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Polly Matzinger
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Section on T cell Tolerance and Memory, Laboratory of Cellular and Molecular Immunology, Bethesda MD, USA
Polly Celine Eveline Matzinger did her Bachelor of Science at the University of California, Irvine, in 1976. In 1979, she graduated Doctor of Philosophy in Biology at the University of California, San Diego. As an NIH overseas fellow she did her post-doctoral work at the Department of Pathology, Cambridge University, United Kingdom, from 1979 to 1983, and was a scientist at the Basel Institute of Immunology, Switzerland until 1989. She returned to the National Institutes of Health in Bethesda, Maryland, where she became head of the Section on T cell Tolerance and Memory, Laboratory of Cellular and Molecular Immunology, the famous “Ghost Lab”. According to Polly Matzinger’s “danger theory” the body does not differentiate between self and non-self but on the basis whether signals represent danger or not.
Being awarded with numerous prizes Polly Matzinger became honorary lifetime member of the Scandinavian Society of Immunology in 1996. In 2002, she was listed as one of “The 50 Most Important Women in Science” by Discover Magazine.
Her scientific achievements can be found in a number of top journals, such as Journal of Experimental Medicine, Nature, Nature Immunology, Nature Medicine, Blood and Science.
Abstract
The immune system has two questions it must answer when faced with a potential threat.
1) shall I respond
2) what kind of response should I make?
For three quarters of a century immunologists trying to discover how the immune system answers the first question have based their theories and experiments on the fundamental belief that the immune system answers this question by discriminating between self and non-self. It was thought (and taught) that, if the system were perfect, it would attack everything that is non-self and be totally tolerant of anything that is self. I abandoned this belief. And suggested instead that the immune system is more concerned with danger than with the distinction between self and non-self. The model starts with the idea that the immune system defines "danger" as anything that causes tissue stress or destruction. Under this model, antigen-presenting cells are activated by alarm signals from stressed or damaged tissues. Without this activation, no primary immune response can occur. I will show some of the recent evidence in its favor and discuss its implications.
I will also present some new ideas about the second question above. Thus far in immunology, there has been no concerted attempt to find a model for how the immune system determines the effector class for any particular response. Currently, it is widely taught that the effector class is tailored to the pathogen driving the immune response: for example, we make IgE to a worm infection, and killer cells against a virus. I no longer believe this. Although pathogens certainly have an influence on the immune responses made against them (usually finding ways to modify those responses to their liking), I believe that there is a more fundamental underlying system of control. I believe that the ultimate controllers of immunity are the tissues that the immune system was designed to protect. When injured, tissues emit alarm signals that initiate immune responses. When not injured, tissues present their own antigens, or release them to passing DCs to present to T cells in order to induce tolerance. And, when an immune response does occur, the tissues send signals that direct the immune system to tailor that response to an effector class that can eliminate the pathogen without causing more damage to the tissue.
We must stop thinking of the immune system as an independent group of cells, patrolling the body to keep it free of foreigners. When we base our thinking on the view that the immune system is an extended family of constantly communicating cells and tissues that accept harmless (and beneficial) entities, while fighting harmful ones, we open new windows, suggest new experiments, and build a new understanding of the complexity and wonder of this powerful system
1. Matzinger P (1994) Tolerance, Danger, and the Extended Family Ann. Reviews of Immunology vol 12:991-1045
2. Matzinger P (2002) The Danger Model: A Renewed Sense of Self. Science 296: 301-305.
3. Seong, Seung and P Matzinger (2004) Hydrophobicity, an ancient Damage-associated Molecular Pattern that initiates Innate Immune Responses. Nature Rev Imm 4:469-78
4. Matzinger P (2007) Friendly and Dangerous signals: Is the Tissue in control? Nature Imm. 8:11-13
5. Ridge, John Paul, E Fuchs, P Matzinger (1996) Neonatal tolerance revisited: Turning on newborn T cells with Dendritic cells Science 271:1723-1726
6. Gallucci, Stefania, M Lolkema and P Matzinger (1999) Natural adjuvants: Endogenous activators of dendritic cells. Nature Medicine 5:1249-1255
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