Polly Matzinger PhD, Honorary D Phil, is a world renowned immunologist, who began a new paradigm in Immunology with the publication of her “Danger Model” of immunity. and has won several awards, as well as been featured in several films because of her work, including a one-hour BBC documentary on the Danger model titled “Turned on by Danger”. In her pre-scientific life she worked as a bartender, carpenter, jazz musician, playboy bunny, and dog trainer. She is currently the chief of the Ghost lab, and the section on T cell Tolerance and Memory at the National Institutes of Health. She worried for years that the dominant model of immunity does not explain a wealth of accumulated data and proposed 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 has featured in three other films about immunity, and countless articles in both the scientific and the lay press. In her spare time, Polly trains border collies for competitive shepherding trials, composes songs that are not really worth listening to, and is working on the next major question in the immune system, namely "once it decides to respond, how does the immune system 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”. This has major implications for autoimmunity, cancer immunotherapy, and vaccine design. Finally, she is also a sheep breeder, and is part of a small group bringing Gotland sheep into the USA, using frozen embryos from New Zealand and semen from Sweden. She is currently president of the Gotland Sheep Breeders Association of North America, and vice president of the Frederick Sheep Breeders Association.
Most textbooks teach that the immune system functions by discriminating self (defined early in life) from nonself (what comes later). Although this elegantly simple idea once seemed sensible, it has failed over the years to explain a great number of findings. For example, how do organisms go through puberty, metamorphosis, pregnancy, and aging without attacking newly changed tissues? Why do mammalian mothers not reject their fetuses or attack their newly lactating breasts, which produce milk proteins that were not part of earlier “self ”? Why do vaccines need adjuvants? Why do tumors grow, even when many express new or mutated proteins? Why do most of us harbor autoreactive lymphocytes without any sign of autoimmune disease, while a few individuals succumb?
The Danger model suggests that immune responses are initiated by alarm signals from injured tissues, rather than by the recognition of nonself. Although this basic assumption is very simple, it allows us to explain most of what the immune system does right………and also most of what it seems to get wrong. Although many immunology classes now include parts of the Danger model, it is regrettably still not being applied to a wide range of immunological phenomena. In this talk I will cover some of those, comparing the predictions of the self-non-self models of the ‘50s, the “extended non self” model of Janeway, and the Danger model.