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1.
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.  相似文献   

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A thorough understanding of the immune system, including the role of different cytokines, during inflammatory diseases in ruminants could lead to the development of new diagnostic methods and treatments. Tumour necrosis factor-alpha (TNF-alpha) is an important cytokine in the onset of the inflammatory responses. Unfortunately, the number of studies on cytokines, like TNF-alpha, in ruminants is limited due to a lack of species-specific reagents. As cytokines have remained rather conserved during evolution, cross-reactivity between animal species may occur. Therefore, the aim of the present study was to investigate 5 commercially available antibodies against human TNF-alpha for their ability to cross-react with ovine and/or bovine TNF-alpha, using a bead-based flow cytometric method. Two of the antibody clones (Mab 11 and 6401.1111) showed cross reactivity with ovine recombinant TNF-alpha in concentrations above 2.5 ng/ml. However, none of the antibodies detected TNF-alpha in bovine milk, or serum containing known concentrations of bovine TNF-alpha, as earlier determined with ELISA. The results could be due to inability of the antibodies to cross-react between species, but quenching of the signal by matrix proteins might also have lowered the response.  相似文献   

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The innate immune system is essential for host defence and is responsible for early detection of potentially pathogenic microorganisms. Upon recognition of microbes by innate immune cells, such as macrophages and dendritic cells, diverse signalling pathways are activated that combine to define inflammatory responses that direct sterilisation of the threat and/or orchestrate development of the adaptive immune response. Innate immune signalling must be carefully controlled and regulation comes in part from interactions between activating and inhibiting signalling receptors. In recent years, an increasing number of pattern recognition receptors (PRRs), including C-type lectin receptors and Toll-like receptors (TLRs), has been described that participate in innate recognition of microbes, especially through the so called pathogen-associated molecular patterns (PAMPs). Recent studies demonstrate strong interactions between signalling through these receptors. Whereas useful models to study these receptors in great detail in the murine and human system are now emerging, relatively little is known regarding these receptors in companion and farm animals. In this review, current knowledge regarding these receptors in species of veterinary relevance is summarised.  相似文献   

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Immune responses are stimulated in response to threats against health. In animals, defense against infectious agents, particularly rapidly growing viruses and bacteria, requires an immediate response to limit growth and dissemination, and then stimulation of a more prolonged, specific immunity to prevent re-infection. The process by which animals meet the dual needs of an immediate response to danger and initiation of long-term protection is substantially influenced by inflammatory cytokines produced primarily by macrophages and professional antigen presenting cells (APCs). Inflammatory cytokines mobilize the immune system in response to danger and increase the efficiency of an immune response as effectors of APC function. Here we review the evidence for the involvement of inflammatory cytokines in immune induction and as mediators of APC activity, with a particular emphasis on swine and on the induction of immunity at mucosal surfaces. The vast majority of infections occur at mucosal surfaces of the enteric, respiratory and reproductive tracts, and induction of protective immunity at these sites is particularly challenging. Induction of immunity at mucosal surfaces of the small intestine is greatly facilitated by the oral adjuvant, cholera toxin (CT). CT potentiates inflammatory cytokine and costimulatory molecule expression in macrophages, and stimulates humoral and cell-mediated immune responses both locally and systemically. These observations are consistent with the hypothesis that activation of APCs is a key step in the induction of antigen-specific immunity, and that inflammatory cytokine expression is a hallmark of activated APC function. The efficacy of vaccine adjuvants, particularly in the context of mucosal immunity, may be determined by their ability to induce a controlled inflammatory response in gut-associated lymphoid tissue, characterized by the expression of various costimulatory molecules and inflammatory cytokines. Thus, elucidation of the patterns of inflammatory cytokine expression and features of APC activation will help to facilitate the rational development of more efficacious vaccines.  相似文献   

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Biological activity of immunostimulatory CpG DNA motifs in domestic animals   总被引:15,自引:0,他引:15  
Bacterial DNA contains a much higher frequency of CpG dinucleotides than are present in mammalian DNA. Furthermore, bacterial CpG dinucleotides are often not methylated. It is thought that these two features in combination with specific flanking bases constitute a CpG motif that is recognized as a "danger" signal by the innate immune system of mammals and therefore an immune response is induced when these motifs are encountered. These immunostimulatory activities of bacterial CpG DNA can also be achieved with synthetic CpG oligodeoxynucleotides (ODN). Recognition of CpG motifs by the innate immune system requires engagement of Toll-like receptor 9 (TLR-9), which induces cell signaling and subsequently triggers a pro-inflammatory cytokine response and a predominantly Th1-type immune response. CpG ODN-induced innate and adaptive immune responses can result in protection in various mouse models of disease. Based on these observations, clinical trials are currently underway in humans to evaluate CpG ODN therapies for cancer, allergy and infectious disease. However, potential applications for immunostimulatory CpG ODN in species of veterinary importance are just being explored. In this review, we will highlight what is presently known about the immunostimulatory effects of CpG ODN in domestic animals.  相似文献   

