Immunology of cystic fibrosis

The combination of all the immunological abnormalities described in CF appear to have a final common pathway through effects on neutrophils. Potent neutrophil chemotactic factors are produced as a result of antibody-antigen interactions leading to complement activation and the generation of C5a and the many cytokines released as a result of cellular immune responses leading to neutrophil influx and activation. In addition, the product of bacterial metabolism fMLP also produces neutrophil chemotaxis. The activated neutrophils release a range of proteases and oxygen radicals which directly damage tissues. It can, therefore, be hypothesised that the excessive immune response is directly contributing to the tissue damage. Indeed, it is even possible that this is the principal cause of the lung function defect without invoking any direct influence of the infecting organisms. This, of course, has major implications for approaches to therapy. Currently the main focus is on suppression of the organisms. However, modulation of the immune response is an attractive alternative approach.