathogens. The intestine is a complex immunological structure in which the immune system and the macro- and microenvironment interact.     

The role of neuroendocrine immune interactions in the initiation of humoral immunity in chickens

The presence of neuroendocrine immune interaction in mammalian species has been studied extensively and has been established. However, such an interaction is not as well established in avian species. Furthermore, the role of such an interaction in the initiation of humoral immunity is not well understood. Therefore, the present studies were conducted to determine mechanisms involved in the initiation of humoral immunity in chickens. Cornell K-strain White Leghorn immature male chickens were used for all the experiments. Changes in hormonal and leukocyte profiles after antigen stimulation were studied. The ability of different leukocytes to produce ACTH was also investigated. It was concluded that the first step in the initiation of humoral immunity after antigen exposure is the release of interleukin-1 by macrophages, which in turn stimulates the production of CRF by hypothalamus and/or leukocytes. It is important to mention that CRF production could also be a direct effect of antigen stimulation. The CRF will then stimulate ACTH production by anterior pituitary and/or leukocytes. In addition, CRF will directly enhance lymphocyte activities in the spleen. Corticosteroid production will be stimulated by ACTH and will cause redistribution of lymphocytes from circulation to secondary lymphoid organs such as the spleen for antigen processing and eventual production of antibodies against the invading antigens. Finally, both ACTH and corticosteroids will later act in a negative feedback manner to regulate and control the process of antibody production by inhibiting lymphocyte activities and/or reducing the responsiveness to different stimuli.     

Manipulation of the gut microbiota in C57BL/6 mice changes glucose tolerance without affecting weight development and gut mucosal immunity

Inflammatory diseases such as type 2 diabetes (T2D) in humans and mice are under the influence of the composition of the gut microbiota (GM). It was previously demonstrated that treating Lep(ob) mice with antibiotics improved glucose tolerance. However, wild type C57BL/6J mice may also exhibit plasma glucose intolerance reminiscent of human T2D. We hypothesized that antibiotic treatment in C57BL/6 mice would have an impact on glucose tolerance without affecting weight and gut immunology. When compared to mice treated with erythromycin or the controls, treatment for five weeks with ampicillin improved glucose tolerance without significantly affecting the weight or the number of gut mucosal regulatory T cells, tolerogenic dendritic cells or T helper cells type 1. 16S rRNA gene based denaturing gradient gel electrophoresis profiles clearly clustered according to treatment and showed that antibiotic treatment reduced GM diversity. It is concluded that antibiotic treatment changes glucose metabolism as well as the composition of the GM in C57BL/6 mice, and that this does not seem to be correlated to weight development in the mice.     

动物粘膜免疫及其细胞因子

粘膜免疫系统是机体抵抗病原微生物的第一道防线,广泛分布在呼吸道、消化道、泌尿生殖道及一些外分泌腺体的淋巴组织,是执行局部特异性免疫功能的主要场所,粘膜免疫的重要功能和独特性质日益受到重视。本文主要就其抗原逞递、淋巴细胞归巢、SIgA的功能及吸入耐受、细胞因子等方面的研究概况进行综述。     

动物黏膜免疫与细胞因子的研究进展

黏膜免疫系统是机体抵抗病原微生物的第一道防线,而黏膜相关趋化性细胞因子在生理病理过程中也发挥重要作用,其对研究黏膜免疫系统的特殊功能和独特性质具有重要意义.本文概述了黏膜免疫的特点、机制、途径及与之相关的几类重要的细胞因子.     

口服黄芪多糖增强肠道黏膜免疫及其对口蹄疫疫苗免疫的影响

将40只小鼠随机分为2组,一组小鼠灌服黄芪多糖水溶液,另一组灌服生理盐水为对照组,给药后每周从各组随机取5只小鼠,分离脾淋巴细胞进行淋巴细胞增殖试验,并观察十二指肠黏膜上皮内淋巴细胞(IELs)以及上皮固有层的IgA+细胞数;将24只小鼠随机分为4组,各小鼠分2次,间隔2周注射口蹄疫(FMD)疫苗,其中1~3组的小鼠在疫苗免疫前灌服不同剂量的黄芪多糖,第4组小鼠灌服生理盐水作为对照。二免后1~5周,每周采血,检测血清IgG及其亚类。结果表明,小鼠口服黄芪多糖能显著促进小鼠淋巴细胞对刀豆蛋白A(ConA)和脂多糖(LPS)的刺激反应,并增加十二指肠IELs和固有层IgA+细胞数量;口服黄芪多糖后接种FMD疫苗,能够显著增强血清FMD特异性IgG及其亚类水平。     