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Summary of the animal homologue section of HLDA8   总被引:1,自引:0,他引:1  
The development of reagents against leukocyte differentiation antigens in veterinary species is delayed compared to mouse and men and therefore also the number of existing reagents for the characterisation of leukocytes derived from species with importance in veterinary medicine is restricted. Cross-reactive studies with existing well defined monoclonal antibodies directed against leukocyte differentiation antigens derived from other species are an alternative approach to enhance the panel of reagents in veterinary immunology. This study describes the activities of the animal homologue section in frame of human leukocyte differentiation antigen 8-workshop (HLDA8) were 376 monoclonal antibodies, mainly directed against human leukocytes had been tested for their reactivity with 17 different animal species including non-human primates, ruminants, swine, horse, carnivores, rabbit, guinea pig, chicken and fish. In a first round 182 mAb were selected based on there reactivity in FCM analyses with at least one species for further studies, including multi-colour FCM, and molecular analyses of the antigens. Interesting was the species-overlapping reactivity of mAb directed against distinct clusters: 11 out of 17 species reacted with CD9, 11 of 17 with CD11a, CD14 (11/17), CD18 (13/17), CD21 (7/17), CD29 (10/17), CD44 (13/17), CD45 (9/17), CD47 (10/17), CD49d (13/17), CD61 (6/17), CD86 (7/17), CD91 (5/17), and CD172a (10/17), indicating evolutionary highly conserved epitopes on these surface molecules. Our results suggest the suitability of cross-reactive mAb for the animal model studies. Moreover, these findings contribute to our understanding of the evolution of the immune system.  相似文献   

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Recent studies have begun to clarify the pathogenesis of sickness behavior. Cytokines released by macrophages, dendritic cells and mast cells act on the brain to trigger behavioral changes in infected animals. The major cytokines, interleukin-1, tumor necrosis factor alpha, and others, all act on the hypothalamus to provoke alterations in the normal homeostatic condition. These include elevated body temperature, increased sleep, and loss of appetite as well as major alterations in lipid and protein metabolism leading to significant weight loss. Some of these changes are clearly directed towards enhancing the normal immune responses. The benefits of others such as appetite loss are unclear. It is also important to recognize that other animals may recognize sickness behavior as a sign of weakness and mark the victim out for targeting by predators. As a result, some prey species may work very hard to mask their sickness, a response that serves to complicate veterinary diagnosis.  相似文献   

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Eleven monoclonal antibodies specific for ovine, bovine and human cytokines were investigated by flow cytometry for cross-reactivities with cytokines produced by peripheral blood mononuclear cells (PBMCs) from sheep, cattle, goat, swine, horse, dog, mink, rabbit and human. Four antibodies specific for IL-4, IL-8, IFN-gamma and TNF-alpha cross-reacted with cytokines from a majority of the species investigated. These antibodies can be applied to flow cytometric studies of cytokine production by PBMCs from several veterinary species. Another five antibodies specific for IL-2, IL-6, GM-CSF and IFN-gamma (two antibodies) cross-reacted weakly and with a variable number of animal species. These antibodies could in certain situations be useful in flow cytometry. In a number of cases the immunological cross-reactivities were confirmed by Western blot analyses. Overall, the results of this study will remedy some of the lack of species-specific anti-cytokine antibodies in veterinary research.  相似文献   

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The fluoroquinolones are a class of compounds that comprise a large and expanding group of synthetic antimicrobial agents. Structurally, all fluoroquinolones contain a fluorine molecule at the 6-position of the basic quinolone nucleus. Despite the basic similarity in the core structure of these molecules, their physicochemical properties, pharmacokinetic characteristics and microbial activities can vary markedly across compounds. The first of the fluoroquinolones approved for use in animals, enrofloxacin, was approved in the late 1980s. Since then, five other fluoroquinolones have been marketed for use in animals in the United States, with others currently under investigation. This review focuses on the use of fluoroquinolones within veterinary medicine, providing an overview of the structure-activity relationship of the various members of the group, the clinical uses of fluoroquinolones in veterinary medicine, their pharmacokinetics and potential interspecies differences, an overview of the current understanding of the pharmacokinetic/pharmacodynamic relationships associated with fluoroquinolones, a summary of toxicities that have been associated with this class of compounds, their use in both in human and veterinary species, mechanisms associated with the development of microbial resistance to the fluoroquinolones, and a discussion of fluoroquinolone dose optimization. Although the review contains a large body of basic research information, it is intended that the contents of this review have relevance to both the research scientist and the veterinary medical practitioner.  相似文献   

