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			Innate immunity and autoimmunity
			Dr Robert B Sim BSc DPhil MRC Senior Scientific Staff MRC Immunochemistry Unit Phone +44 (0)1865 275351 Fax +44 (0)1865 275729 E-mail bob.sim@bioch.ox.ac.uk
Last checked: 10.01.2007 Last update: 10.01.2007
					Key publications Clark SJ et al. (2006)  His-384 allotypic variant of factor H associated with age-related macular degeneration has different heparin binding properties from the non-disease-associated form. J Biol chem. 281, 24713-20 Schneider MC et al (2006)  Functional significance of factor H binding to Neisseria meningitidis.   J Immunol. 176, 7566-75 Lillegard JB et al (2006). Recognition of Candida albicans by mannan-binding lectin in vitro and in vivo. J Infect Dis. 193, 1589-97 Arnold JN et al (2006)  Interaction of mannan binding lectin with alpha2 macroglobulin via exposed oligomannose glycans: a conserved feature of the thiol ester protein family? J Biol Chem. 281, 6955-63 Salvador-Morales C et al (2006) Complement activation and protein adsorption by carbon nanotubes. Mol Immunol. 43, 193-201 Mayilyan KR et al (2006) Heterogeneity of MBL-MASP complexes. Mol Immunol. 43, 1286-92 Rooijakkers SH et al (2005) Immune evasion by staphylococcal complement inhibitor that acts on C3 convertases. Nat Immunol. 6, 920-7
	Animals defend themselves against microorganisms by a range of mechanisms. Proteins of the innate immune system are capable of recognising and binding to many microorganisms. The major proteins of innate immunity are the Complement system proteins, and the Collectins, which are found in body fluids and tissues. Complement proteins recognise and bind to bacteria, viruses, fungi and to breakdown products of host cells. Recognition occurs by interactions with charged and uncharged regions of the target surface. Once complement proteins bind, the system is activated, and a protein called C3b is deposited on the target surface. C3b and its derivatives are recognised by receptors on phagocytes, which destroy the target. Complement proteins can also directly kill microorganisms. Complement system proteins may attack the host’s own tissues, causing inflammation and tissue damage. Such damage is particularly associated with rheumatoid diseases, forms of kidney malfunction, and transplant rejection. The system has many regulatory proteins, which act to prevent excessive activation. A major research topic of the laboratory is to investigate the structure and activity of the regulatory proteins and receptors. This is achieved by in vitro studies with isolated or recombinant proteins and cultured cells, and by investigation of genetic defects in regulatory proteins. Autoantibodies against regulatory proteins occur in many diseases, and these disrupt the complement system. Detection of autoantibodies and determining how they disrupt complement control is a further research interest. The collectins are proteins which recognise invading particles by binding to neutral sugars on the particles: they also promote interaction of the particles with phagocytes. They are particularly important in recognising inhaled particles in the lung. The quaternary structures of these large complex proteins are not yet fully understood, and structural studies, as well as studies of collectin-target interaction are part of the work of the laboratory.
					Group members Visitors Dr Janez Ferluga Carolina Salvador-Morales Krishana Gulla Graduate Students Yuhoi Kang Anders Krarup Maria Carroll Simon Clark Technical Staff Jackie Shaw