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      The Influence of MHC and Immunoglobulins A and E on Host Resistance to Gastrointestinal Nematodes in Sheep

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          Abstract

          Gastrointestinal nematode parasites in farmed animals are of particular importance due to their effects on production. In Australia, it is estimated that the direct and indirect effects of parasite infestation cost the animal production industries hundreds of millions of dollars each year. The main factors considered by immunologists when studying gastrointestinal nematode infections are the effects the host's response has on the parasite, which immunological components are responsible for these effects, genetic factors involved in controlling immunological responses, and the interactions between these forming an interconnecting multilevel relationship. In this paper, we describe the roles of immunoglobulins, in particular IgA and IgE, and the major histocompatibility complex in resistance to gastrointestinal parasites in sheep. We also draw evidence from other animal models to support the involvement of these immune components. Finally, we examine how IgA and IgE exert their influence and how methods may be developed to manage susceptible animals.

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          Most cited references 167

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          Immune regulation by helminth parasites: cellular and molecular mechanisms.

          Immunology was founded by studying the body's response to infectious microorganisms, and yet microbial prokaryotes only tell half the story of the immune system. Eukaryotic pathogens--protozoa, helminths, fungi and ectoparasites--have all been powerful selective forces for immune evolution. Often, as with lethal protozoal parasites, the focus has been on acute infections and the inflammatory responses they evoke. Long-lived parasites such as the helminths, however, are more remarkable for their ability to downregulate host immunity, protecting themselves from elimination and minimizing severe pathology in the host.
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            DNA mismatch repair and genetic instability.

            Mismatch repair (MMR) systems play a central role in promoting genetic stability by repairing DNA replication errors, inhibiting recombination between non-identical DNA sequences and participating in responses to DNA damage. The discovery of a link between human cancer and MMR defects has led to an explosion of research on eukaryotic MMR. The key proteins in MMR are highly conserved from bacteria to mammals, and this conservation has been critical for defining the components of eukaryotic MMR systems. In eukaryotes, there are multiple homologs of the key bacterial MutS and MutL MMR proteins, and these homologs form heterodimers that have discrete roles in MMR-related processes. This review describes the genetic and biochemical approaches used to study MMR, and summarizes the diverse roles that MMR proteins play in maintaining genetic stability.
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              Interaction of antigens and antibodies at mucosal surfaces.

              Infections often involve the mucosal surfaces of the body, which form a boundary with the outside world. This review focuses on immunoglobulin A (IgA) antibodies because IgA is the principal mucosal antibody class. IgA is synthesized by local plasma cells and has a specific polymeric immunoglobulin receptor-mediated transport mechanism for entry into the secretions. By serving as an external barrier capable of inhibiting attachment of microbes to the luminal surface of the mucosal epithelial lining, IgA antibodies form the first line of immune defense. In addition to this traditional mode of extracellular antibody function, recent evidence suggests that IgA antibodies can also function in a nontraditional fashion by neutralizing viruses intracellularly, if a virus is infecting an epithelial cell through which specific IgA antibody is passing on its way to the secretions. IgA antibodies are also envisaged as providing an internal mucosal barrier beneath the mucosal lining. Antigens intercepted by IgA antibodies here can potentially be ferried through the epithelium and thereby excreted. In addition to the polymeric immunoglobulin receptor on mucosal epithelial cells, IgA antibodies can bind to receptors on a variety of leukocytes and have been shown, in some experimental systems, to be capable of activating the alternative complement pathway, making IgA antibodies potential participants in inflammatory reactions. Although the relationship of IgA antibodies to inflammation is not entirely clear, the bias presented is that IgA is basically noninflammatory, perhaps even anti-inflammatory. According to this view, the major role of the Fc portion of IgA antibodies is to transport IgA across mucosal epithelial cells and not, as in the case of the other classes of antibody, to activate secondary phenomena of the kind that contribute to inflammation. Because of IgA's key role as an initial barrier to infection, much current research in mucosal immunology is directed toward developing new vectors and adjuvants that can provide improved approaches to mucosal vaccines. Finally, because of advances in monoclonal antibody technology, topical application of antibodies to mucosal surfaces has significant potential for preventing and treating infections.
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                Author and article information

                Journal
                J Parasitol Res
                JPR
                Journal of Parasitology Research
                Hindawi Publishing Corporation
                2090-0023
                2090-0031
                2011
                12 April 2011
                : 2011
                Affiliations
                1Curtin Health Innovation Research Institute and Western Australian Biomedical Research Institute, Curtin University, Perth, WA 6845, Australia
                2Department of Animal Production and Public Health, School of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK
                Author notes

                Academic Editor: Alvin A. Gajadhar

                Article
                10.1155/2011/101848
                3092517
                21584228
                Copyright © 2011 C. Y. Lee et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Review Article

                Parasitology

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