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Efficacy of DNA vaccination by different routes of immunisation in sheep   总被引:4,自引:0,他引:4  
DNA vaccination, delivered through various routes, has been used extensively in laboratory animals. Few studies have focused on veterinary species and while results obtained in laboratory animals can often be extrapolated to veterinary species this is not always the case. In this study we have compared the effect of the route of immunisation with DNA on the induction of immune responses and protection of sheep to challenge with live Corynebacterium pseudotuberculosis. Intramuscular injection of plasmid DNA encoding an inactivated form of the phospholipase D (PLD) antigen linked to CTLA4-Ig resulted in the induction of a strong memory response and sterile immunity following challenge in 45% of the animals. In contrast, gene gun delivery or subcutaneous (SC) injection of the DNA vaccine induced comparatively poor responses and insignificant levels of protection. Thus, DNA vaccine efficacy in sheep is strongly influenced by the route of vaccination. Amongst intramuscular vaccinates, protected sheep had significantly elevated IgG2 responses compared to unprotected animals, while both subgroups had equivalent IgG1 levels. This suggests that the presence of IgG2 antibodies and hence a Th1-like response, induced by the DNA vaccine gave rise to protective immunity against C. pseudotuberculosis.  相似文献   

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The challenge of PRRS immunology   总被引:4,自引:0,他引:4  
Porcine reproductive and respiratory syndrome (PRRS) is one of the most challenging subjects of research in veterinary viral immunology, and the immune response against PRRS virus (PRRSV) still is poorly understood. Infected pigs develop a strong and rapid humoral response but these initial antibodies do not confer protection and can even be harmful by mediating an antibody-dependent enhancement of disease. In contrast, development of neutralising antibodies (NAs) is delayed and generation of cell-mediated immune responses, such as PRRSV-specific interferon (IFN)-gamma secreting cells, is initially erratic. In spite of this, induction of strong and rapid NAs and IFN-gamma responses seem to be required for effective vaccination. PRRSV strongly modulates the host's immune responses. The virus inhibits key cytokines, such as IFN-alpha, and may induce regulatory cytokines, such as interleukin (IL)-10. Development of NAs seems to be impaired by the existence of a decoy epitope close to the main neutralisation epitope in glycoprotein 5. This ability to modulate the host immune response probably varies among strains or isolates. The genetic diversity of the virus is very high and it has been shown that this diversity can have serious implications for the development of vaccines, since the immunity induced by one strain may be only partial against a different strain, even within the same genotype. With this panorama, the development of newer and universally efficacious PRRSV vaccines is challenging, but the present state of knowledge allows optimism if collaborative efforts are undertaken in the scientific community.  相似文献   

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An understanding of the distributional patterns of Veterinary practitioners in New York State can assist in optimizing veterinary services and opportunities. Veterinarians have been arrayed by type of practice and location within counties and major land form regions. Relationships between the number of practitioners and human and animal populations have been examined in these areas and show the inadequacy of basing veterinary needs on human population data. In contrast, large animal numbers show a much closer correspondence to veterinary practitioners, with ranges of 3341 to 6561 animals being serviced per veterinarian in the large and mixed service fields (98% of these totals are food animals). Data on age composition and degree institution (in-state versus out-of-state) provide indications of the length of service, turnover rate and retention rate for practitioners trained in New York State. At present 60 percent of New York State practitioners received their education at Cornell and more than three quarters of the active total completed their education since 1950.  相似文献   

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Chronic inflammatory liver disease regardless of aetiology leads to failing regeneration and fibrosis, ending in cirrhosis. Both in man and in animals this worldwide health problem has no definitive cure. Chronic liver injury causes hepatic stellate cells to proliferate and differentiate into matrix-producing cells. New therapeutic options will be developed upon detailed understanding of the molecular mechanisms driving liver fibrosis. This may lead to new anti-fibrotic therapies which need to be tested in suitable models before application in the veterinary and human clinic. On the other side, to restore the failing regenerative capacity of the diseased liver cells, adult progenitor cells are of interest, as an alternative to whole organ transplantation. In order to find the most suitable large animal model it is important to recognise that the typical histopathological reaction pattern of the liver can differ between mammalian species. It is therefore imperative that specialists in veterinary internal medicine and pathology, being familiar with the diseases and pathologies of the liver in different animal species, are teaming-up in finding the best models for veterinary and human liver diseases. Several large animal models have been mentioned, like pigs, sheep, and dogs. Based on the observations that man and dog share the same hepatopathies and have identical clinical, pathological and pathogenetic reaction patterns during the development of liver disease, the dog seems to be a properly suited species to test new therapeutic strategies for pets and their best friends.  相似文献   

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Pathogens that enter the body via mucosal surfaces face unique defense mechanisms that combine the innate barrier provided by the mucus layer with an adaptive response typified by the production and transepithelial secretion of pathogen-specific IgA. Both the measurement and induction of mucosal responses pose significant challenges for experimental and practical application and may need to be adapted to the species under study. In particular, for livestock, immunization procedures developed in small rodent models are not always effective in large animals or compatible with management practices. This paper reviews the latest advances in our understanding of the processes that lead to secretory IgA responses and how this relates to the development of mucosal immunization procedures and adjuvants for veterinary vaccines. In addition, it highlights the complex interactions that can take place between the pathogen and the host's immune response, with specific reference to Chlamydia/Chlamydophila infections in sheep.  相似文献   

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