The development and role of microbialhost interactions in gut mucosal immune development

At birth the piglet's immune system is immature and it is dependent upon passive maternal protection until weaning.The piglet's mucosal immune system develops over the first few weeks but has not reached maturity at weaning ages which are common on commercial farms. At weaning piglets are presented with a vast and diverse range of microbial and dietary/environmental antigens. Their ability to distinguish between antigens and mount a protective response to potential pathogens and to develop tolerance to dietary antigens is critical to their survival and failure to do so is reflected in the high incidence of morbidity and mortality in the post-weaning period. A growing recognition that the widespread use of antibiotics to control infection during this critical period should be controlled has led to detailed studies of those factors which drive the development of the mucosal immune system, the role of gut microbiota in driving this process, the origin of the bacteria that colonise the young piglet's intestine and the impact of rearing environment. This review briefly describes how the mucosal immune system is equipped to respond "appropriately" to antigenic challenge and the programmed sequence by which it develops. The results of studies on the critical interplay between the host immune system and gut microbiota are discussed along with the effects of rearing environment. By comparing these with results from human studies on the development of allergies in children, an approach to promote an earlier maturation of the piglet immune system to resist the challenges of weaning are outlined.     

The immune modifying effects of amino acids on gut-associated lymphoid tissue

The intestine and the gut-associated lymphoid tissue (GALT) are essential components of whole body immune defense, protecting the body from foreign antigens and pathogens, while allowing tolerance to commensal bacteria and dietary antigens. The requirement for protein to support the immune system is well established. Less is known regarding the immune modifying properties of individual amino acids, particularly on the GALT. Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake, but the availability of specific dietary amino acids (in particular glutamine, glutamate, and arginine, and perhaps methionine, cysteine and threonine) are essential to optimizing the immune functions of the intestine and the proximal resident immune cells. These amino acids each have unique properties that include, maintaining the integrity, growth and function of the intestine, as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers, specific T cell functions, and the secretion of IgA by lamina propria cells. Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters. Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.     

Immune responses to dietary antigens in gluten-sensitive enteropathy of Irish setters

This study examined whether increased intestinal permeability in Irish setters with gluten-sensitive enteropathy was associated with altered immune responses to ingested antigens, and whether a humoral immune response to gluten is involved in the pathogenesis of the condition. Affected setters reared on a wheat-containing diet were compared with littermates reared on a cereal-free diet and age-matched control setters. Measurement of serum immunoglobulins revealed increased serum IgA concentrations in affected dogs. Antibody responses to a variety of dietary antigens were measured by elisa. Antibody levels to ovalbumin, collagen I and II and soya were not significantly different from normal dogs. Anti-gliadin antibody concentrations were lower in affected dogs than controls, and correlated with immune complex formation as assessed by CIq binding. The study suggested a modified immune response in dogs with increased intestinal permeability, although there was no major systemic antibody response to dietary antigens.     

Effect of dietary xylitol on growth and inflammatory responses in immune stimulated chickens

It has been argued that stimulation of the immune system depresses performance. Accordingly, an experiment was conducted to determine the effect of dietary xylitol (150 g/kg diet) on growth and selected inflammatory responses in male broiler chickens. During the final 6 d of the experimental periods, chicks were injected with antigens: Escherichia coli lipopolysaccharide (LPS) on days 1, 3 and 5 and with Sephadex-G50 superfine on days 2 and 4 to stimulate macrophage functions. The immune stimulation reduced body weight gain and food intake, but enhanced alpha 1 acid glycoprotein (AGP) concentration and interleukin (IL-1) like activity in plasma. Feeding the xylitol diet partially, but significantly, prevented the reductions in body weight gain and food intake, without affecting the early stage of inflammatory responses triggered by LPS and Sephadex injections.     

