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286:). The alarm signals released by these cells let the immune system know that there is a problem requiring an immune response. She argued that T cells and the immune response they orchestrate occurs not because of a neonatal definition of "self", as in the previous model, nor because of ancient definitions of pathogens, as in Janeway's argument, but because of a dynamic and constantly updated response to danger as defined by cellular damage.
31:
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and
Matzinger have proposed exposed hydrophobic regions on biological compounds as among the damage-associated molecular patterns (DAMPs) of the danger model. Facing stressors, cells misfold and denature their proteins, exposing hydrophobic regions that aggregate into clumps to avoid exposure to the
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The danger model is broad, covering topics as diverse as transplantation, maternal/fetal immunity, autoimmunity, cancer treatments, and vaccines. Matzinger argues that prior models failed to explain why immune system responses vary based on the specific threat's location and severity. Prior models
375:", are frequently repurposed for explanations of the self/non-self model of the immune system. The immunologist Russell E. Vance has argued that immunological paradigms like the danger model are inevitably inaccurate representations of distinct mechanisms generated under evolutionary pressure.
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Criticisms of the danger model focus on two key points: First, Matzinger argued that tumors persist to cause cancer because their cells undergo programmed cell death, failing to release danger signals for an immune response. However, recent research has shown the immune system detecting and
151:
Polly
Matzinger was born on July 21, 1947, in France, to a French mother (Simone) and a Dutch father (Hans). In 1954, she immigrated to the US with her sister, Marjolaine, and parents. Her prior jobs included being a bass jazz musician, carpenter, dog trainer, waitress, and
302:
Some immunologists still maintain
Janeway's ideas, believing that the immune response is mainly fueled by innate evolutionarily conserved "pattern recognition receptors" that recognize similarities between microorganisms, minimizing the effects of unprogrammed cell death.
277:
In her 1994 article "Tolerance, Danger, and the
Extended Family", Matzinger extended the danger model, arguing that antigen-presenting cells respond to "danger signals" released from cells undergoing unprogrammed cell death when injured or stressed, as opposed to
264:
made a 1989 proposal that the innate immune system was the real gatekeeper of immune system responses. He also theorized that the innate immune system used ancient pattern-recognition receptors to make these decisions, recognizing a
355:
cells into her danger model, arguing that their regulation activity is not absolute, based on transplant organs being rejected at higher rates if infected, showing that danger signals continue to dictate the immune response.
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respond to both external and endogenous ligand signals with her danger model suggesting a multitude of signalling pathways determining the extent and nature of each immune system response.
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324:, Matzinger highlighted the danger model's primary implication that bodily tissues drive immune responses. As research continues to show the bacteria of each organ's
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1913:
1650:"In A Fully H-2 Incompatible Chimera, T Cells of Donor Origin Can Respond to Minor Histocompatibility Antigens in Association With Either Donor or Host H-2 Type"
457:"In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type"
328:
guiding its function and outputs, Matzinger theorizes that microbes may be shown as driving immune system responses. Matzinger argues that DAMPs may explain why
1928:
1141:
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Ridge J.P.; Di Rosa F.; Matzinger P. (1998). "A conditioned dendritic cell can be a temporal bridge between a CD4+ T helper cell and a T- killer cell".
1918:
939:. Matzinger P and André Trauneker (1986) (video, 13 min). Award-winning animated film for lay people describing the events involved in clearing an
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192:. The lab has been referred to as the "Ghost Lab" for Matzinger's choice to conduct the first nine months of her research alone with a focus on
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and the multitude of organisms that live on and within them. The film features the Danger model as the model of immunity that best allows for
196:. In 2013, while reorganizing the Laboratory of Cellular and Molecular Immunology, NIAID transferred Matzinger's section to the Laboratory of
1933:
768:
Seong S., Matzinger P. (2004). "Hydrophobicity, an ancient Damage-associated
Molecular Pattern that initiates Innate Immune Responses".
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224:
161:
74:
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Since 2009, the biotechnology company EpiVax has funded the Polly
Matzinger Fearless Scientist Scholarship for women scientists at the
1888:
160:, in 1976. She was talked into going to graduate school by Professor Robert Schwab of UC Davis and finished her PhD in biology at the
1719:
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Perez-Diez Ainhoa; Joncker
Nathalie T.; Choi Kyungho; Chan William F. N.; Anderson Colin C.; Lantz Olivier; Matzinger Polly (2007).
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to write in a third-person active voice. Upon identifying the misconduct, she was banned from publishing in the journal.
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956:. Matzinger P. (1991) (Video, 2 min). Animated film for lay people describing the events that result in rejection of a
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420:. In 1996, she was inducted as an honorary lifetime member of the Scandinavian Society of Immunology. In 2002,
249:
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156:. Although it took her eleven years to finish her undergraduate degree, she finished her BS in biology at the
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Gallucci S.; Lolkema M.; Matzinger P. (1999). "Natural adjuvants: Endogenous activators of dendritic cells".
