Program Description The T-Cell Tolerance and Memory Section is engaged in elucidating the answers to fundamental questions in immunology: What turns an immune response on and off? How does the immune system remember its past encounters? What regulates the effector class of an immune response? How do tissues control local and systemic immunity? The next major question of interest is, once the immune system decides to respond, how does it know what kind of response to make? A first answer to this question seems to be “local tissues send instructions to immune cells, guiding them to make the right kind of response.” The answer to this question has major implications for autoimmunity, cancer immunotherapy, and vaccine design. Anyone interested in pursuing these questions, and who would like to have conversations about these topics, please contact Dr. Matzinger. Biography Polly Matzinger has worked as a bartender, carpenter, jazz musician, playboy bunny, and dog trainer. She is currently chief of the ghost lab and the section on T-Cell Tolerance and Memory. She worried for years that the dominant model of immunity does not explain a wealth of accumulated data and suggested an alternative, the Danger model, which suggests that the immune system is far less concerned with things that are foreign than with those that do damage. This model, whose two major tenets were conceived in a bath and on a field while herding sheep, has very few assumptions and yet explains most of what the immune system seems to do right, as well as most of what it appears to do wrong, covering such areas as transplantation, autoimmunity, and the immunobiology of tumors. The model has been the subject of a BBC "horizon" film and was featured in three other films about immunity, as well as countless articles in both the scientific and the lay press. In 2013, her section was assigned to the Laboratory of Immunogenetics.

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