Immunologic aspects of cystic fibrosis

Bacterial infections determine life expectancy in the hereditary disease cystic fibrosis (CF). The dominant pathogens are Staphylococcus aureus and Pseudomonas aeruginosa, which persist in the patient's respiratory tract. Current explanations of the chronicity of the infections in the apparently immunocompetent host are based on defective opsonophagocytosis. This may be caused by (1) bacterial exopolysaccharide production, leading to cryptic infection types; (2) cleavage of immunoglobulin, complement, and surface receptors on immunocompetent cells by host proteases; and (3) a change from opsonic to nonopsonic antibody isotypes. Continuous antigenic stimulation of the immune system leads to local immune complex formation and a high chronic hypersensitivity reaction as well as to temporary immune unresponsiveness. Progressive tissue damage caused by lysosomal enzymes and oxygen radicals from polymorphonuclear leukocytes is thought to be ultimately responsible for respiratory failure and death in CF. Besides antibiotic treatment, anti-inflammatory therapy is therefore currently considered beneficial.