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magazine recognized
Matzinger as one of the fifty most important women in science. In 2003, she received an
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416:, Polly Matzinger won the Award for Special Excellence in Educational Films for the German translation of
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as the result of surgery-induced damage, but this explanation fails to account for greater tolerance of
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1309:"Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses"
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In 2015, Matzinger recorded an eight-part series on the danger model of the immune system, covering
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1142:"A Conversation With Polly Matzinger; Blazing an Unconventional Trail to a New Theory of Immunity"
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Terms coined by
Matzinger, such as "professional antigen-presenting-cell", "danger signal", and "
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in 1949 faced challenges in the late 1980s as immunologists recognized that T cells depend on
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975:. Peter Friedman and Jean-François Brunet (1995) (Film, 73 minutes). Award-winning film on
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showcasing materials and sending co-stimulatory signals. Driven by the writings of
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1584:"Cutting Edge Commentary: A Copernican Revolution? Doubts About the Danger Theory"
1421:"Disruption of the Epidermal Barrier Induces Regulatory T Cells via IL-33 in Mice"
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Bruhs, Anika; Proksch, Ehrhardt; Schwarz, Thomas; Schwarz, Agatha (2018-03-01).
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585:"Neonatal tolerance revisited: turning on newborn T cells with dendritic cells"
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1015:(2001) (Film, 60 minutes). A program describing the interrelationship between
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have been shown suppressing immune responses, exemplified by the autoimmune
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Matzinger is chief of the T-Cell
Tolerance and Memory Section at the U.S.
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for a meeting of television producers. NIH special events department and
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445:'s Institute for Immunology & Informatics that overcome challenges.
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1112:"Polly Matzinger: De conejita playboy a paradigma de la inmunología"
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889:"CD4 cells can be more efficient at tumor rejection than CD8 cells"
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also fail to explain how the immune system rejects tumors, induces
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cell death that features the work of six scientists. P Matzinger,
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645:
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Matzinger P (1994). "Tolerance, Danger, and the Extended Family".
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National Institute of Allergy and Infectious Diseases (NIAID)
1470:"Friendly and dangerous signals: is the tissue in control?"
1364:"Friendly and Dangerous Signals: Is the Tissue in Control?"
807:"Friendly and dangerous signals: is the tissue in control?"
360:
destroying some tumors. Second, the danger model explains
1708:
Bold Science: Seven Scientists Who Are Changing Our World
983:, M Raff, P Golstein, KM Debatin, R Horowitz among others
848:"Tissue-based class control: the other side of tolerance"
368:, the movement of tissue between parts of the same body.
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Immunology Course based on the Danger Model: Session 1
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Lassila, O., Vainio, O. and Matzinger, P. (1988). Can
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In 1978, Matzinger published her fourth paper in the
307:
Pattern recognition and a tissue-driven immune system
117:
National Institute of Allergy and Infectious Diseases
1845:
Death by Design/The Life and Times of Life and Times
1307:
Seong, Seung-Yong; Matzinger, Polly (June 1, 2004).
1211:
National Institute of Allergy and Infectious Disease
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Death by Design/The Life and Times of Life and Times
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cells is dysfunctional. Matzinger has incorporated T
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37:
21:
515:"B cells turn off virgin but not memory T cells"
347:occurring when the master regulator of these T
8:
1648:Polly Matzinger; Galadriel Mirkwood (1978).
1260:"Tolerance, Danger, and the Extended Family"
1633:: CS1 maint: numeric names: authors list (
943:. Translated into German, French, Spanish.
708:"The Danger Model: A Renewed Sense of Self"
583:Ridge J.P.; Fuchs E.; Matzinger P. (1996).
1904:University of California, San Diego alumni
1763:"Polly Matzinger Fearless Scientist Award"
29:
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1737:"The 50 Most Important Women in Science"
1924:University of California, Irvine alumni
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962:National Association of Science Writers
1626:
1523:Pradeu, Thomas; Cooper, Edwin (2012).
131:(born July 21, 1947) is a French-born
1914:French emigrants to the United States
176:for six years, before heading to the
7:
1929:National Institutes of Health people
1468:Matzinger, Polly (January 1, 2007).
1425:Journal of Investigative Dermatology
1362:Matzinger, Polly (January 1, 2007).
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1154:from the original on 18 January 2015
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240:The Self/Non-self Model proposed by
164:in 1979. She then did four years of
1525:"The danger theory: 20 years later"
1278:10.1146/annurev.iy.12.040194.005015
1118:(in European Spanish). 2018-04-29.
568:10.1146/annurev.iy.12.040194.005015
299:, or generates allergic responses.
269:by its unchanging characteristics.
162:University of California, San Diego
75:University of California, San Diego
1735:Svitil, Kathy (13 November 2002).
