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The Role of Complement in Susceptibility to Infection and Chronic Disease

Objective

1. Optimization of purification and storage of complement proteins and their distribution to other laboratories.
2. Comparison of monoclonal and polyclonal antibodies and assay reagents testing of their utility in assays of complement component concentrations and complement fixation.
3. Production of selected antibodies and assay reagents on a scale sufficient for distribution.
4. Use of antibodies and assay reagents to screen for complement component deficiencies in patients and controls.
5. Detailed study of complement component interaction with microorganisms of current public health interest.

Human resistance to microbial infection is mediated by humoral and cellular effector systems. A major part of the humoral immune system is complement. Complement consists of a group of 30-35 soluble and cell-surface proteins which recognize and are of utmost importance in the elimination of viruses, bacteria, fungi and multicellular parasites. Complement is a major mediator of clearance of immune complexes, viruses and bacteria from the blood.
Diminished complement activity, arising from genetic defects or from consumption of complement, causes humans to become susceptible to repetitive fulminant or severe infections, and/or to suffer from immune complex deposition diseases, such as systemic lupus erythematosus, rheumatoid arthritis and renal disease. Excessive complement activation, occurring after tissue injury or massive infection, leads to acute or chronic inflammation, and itself directly causes damage to host tissue. The proteins of the complement system are well-characterized at the molecular/biochemical level, and many functions of the proteins are understood from in vitro experiments. In vivo, however, the complexity of function of the complement system is incompletely understood.
The aim of this project is the development/facilitation and coordination of distribution of specialized complement reagents and assay systems, and training in their use for elucidating the role of complement in bacterial, fungal and viral infections

Funding Scheme

CON - Coordination of research actions

Coordinator

Rijksuniversiteit Leiden
Address
10,Rijnsburgerweg
2333 AA Leiden
Netherlands