胃肠道黏膜免疫与动物营养调控

黏膜免疫系统(mucosal immune system,MIS)主要指呼吸道、肠道及泌尿生殖道黏膜固有层和上皮细胞下散在的无被膜淋巴组织,以及某些带有生发中心的器官化淋巴组织,如扁桃体、小肠派氏集合淋巴结(Peyer's patches,PP)及阑尾等[1],由黏膜结合淋巴组织、致敏淋巴细胞散布途径和黏膜     

口服人参皂苷Rg1提高鸡的肠道黏膜免疫

将96只SPF母鸡随机分成4组,1,4组注射生理盐水;2,3组连续3 d肌肉注射环磷酰胺(Cy)诱导免疫抑制。3组在Cy引起免疫抑制后连续7 d每天饮水口服1 mg/kg人参皂甙Rg1,其余组只饮水。1,2,3组于给药结束后免疫传染性法氏囊病毒(IBDV)疫苗,4组不免疫。于给药前和免疫后1,2,3周计算脾脏和法氏囊指数,采血测定抗体阳性率,检测十二指肠灌洗液总sIgA和特异性sIgA含量;观察十二指肠黏膜上皮内淋巴细胞(IELs)以及IgA+细胞数。于免疫后1周提取十二指肠总RNA,检测肠组织免疫相关基因mRNA的表达。结果表明,和免疫抑制组相比,饮水口服1 mg/kg人参皂苷Rg1可提高IBDV抗体阳性率,显著增加脾脏和法氏囊指数,显著提高肠道总sIgA和特异性sIgA含量;此外,口服Rg1显著增加了十二指肠IELs和固有层IgA+细胞数量,上调了鸡十二指肠TLR4、p65、TGF-β、pIgR和CCR9基因的mRNA表达水平。     

Induction of respiratory immune responses in the chicken; implications for development of mucosal avian influenza virus vaccines

The risk and the size of an outbreak of avian influenza virus (AIV) could be restricted by vaccination of poultry. A vaccine used for rapid intervention during an AIV outbreak should be safe, highly effective after a single administration and suitable for mass application. In the case of AIV, aerosol vaccination using live virus is not desirable because of its zoonotic potential and because of the risk for virus reassortment. The rational design of novel mucosal-inactivated vaccines against AIV requires a comprehensive knowledge of the structure and function of the lung-associated immune system in birds in order to target vaccines appropriately and to design efficient mucosal adjuvants. This review addresses our current understanding of the induction of respiratory immune responses in the chicken. Furthermore, possible mucosal vaccination strategies for AIV are highlighted.     

寡糖对动物免疫功能的作用

寡糖（oligosaccharides）又称为低聚糖或寡聚糖，是由2～10个单糖单位通过糖苷键连接而成的小聚合体，介于单体单糖与高度聚合的多糖之间。寡糖是中等分子的非淀粉多糖，大分子非淀粉多糖经相应酶的不完全水解可产生寡糖。在饲料中使用适量的寡糖，可以提高动物的生产性能，改善动物的健康状况，提高免疫力，防止腹泻。大量研究表明，寡糖除能改善动物消化道微生物区系，促进消化道有益菌的生长，抑制有害微生物的繁殖外，还具有调节动物机体免疫反应，     

从山东寿光看政府在农业产业化进程中的作用

9月6～10日,笔者有幸随河南省信阳市高级人才培训班赴山东寿光进行考察学习.考察期间笔者听了有关专家的讲课,分别参观了寿光蔬菜生产基地--我国最早采用冬暖式蔬菜大棚的三元朱村及全国蔬菜批发十强市场之一的寿光蔬菜批发市场.通过考察,大家边学边思、边听边问、边看边议,开阔了眼界,学习了经验,启发了思路.     