Oral immunisation of pigs with fimbrial antigens of enterotoxigenic E. coli: an interesting model to study mucosal immune mechanisms

The intestinal mucosal immune system can discriminate actively between harmful pathogenic agents and harmless food antigens resulting in different immune responses namely IgA production and oral tolerance, respectively. Recently, a pig model has been developed for studying intestinal mucosal immune responses in which F4 fimbrial antigens of enterotoxigenic Escherichia coli (F4 ETEC) are used as oral antigens. A unique feature of this model is that soluble F4 antigens can be administered to pigs which have a receptor for this fimbriae (F4R(+)) on their small intestinal villous enterocytes and pigs which do not have this receptor (F4R(-)). Oral administration of F4 to the F4R(+) pigs results in an intestinal mucosal immune response that completely protects the pigs against a challenge infection. In F4R(-) pigs such an intestinal mucosal immune response does not occur. However, a priming of the systemic immune system can be seen similar to the priming in pigs fed with the same dose of a food antigen, suggesting that F4 in F4R(-) pigs behaves as a food antigen. The fact that different mucosal immune responses can be induced with soluble F4, makes it an interesting model to study mucosal immune mechanisms in the pig.     

Immunogenetics and the major histocompatibility complex.

The poultry immune system is a complex system involving many different cell types and soluble factors that must act in concert to give rise to an effective response to pathogenic challenge. The complexity of the immune system allows the opportunity for genetic regulation at many different levels. Cellular communication in the immune response, the production of soluble factors, and the rate of development of immune competency are all subject to genetic influences. The genes of the major histocompatibility complex (MHC) encode proteins which have a crucial role in the functioning of the immune system. The MHC antigens of chickens are cell surface glycoproteins of three different classes: Class I (B-F), Class II (B-L) and Class IV (B-G). The MHC antigens serve as essential elements in the regulation of cell-cell interactions. The MHC has been shown to influence immune response and resistance to autoimmune, viral, bacterial and parasitic disease in chickens. The MHC has been the primary set of genes identified with genetic control of immune response and disease resistance, but there are many lesser-characterized genes outside of the MHC that also regulate immunoresponsiveness. Polygenic control has been identified in selection experiments that have produced lines of chickens differing in antibody levels or kinetics of antibody production. These lines also differ in immunoresponsiveness and resistance to a variety of diseases. Understanding the genetic bases for differences in immunoresponsiveness allows the opportunity selectively to breed birds which are more resistant to disease. Indirect markers that can be used for this selection can include the MHC genes and immune response traits that have been associated with specific or general resistance to disease.     

Sensitisation of preruminant calves and piglets to antigenic protein in early weaning diets: control of the systemic antibody responses

The immune response stimulated by dietary protein was studied in preruminant calves and piglets. Calves receiving dietary soya developed high serum titres of soya-specific IgG which did not decline with prolonged feeding. IgG1 and IgG2 subclasses showed a parallel rise although IgG1 predominated. Levels of antibody evoked by a combination of oral and parenteral sensitisation with soya protein were significantly greater than by parenteral sensitisation alone. These results suggest that the calves failed to develop oral tolerance. Passively acquired maternal soya-specific antibody did not influence the response to oral or parenteral sensitisation with soya. By contrast, piglets weaned onto a soya-containing diet became hyporesponsive to injection with soya protein. Thus, calves and piglets appear to differ in their ability to control adverse immune responses to dietary antigens. This could influence the severity of gastrointestinal disorders associated with early weaning diets.     

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.     

Immunoprophylaxis of bovine dermatophytosis.

The literature on immunoprophylaxis as control method for ringworm in cattle is reviewed. Scientific papers on immune response to dermatophyte antigens and vaccination against ringworm were obtained from personal files and computerized search in 4 relevant databases. Vaccines with antigens of Trichophyton verrucosum stimulate a humoral and cellular immune response. In animals vaccinated with inactivated vaccines, some protection is observed after challenge. However, the protective immunity is inadequate in most cases. Vaccination with live vaccines elicits an immune response that prevents the development of clinical disease. The protective immunity is based mainly on the cellular branch of the immune system. The efficacy and safety of live dermatophyte vaccines have been demonstrated in both challenge experiments and field trials from different countries. Effective control of ringworm in cattle has been achieved in regions implementing systematic vaccination.     

