Body's Defences - New Approaches Investigated at University of Leicester
advances in medical research that have the potential of enhancing our quality of
life were discussed at a recent public lecture at the University of Leicester.
Wilhelm Schwaeble delivered his inaugural lecture, Learning about New Tricks
from an Old Dog: How Understanding Innate Immunity could Enhance Quality of
Life, on Tuesday, May 27.
Schwaeble, who is Professor of Immunology at Leicester, said that scientists at
the University of Leicester are conducting pioneering research in a novel field
of immunology that is essential for the maintenance of the body's defences and
provides protection even when other immune mechanisms were dysfunctional.
is therefore particularly relevant for the very young, the very old and very ill
patients, and patients undergoing cytostatic therapy and transplantation.
However, medical scientists have also identified problems that may arise from
‘overshooting’ activation of this innate defence system.
of the innate immune response has therefore a high therapeutic potential in the
treatment of human morbidity and mortality,” said Professor Schwaeble.
scientific summary of the lecture follows:
immune system controls the integrity of our body: It protects us from microbial
infection and fulfils essential policing and scavenger functions by sensing
abnormal tissue growth and by removing apoptotic and necrotic cells and debris.
One of the most striking developments in current
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research is the reappraisal of innate immunity. The innate immune system
provides a critical first line defence to maintain health. With the last few
years, our knowledge of the molecular mechanisms that compose our innate immune
system has progressed tremendously. We now understand how our body specifically
responds to molecular patterns and structures of pathogens by triggering
cellular and humoral responses through pattern recognition molecules, even in
total absence of adaptive immunity. The lectin pathway of complement activation
is a humoral defence system driven by multimeric pattern recognition molecules
present in plasma and other body fluids. Activation of the lectin pathway is
initiated when lectin pathway recognition molecules specifically bind to
microbial carbohydrates. Binding of the lectin pathway carbohydrate
recognition molecules is translated into antimicrobial and cytotoxic activities
through an enzyme that was first cloned and characterised in Leicester. This
effector component of the lectin pathway is a serine protease of 76kDa, termed
MASP-2 (for Mannan binding lectin Associated Serine Protease-2). The Leicester
team has established the genomic organisation of human and murine MASP2 and its
clustered genes and developed assays to screen for polymorphisms and
deficiencies of MASP-2 and the lectin pathway as inherited predispositions for
human disease. The discovery of the lectin pathway has raised a broad interest
within the Medical Community as this defense route maintains immunity under
situations where the adaptive immune response is dysfunctional, i.e. in the very
young, the very old and the very ill patients, in patients undergoing cytostatic
therapy and transplantation. On the other hand, it has become clear that
overshooting responses of the lectin pathway may significantly contribute to the
pathophysiology of cerebral, myocardial and gut infarction, septic shock
syndrome and perhaps to autoimmune disease. Modulation of the innate immune
response has therefore a high therapeutic potential in the treatment of human
morbitity and mortality.
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