Characterization of surface markers of bovine gut mucosal leukocytes using monoclonal antibodies

The surface phenotypes of bovine intestinal leukocytes isolated from the intraepithelium (IEL), lamina propria (LPL) and Peyer's patches (PPL) of the small intestinal mucosa of normal adult cows were determined using monoclonal antibodies (mAb) specific to adult bovine peripheral blood leukocytes (PBL). Laser flow cytometric (LFC) analysis demonstrated that IEL contained significantly (P less than 0.1 to 0.02) fewer cells (26%) expressing the pan T cell phenotype in comparison to LPL (38%) and PPL (44%). Similarly, significantly (P less than 0.01 to 0.001) lower numbers of B cells were observed among IEL (10%) compared to LPL (28%) and PPL (33%). While approximately equal numbers of B7A1+ "null" cells (10%) and DH59B+ "Ia+ monocytes/granulocytes" (16.5%) were observed among the three intestinal cell populations, IEL contained significantly (P less than 0.1 to 0.05) lower numbers (19%) of T helper (Th) cells in comparison to LPL (44%) and PPL (38%). In contrast, lymphocytes with the T cytotoxic/suppressor (Tc/s) phenotype were significantly lower (P less than 0.01 to 0.001) among LPL (14.5%) compared to IEL (25%) and PPL (23%). While the numbers of cells expressing class I major histocompatibility complex (MHC) surface antigens (H58A+) were approximately equal among LPL (79%) and PPL (87%), a significant difference (P less than 0.02) was observed between IEL (71%) and PPL. Similarly, while approximately equal numbers of cells expressing the MHC class II surface phenotype were observed among LPL (42%) and PPL (46%), IEL contained significantly (P less than 0.01) fewer (31%) MHC class II cells in comparison to PPL. Enrichment for T cells by plastic adherence and Sephadex G-10/nylon wool fractionation revealed a significant (P less than 0.01) and proportional increase in T lymphocyte subsets expressing pan T, Th and Tc/s phenotypes among the three cell populations. Similarly, enrichment for B cells by the same techniques showed a significant (P less than 0.01) and proportional increase in cells expressing the panB cell phenotype among LPL and PPL. Marked differences in cell size distribution and cell surface density were observed when the three intestinal leukocyte populations were compared by LFC using monoclonal antibodies directed at various cell surface markers. Furthermore, considerable quantitative variations of each cell surface marker were observed among the individual animals tested. The results of this study indicate that bovine IEL, which contain a high percentage of cells (greater than 30%) with no known phenotype are significantly different from LPL and PPL which are phenotypically similar cell populations.(ABSTRACT TRUNCATED AT 400 WORDS)     

The role of dendritic cells in shaping the immune response

Dendritic cells are central to the initiation of primary immune responses. They are the only antigen-presenting cell capable of stimulating naive T cells, and hence they are pivotal in the generation of adaptive immunity. Dendritic cells also interact with and influence the response of cells of the innate immune system. The manner in which dendritic cells influence the responses in cells of both the innate and adaptive immune systems has consequences for the bias of the adaptive response that mediates immunity to infection after vaccination or infection. It also provides an opportunity to intervene and to influence the response, allowing ways of developing appropriate vaccination strategies. Mouse and human studies have identified myeloid, lymphoid and plasmacytoid dendritic cells. Studies in domesticated animals with agents of specific infectious diseases have confirmed the applicability of certain of the generic models developed from mice or from in vitro studies on human cells. In vivo and ex vivo studies in cattle have demonstrated the existence of a number of subpopulations of myeloid dendritic cells. These cells differ in their ability to stimulate T cells and in the cytokines that they produce, observations clearly having important implications for the bias of the T-cell response. Dendritic cells also interact with the innate immune system, inducing responses that potentially bias the subsequent adaptive response.     

