Immunological and Molecular Analysis in Elderly and Young Adults in Response to Pneumococcal Polysaccharides 4 and 14
Streptococcus pneumoniae is a major human pathogen in both developing and developed countries. Studies indicate that the age related incidence of pneumococcal bacteremia mainly occurs at the extreme ends of age. Mortality from bacteremic pneumonia increases with age and is 3-5x higher in elderly than young adults. S. pneumoniae is the most common organism isolated from elderly patients with pneumonia. The present pneumococcal capsular polysaccharide vaccine is based on the observation that antibodies against the capsule protect against disease by enhancing phagocytosis. Since polysaccharides are T-independent type 2 (TI-2) antigens this vaccine has poor efficacy in groups at highest risk for pneumococcal infection. Vaccine efficacy studies in elderly suggest that despite normal antibody levels, the elderly exhibit decreased vaccine efficacy. Furthermore, data from aged mice in response to TI-2 antigens demonstrate a decline in antibody affinity, fine specificity, and a general loss of protective immunity is associated with molecular changes in variable gene family usage. We hypothesized that the reduced efficacy of the pneumococcal polysaccharide vaccine in the elderly results from altered variable gene family usage. We investigated the overall immune response in young and elderly adults in response to pneumococcal polysaccharides. Specifically we focused on both the quantitative and qualitative changes in the immune response on molecular and functional levels. Correlations were determined between variable gene usage, functional activity, antibody avidity, and antibody concentration as a function of age.
School:University of Toledo Health Science Campus
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:streptococcus pneunomiae polysaccharide immunoglobulin gene usage heavy chain elderly adults serotype 4 and 14
Date of Publication:01/01/2005