Plant-made vaccines: biotechnology and immunology in animal health

The use of plants as production systems for vaccine antigens has been actively investigated over the last 15 years. The original research focused on the value of this expression system for oral delivery based on the hypothesis that plant-expressed antigens would be more stable within the digestive tract and would allow for the use of the oral route of administration to stimulate a mucosal immune response. However, while first conceived for utility via the oral route, plant-made antigens have also been studied as classical immunogens delivered via a needle to model animal systems. Antigens have been expressed in a number of whole plant and cell culture systems. Several alternative expression platforms have been developed to increase expression of antigens or to elicit preferred immunological responses. The biotechnological advances in plant expression and the immunological testing of these antigens will be reviewed in this paper focusing primarily on diseases of livestock and companion animals.     

Sequential bacteriological observations in relation to cell-mediated and humoral antibody responses of cattle infected with Mycobacterium paratuberculosis and maintained on normal or high iron intake

Twenty calves were orally infected with Mycobacterium paratuberculosis before weaning. Ten of these plus 4 non-infected controls were maintained on elevated dietary iron intake from 6 to 33 months of age. During this time, in which the majority of animals were bred, the influence of increased dietary iron upon tests of cellular and humoral immune responsiveness to antigens of the organism were monitored. Results were examined in relation to the organism's capacity to multiply and infect up to 7 portions of the intestinal tract. No significant differences were detected in the degree of intestinal disease or pattern of faecal excretion of M. paratuberculosis in iron supplemented and non-supplemented cattle. Cutaneous delayed-type hypersensitivity (DTH) to johnin PPD developed at 1 month and in-vitro lymphocyte and immunostimulatory activity (LS) to this antigen at 2 months after infection. LS indices were significantly reduced in magnitude in iron-supplemented cattle (p less than 0.01). Most ELISA antibody responses were positive 10 to 17 months after infection and preceded the fewer number of CF responses by several months. Neither of the antibody tests was affected by elevated iron intake. Generally, complete or partial resistance to paratuberculosis was associated with sustained positive monthly LS tests (index greater than or equal to 2.0), whereas antibody levels tended to be sustained only in the more severely affected cattle. Although neither test system was affected by pregnancy the ELISA failed to detect a significant proportion of cattle chronically shedding M. paratuberculosis in faeces.     

血吸虫的抗原伪装研究进展

抗原伪装是包括寄生虫在内的病原体的一种逃避宿主免疫反应方式.血吸虫在宿主间的转移实验证明了血吸虫具有抗原伪装现象.在血吸虫生活史的主要阶段均发现了许多与宿主相同的抗原以及众多的免疫抑制物质.这些物质有些是血吸虫自身表达的,有些是血吸虫结合的宿主抗原.它们通过掩盖血吸虫抗原等多种机理伪装血吸虫进而使血吸虫逃避宿主的免疫攻击.     

黏膜免疫佐剂的研究进展

黏膜免疫在机体抵抗病原入侵时发挥着重要的作用，疫苗通过黏膜免疫可以引起局部和全身的免疫应答。但是疫苗经过消化道黏膜时常受到消化液的降解，而且常常会引起免疫耐受，为了克服这些困难，人们设计了大量的黏膜免疫佐剂以增强机体对抗原的黏膜免疫力和全身的免疫应答水平。作者就近年来黏膜免疫佐剂的研究进展作一综述。     

Trichinella antigens: a review

This paper presents a review of the Trichinella antigens within the context of species variation. As with other parasites, Trichinella antigens can be classified according to their localisation as surface, excretory/secretory (ES) and somatic components. Surface antigens are mainly constituents of the outer cuticle although secretions from inner parts of the body wall as well as from the oesophagus can temporarily accumulate in the surface. ES antigens come mainly from the excretory granules of the stichosome, whereas somatic constitutive antigens come from the internal parts of the worms. ES products are considered very important from an immunological point of view as they are easily targeted by the immune system, whereas parasite death is required for exposure of somatic products. Some of the antigenic components have been characterised chemically. Phosphorylcholine is an important hapten that modulates the immune responses in Trichinella infections. Glycoproteins are the major components of surface and excretory/secretory products. A 43-kDa glycoprotein has been regarded as a good candidate for diagnosis and vaccination purposes. Recently some glycans have received special attention either as relevant epitopes or as parasite evasion strategies.     

