Emory Report

Mar. 22, 1999

Volume 51, No. 24

Ahmed looks for causes of long-term viral immunity Individuals who acquire immunity to diseases such as measles, yellow fever, polio or rubella, either through exposure to disease or through vaccination, are in many cases capable of retaining that immunity for many years or even a lifetime without re-exposure or revaccination, according to Rafi Ahmed, director of the Emory Vaccine Center. Ahmed is working to uncover the specific mechanisms of long-term immune memory that are essential to the development of new and effective vaccines, particularly for diseases like HIV, malaria and tuberculosis. He discussed his recent findings on immune memory during acute and chronic viral infections at the Sixth Conference on Retroviruses and Opportunistic Infections in Chicago. "Understanding immunological memory is the necessary basis of developing any effective vaccine," said Ahmed. "No matter what type of vaccine you are working on or for which disease, you need to understand the mechanisms of immune memory." Acute viral infections induce two types of long-term memory: humoral immunity, in which B cells produce antibodies to prevent infection by viruses; and cellular immunity, in which T cells activated by specific viral antigens kill the virus-infected cells and also produce cytokines, proteins that prevent the growth of viruses and make cells resistant to viral infection. Until recently, scientists believed that plasma cells--the B cells that produce antibodies--live only a short time and that other factors such as re-exposure, chronic infection or cross reactivity with other viruses are necessary to maintain a long-term antibody response. But Ahmed and his colleagues have discovered that although these conditions may play a role, plasma cells (at least in mouse models) actually live for quite a long time, sometimes for the entire life of an organism. If this is true in humans, Ahmed believes it might explain why humoral immunity is capable of such long-term persistence. He and his colleagues have recently received a grant from the National Institutes of Health to extend their studies of immune memory to humans and to explore what specific signals or mechanisms cause some plasma cells to live longer than others. The other aspect of immunity--the response of T cells to viruses--is much different than the B cell response, Ahmed explained. CD8 T cells, which do not prevent infection but instead kill virus after infection, can be divided into three distinct populations: naive CD8 T cells, effector CD8 T cells and memory CD8 T cells. The response to virus by each of these groups of cells is different. Naive CD8 T cells are activated and become effector cells in the presence of antigen. The effector response lasts for only a few weeks, after which the majority of effector cells die and about 5 to 10 percent become memory cells. When memory cells come into contact with the original virus, they are capable of mounting a strong and rapid immune response. The number of effector cells involved in the initial response to disease appears to dictate the number of memory cells remaining, Ahmed said. This means that a strong initial response is critical to generating a large pool of memory T cells and maintaining strong, long-term immunity. Recent research by Ahmed and his colleagues has shown that the stable maintenance of the pool of total memory cells may be dictated by the principle of homeostatis. Models developed by Rustom Antia, an Emory mathematical biologist, suggest that the total number of cells in the immune system is constant and the long-term maintenance of cellular immunity may be regulated by competition for space by immune memory cells. As an individual is exposed to new pathogens, some memory cells may need to make way for new ones. Since the total number of memory cells can be very large, the immune system is normally capable of maintaining immunity to many pathogens at once, especially in the absence of repeated exposures. The impact of new pathogens could govern the loss of existing immune memory cells, however, and might help explain the eventual loss of immune memory to certain viruses. -Holly Korschun Return to March 22, 1999, contents page