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Immunological and molecular analysis of lymphocytes and antigens involved inleprosy (neuritis) lesions

Objective



Mycobacterial diseases like leprosy and tuberculosis are chronic infectious diseases that affect over 45 million people, mainly in developing countries protective immunity against mycobacteria (and other intracellular micro-organisms)is dependent on antigen specific T lymphocytes. T cells recognize mycobacterial antigens as peptides bound to major histocompatibility complex (MHC) molecules on the surface of antigen presenting cells. Upon recognition of peptide and MHC, the T cell is driven into an activation state and subsequently can exert several different effector functions. The functional modalities of T cells however have been incompletely defined and it is unknown which T cell functions are associated with protective immunity and which antigens or MHC determinants preferentially might trigger such functions.
Besides protection however, T cells can also confer immunopathology. This is seen e.g. in leprosy lesions where the cell mediated immune response results in delayed type hypersensitivity reactions with extensive granulomatous inflammation and local tissue destruction. Leprosy predominantly affects skin and nerves. Irreversible damage of the latter tissue is a severe complication of the disease, particularly during reversal reactions, and is responsible for many of the sequelae observed in leprosy. Acute neuritis episodes therefore pose a major obstacle to leprosy control. The study of immunopathology of leprosy is an important objective since it may help in designing measures to control and prevent reactions and nerve damage. So far the mechanism of tissue destruction in general and of neuritis in particular is poorly understood. It is unknown whether particular T cells, T cell functions, T cell (antigen, MHC)specificities, M.leprae antigens are associated with pathology.
The local immune response in leprosy skin and nerve lesions has been analyzed to a limited extent. In order to gain insight into the immunopathology of leprosy lesions, we therefore in the current project propose to study the lymphocytes and M.leprae antigens that may be involved in acute leprosy lesions, using a variety of molecular and cellular techniques. We will also start to investigate the possible auto antigens that may be involved.

Topic(s)

Data not available

Call for proposal

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Coordinator

Rijksuniversiteit Leiden
Address
10,Rijnsburgerweg
2300 RC Leiden
Netherlands
 

Participants (2)

ARMAUER HANSEN RESEARCH INSTITUTE
Ethiopia
Address
1005
2003 Addis Abeba
 
Medical Research Council (MRC)
United Kingdom
Address
20 Park Crescent
W1N 4AL London