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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.
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 hosts 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
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.