SARS Epidemiology Modeling

Both in vitro and in vivo animal and human studies demonstrate age-related declines in both humeral and cellular components of the immune system (9). In old (23 months) mice, the normal functioning of follicular dendritic cells appears to be strongly impaired when compared with young mice (10); according to researchers, “Antigen transport was defective and only a small fraction of antigen transport sites developed.” (10). Furthermore, follicular dendritic cells were ultrastructurally atrophic, retained little antigen, and produced no iccosomes. By interfering with normal follicular dendritic cell function, age likely has the same effect on transmissible spongiform encephalopathies as has been observed due to dedifferentiation of follicular dendritic cells (8). Senescence of the immune system function could interfere with transmissible spongiform encephalopathy pathogenesis in other ways as well, such as impairing migrating intestinal dendritic cells or complement pathways involved in complexing PrPRes to follicular dendritic cells. This hypothesis could be readily tested by intracerebral versus peripheral PrPRes challenge of young versus old animals. Because the intracerebral challenge bypasses the immune system portal, old, peripherally challenged animals should show a disproportionate reduction in disease risk if immune system senescence is important in regulating pathogenesis.