The evaluation of an experimental porcine herpesvirus 1 (Aujeszky's disease virus) subunit vaccine in mice

Porcine herpesvirus 1 (PHV-1) antigens were extracted from virus-infected cells using the nonionic detergent Triton X-100. A single vaccination with these viral antigens in Freund's incomplete adjuvant resulted in the production of neutralizing antibody and a cellular immune response in mice. An 87% rate of protection was observed in these mice upon challenge with a lethal dose of PHV-1. A second vaccination given at day 21 resulted in higher levels of neutrilizing antibody and 100% protection of vaccinated mice upon challenge with virulent PHV-1.     

Circulating lymphocytes, neutrophils and immune complexes in pigs after feeding

There are reports in the literature claiming that pigs experience a lymphopenia after feeding. This is not observed in other species. We set out to investigate this phenomenon because of the unusual route of lymphocyte recirculation in pigs. for it suggested that this might be a specific response to dietary antigens. We were unable to confirm this phenomenon. A lymphopenia was observed in both test and control groups as a non-specific response to restraint and blood sampling. In contrast, feeding was associated with a significant neutrophilia (mean 58%, P less than 0.002). There were no increases in circulating IgA, IgG or IgM immune complexes after feeding but IgG immune complexes remained at a higher level than in the control group.     

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.     

Mucosal immunology: overview and potential in the veterinary species

A large part of the immune system is dedicated to protection from infection at mucosal surfaces. The concept of the common mucosal immune system has been investigated in several veterinary species where traffic of mucosally activated lymphocytes from induction to effector sites has been demonstrated. The dominant isotype found in secretions of the upper respiratory tract and gut of normal healthy and diseased animals is IgA. B lymphocytes have a relatively short half-life and there is continuous production of IgA at these sites, which is achieved by constant secretion from T helper and epithelial cells of cytokines that are critical for B cell maturation and IgA secretion. Specific stimulation of mucosal immune responses using intranasal presentation of live and inactivated antigens (with adjuvants active at mucosal surfaces) has shown great promise for inducing protective immunity to respiratory pathogens.     

Overview of new vaccines and technologies

Molecular technology has given us a greater insight into the aetiology of disease, the functioning of the immune system and the mode of action of veterinary pathogens. The knowledge gained has been used to develop new vaccines with specific, reactive antigens which elicit protective immune mediated responses (humoral and/or cell mediated) in the host. These vaccines should not burden the immune system by initiating responses against non-essential antigens. However, the efficacy of these vaccines is only as good as the delivery technology or route used to present them to the immune system. Some vaccines, traditionally given by the parenteral route, are now given by the natural route; either orally or intranasally. Two major advantages, often interrelated, are the rapid onset of immunity and stimulation of the local, mucosal immunity. These new technologies are now making an impact on current vaccine development. The balance has to be found between what is technologically feasible and what will provide at least as good a protective immunity as current, conventional vaccines. As new and emerging diseases appear globally, new opportunities arise for molecular and conventional technologies to be applied to both the development and delivery of novel vaccines, as well as the improvement of vaccines in current use.     

Dietary fiber and microbiota interaction regulates sow metabolism and reproductive performance

Dietary fiber is a critical nutrient in sow diet and has attracted interest of animal nutritionists for many years. In addition to increase sows’ satiety, dietary fiber has been found to involve in the regulation of multiple biological functions in the sow production. The interaction of dietary fiber and gut microbes can produce bioactive metabolites, which are of great significance to sows'' metabolism and reproductive performance. This article reviewed the interaction between dietary fiber and gut microbes in regulating sows'' gut microbial diversity, intestinal immune system, lactation, and production performance, with the aim to provide a new strategy for the use of dietary fiber in sow diets.