Complement-dependent defence against bacterial infection. Studies in C2 deficiency

Detta är en avhandling från Institute of Laboratory Medicine, Section of M.I.G., Sölvegatan 23, SE-223 62 Lund, Sweden

Sammanfattning: The complement system is critically involved in defence against bacterial infection. C2 deficiency is, apart from mannan-binding lectin (MBL) deficiency, the most common homozygous complement deficiency among Caucasians. The classical pathway of complement activation is not functional in C2 deficiency and the condition is associated with invasive infections caused by the encapsulated bacteria Streptococcus (S.) pneumoniae, Neisseria (N.) meningitidis and Haemophilus (H.) influenzae type b. In the present investigation we developed an improved method to analyse complement activation mechanisms. We found that vaccination of C2-deficient individuals with capsular polysaccharides of S. pneumoniae, N. meningitidis and H. influenzae type b induced production of antibodies capable of supporting alternative pathway-mediated defence involving bactericidal activity and opsonophagocytosis. Thus, vaccination in C2 deficiency might be meaningful and should be further investigated. Results also indicated that antibodies to some subcapsular antigens of N. meningitidis were strictly dependent on an intact classical pathway for expression of bactericidal activity. This could partly explain the decreased immunity to meningococci in C2 deficiency. Impaired immune responses to the MBL-binding O antigen-specific oligosaccharide of Salmonella serogroup C were found in C2-deficient and MBL-deficient persons. This indicated impaired isotype switching from IgM to IgG and suggested that classical pathway C3-convertase may be involved in maturation of the antibody response to MBL-binding antigens. In further experiments with the oligosaccharide it was found that the MBL pathway could activate C3 and the alternative pathway with circumvention of C4 and C2. This could be an important mechanism of innate immunity.

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