Total and relative deficiency of gut mucosal IgA in German shepherd dogs demonstrated by faecal analysis

The concentration of immunoglobulins in faecal extracts was investigated as a method of assessing the production of immunoglobulins by the gut mucosa of 137 dogs. There were significant correlations between the concentrations in faecal extracts and the concentrations produced in duodenal organ cultures. Seventy-six German shepherd dogs had significantly lower median immunoglobulin A (IgA) concentrations in their faecal extracts than 63 controls of various breeds. Sixteen of the German shepherd dogs had IgA concentrations below the 95 per cent confidence limit of the control population and six had no demonstrable faecal IgA. The faecal concentrations of immunoglobulin G and albumin were significantly higher in the German shepherd dogs than in the controls, but their immunoglobulin M concentrations were similar.     

B cell development in gut associated lymphoid tissues

B lymphocyte development can occur in a variety of anatomical sites. While typically considered to be a process that occurs in the bone marrow throughout life, it is becoming clear that gut associates sites of B cell development are critically important in many species of veterinary importance. Among these sites, the bursa of Fabricius in chickens and the ileal Peyer's patches of sheep are among the best studied. In these organs, it has become clear that many of the properties associated with B cell development in rodent and primate bone marrow do not apply. Thus while bone marrow B cell development typically involves an ongoing maturation of mature B cells from immature B lineage precursors that lack the expression of a surface immunoglobulin complex, gut associated lymphoid tissues (GALTs) may be colonized by a single wave of precursor cells during embryo development. Nonetheless, molecular analysis of the requirements for B lymphocyte development in GALTs reveals some striking parallels with requirements identified for B cell development in bone marrow. This article will discuss differences between B cell development in the bone marrow and GALTs and recent evidence emerging that yields insights into how these processes are regulated.     

The impact of probiotics on gut health via alternation of immune status of monogastric animals

The intestinal immune system is affected by various factors during its development, such as maternal antibodies, host genes, intestinal microbial composition and activity, and various stresses (such as weaning stress). Intestinal microbes may have an important impact on the development of the host immune system. Appropriate interventions such as probiotics may have a positive effect on intestinal immunity by regulating the composition and activity of intestinal microbes. Moreover, probiotics participate in the regulation of host health in many ways; for instance, by improving digestion and the absorption of nutrients, immune response, increasing the content of intestinal-beneficial microorganisms, and inhibiting intestinal-pathogenic bacteria, and they participate in regulating intestinal diseases in various ways. Probiotics are widely used as additives in livestock and the poultry industry and bring health benefits to hosts by improving intestinal microbes and growth performance, which provides more choices for promoting strong and efficient productivity.     

Heat stress-induced mucosal barrier dysfunction is potentially associated with gut microbiota dysbiosis in pigs

Heat stress(HS)can be detrimental to the gut health of swine.Many negative outcomes induced by HS are increasingly recognized as including modulation of intestinal microbiota.In turn,the intestinal microbiota is a unique ecosystem playing a critical role in mediating the host stress response.Therefore,we aimed to characterize gut microbiota of pigs’exposure to short-term HS,to explore a possible link between the intestinal microbiota and HS-related changes,including serum cytokines,oxidation status,and intestinal epithelial barrier function.Our findings showed that HS led to intestinal morphological and integrity changes(villus height,serum diamine oxidase[DAO],serum D-lactate and the relative expressions of tight junction proteins),reduction of serum cytokines(interleukin[IL]-8,IL-12,interferongamma[IFN-g]),and antioxidant activity(higher glutathione[GSH]and malondialdehyde[MDA]content,and lower superoxide dismutase[SOD]).Also,16S rRNA sequencing analysis revealed that although there was no difference in microbial a-diversity,some HS-associated composition differences were revealed in the ileum and cecum,which partly led to an imbalance in the production of short-chain fatty acids including propionate acid and valerate acid.Relevance networks revealed that HS-derived changes in bacterial genera and microbial metabolites,such as Chlamydia,Lactobacillus,Succinivibrio,Bifidobacterium,Lachnoclostridium,and propionic acid,were correlated with oxidative stress,intestinal barrier dysfunction,and inflammation in pigs.Collectively,our observations suggest that intestinal damage induced by HS is probably partly related to the gut microbiota dysbiosis,though the underlying mechanism remains to be fully elucidated.