University of Leicester eBulletin

Maintaining the Body's Defences - New Approaches Investigated at University of Leicester

May 2003
No 141

New 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.

Professor 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.

Professor 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.

It 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.

“Modulation of the innate immune response has therefore a high therapeutic potential in the treatment of human morbidity and mortality,” said Professor Schwaeble.

A scientific summary of the lecture follows:

The 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 immunological 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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