Immune Recognition of Parasite Glycans
Glycan antigens have a long and detailed history in parasite immunology, dating back to identification of an allergenic polysaccharide from the nematode roundworm Ascaris by Campbell in 1936 (Campbell 1936). In the intervening 75 years, an extraordinary a
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Immune Recognition of Parasite Glycans Rick M. Maizels and James P. Hewitson
7.1
Introduction
Glycan antigens have a long and detailed history in parasite immunology, dating back to identification of an allergenic polysaccharide from the nematode roundworm Ascaris by Campbell in 1936 (Campbell 1936). In the intervening 75 years, an extraordinary array of carbohydrate structures have emerged from both of the major biological groups of parasite, the unicellular protozoa and the multicellular (metazoan) helminth worms. Parasite glycans are represented in a full range of carrier molecules, including glycoproteins through O- and N-linkages, unusual glycolipid structures, and polysaccharides. Many of the glycan determinants are novel and unique moieties, readily recognised as foreign by host antibodies, and which can dominate the antigenic profile of the parasite as a result. Importantly, protective immunity is not necessarily conferred by antibodies to immunodominant glycan epitopes, suggesting that in some cases they represent decoy specificities that distract the immune system. In addition, there are also many parasite glycans, particularly where core structures are not greatly modified, which replicate host carbohydrates. These may represent instances of molecular mimicry, allowing parasites to escape antibody targeting, or even “glycan gimmickry” in which parasites produce glycan ligands of host lectin receptors that may dampen immune responsiveness (van Die and Cummings 2010).
A chapter contributed to: Anticarbohydrate Antibodies – from Molecular Basis to Clinical Applications Editor : Paul Kosma; Pub : Springer New York Vienna, 2011 R.M. Maizels (*) • J.P. Hewitson Institute of Immunology and Infection Research, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK e-mail: [email protected] P. Kosma and S. M€uller-Loennies (eds.), Anticarbohydrate Antibodies, DOI 10.1007/978-3-7091-0870-3_7, # Springer-Verlag/Wien 2012
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R.M. Maizels and J.P. Hewitson
In this chapter, we will review the major immunogenic parasite glycans, and summarise the studies available on the specificity and nature of anti-carbohydrate antibodies in the principal parasite infections. Earlier work, much of which is still instructive, measured responsiveness to global glycan compartments, but more recent studies have resulted in fully-defined glycan structures with corresponding specific monoclonal antibodies. An important aspect is the degree to which isotype switching (e.g. from IgM to IgG) occurs in anti-carbohydrate responses, because the absence of switching may indicate a deficiency in B–T lymphocyte collaboration, and result in poor functional characteristics of the antibody. Immunity, in its broadest sense, also involves the recognition of parasite glycans to other immune system receptors (van Die and Cummings 2010), in particular innate pathogen pattern recognition receptors (PRRs), such as toll-like receptors (TLR), and in the case of glycans, C-type lectin receptors (CTL) and galectins (Robinson et al. 20
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