1140:DREIFUS, CLAUDIA (June 16, 1998).
1047:Oakes, Elizabeth H. (2014-05-14).
513:Fuchs E., Matzinger P. B. (1992).
455:Matzinger P., Mirkwood G. (1978).
336:Challenges to Matzinger's theories
14:
1074:Cooper, Glenda (April 16, 1997).
16:French-born American immunologist
1919:American people of Dutch descent
1827:British Journal of Ophthalmology
1743:from the original on 11 May 2019
1691:
1655:Journal of Experimental Medicine
1582:Russell E. Vance2 (2000-08-15).
1179:Encyclopedia of World Scientists
954:A quick look at tissue rejection
461:Journal of Experimental Medicine
386:Journal of Experimental Medicine
158:University of California, Irvine
66:University of California, Irvine
1855:Publications by Polly Matzinger
1794:from the original on 2013-10-17
1616:from the original on 2008-10-06
1258:Matzinger, Polly (April 1994).
1232:Matzinger, Polly (2015-09-22),
1122:from the original on 2018-07-27
1088:from the original on 2018-07-27
1594:(4). Jimmunol.org: 1725–1728.
1001:featuring and delineating the
846:Matzinger P, Kamala T (2011).
174:Basel Institute for Immunology
129:Polly Celine Eveline Matzinger
1:
1240:National Institutes of Health
993:(1997) (Film, 60 minutes). A
609:10.1126/science.271.5256.1723
178:National Institutes of Health
1176:Oakes, Elizabeth H. (2007).
905:10.1182/blood-2006-10-051318
1934:21st-century American women
1601:10.4049/jimmunol.165.4.1725
1265:Annual Review of Immunology
556:Annual Review of Immunology
172:and was a scientist at the
1950:
937:Immunity: the inside story
443:University of Rhode Island
418:Immunity: The Inside Story
315:water-filled environment.
1889:American women biologists
1816:Matzinger's farm homepage
1712:W. H. Freeman and Company
1588:The Journal of Immunology
1438:10.1016/j.jid.2017.09.032
1313:Nature Reviews Immunology
852:Nature Reviews Immunology
770:Nature Reviews Immunology
379:Dog co-author controversy
122:
95:
28:
1542:10.3389/fimmu.2012.00287
1207:"Polly Matzinger, Ph.D."
1050:A to Z of STS Scientists
501:turn on virgin T cells?
335:
250:antigen-presenting cells
1790:. Strange Attractions.
1529:Frontiers in Immunology
1182:. Infobase Publishing.
1053:. Infobase Publishing.
1021:symbiotic relationships
745:10.1126/science.1071059
539:10.1126/science.1439825
180:in Bethesda, Maryland.
170:University of Cambridge
1879:American immunologists
1818:, (Ambling Brook Farm)
960:. Commissioned by the
318:In a 2013 article in
1668:10.1084/jem.148.1.84
1025:The Learning Channel
805:Matzinger P (2007).
706:Matzinger P (2002).
473:10.1084/jem.148.1.84
362:transplant rejection
205:transplant rejection
1884:Women immunologists
1706:Anton, Ted (2000).
987:Turned on by Danger
941:influenza infection
727:2002Sci...296..301M
601:1996Sci...271.1723R
595:(5256): 1723–1726.
531:1992Sci...258.1156F
525:(5085): 1156–1159.
366:autotransplantation
330:toll-like receptors
297:autoimmune diseases
1147:The New York Times
949:Basel, Switzerland
432:Hasselt University
428:honorary doctorate
414:Köln Film Festival
341:Regulatory T cells
184:Ghost Lab at NIAID
139:theory of how the
1909:Humour in science
1833:Matzinger profile
1822:Matzinger profile
1788:"Death By Design"
1486:10.1038/ni0107-11
1474:Nature Immunology
1382:10.1038/ni0107-11
1369:Nature Immunology
1116:Procrastina Fácil
1023:within the body.
999:public television
997:program made for
981:R Levy-Montalcini
945:Hoffmann-La Roche
899:(12): 5346–5354.
823:10.1038/ni0107-11
811:Nature Immunology
721:(5566): 301–305.
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321:Nature Immunology
242:Macfarlane Burnet
135:who proposed the
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213:autoimmunity
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194:chaos theory
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168:work at the
166:postdoctoral
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137:danger model
133:immunologist
128:
127:
113:Institutions
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90:Danger model
1899:1947 births
1013:David Green
995:BBC Horizon
254:Thomas Kuhn
147:Early years
1873:Categories
1798:2013-10-17
1773:2023-01-10
1620:2013-08-01
1245:2023-01-10
1218:2023-01-10
1126:2018-07-27
1092:2018-07-27
1031:References
958:skin graft
326:microbiome
284:cell death
107:Immunology
44:1947-07-21
1551:1664-3224
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1390:1529-2916
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395:Galadriel
280:apoptosis
221:parasites
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