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{{short description|French-born American immunologist}}
{{BLP sources|date=January 2013}}
{{Infobox scientist
]
| name = Polly Matzinger
| image = Polly Matzinger.jpg
| birth_date = {{Birth date and age|1947|7|21|mf=yes}}
| birth_place = ]
| fields = ]
| workplaces = ]
| alma_mater = ] (]) <br> ] (])
| known_for = ]
}}


'''Polly Celine Eveline Matzinger''' (born July 21, 1947 in ], ]) is an ] who proposed the ] theory of how the ] works.<ref name=":0">{{Cite book|url=https://books.google.com/books?id=1YDrMFug17cC&pg=PA192&lpg=PA192&dq=Polly+Celine+Eveline+Matzinger&source=bl&ots=-tLzSpvbJ1&sig=DEhY6KqU8UQJPpW8AgUYpfAj4oA&hl=en&sa=X&ved=2ahUKEwiLqIH3j7_cAhWrwFQKHQFPADsQ6AEwDHoECAcQAQ#v=onepage&q=Polly%20Celine%20Eveline%20Matzinger&f=false|title=A to Z of STS Scientists|last=Oakes|first=Elizabeth H.|date=2014-05-14|publisher=Infobase Publishing|isbn=9781438109251|language=en}}</ref> '''Polly Celine Eveline Matzinger''' (born July 21, 1947) is a French-born ] who proposed the ] theory of how the ] works.<ref name=":0">{{Cite book|url=https://books.google.com/books?id=1YDrMFug17cC&q=Polly+Celine+Eveline+Matzinger&pg=PA192|title=A to Z of STS Scientists|last=Oakes|first=Elizabeth H.|date=2014-05-14|publisher=Infobase Publishing|isbn=9781438109251|language=en}}</ref>


==Early years== ==Early years==
Polly Matzinger was born in July 21, 1947 in France, of a French mother (Simone) and a Dutch father (Hans).<ref name=":0" /> She immigrated to the US, along with her parents and sister (Marjolaine) in 1954. Before finishing university, she worked at many different kinds of jobs. She was a jazz musician (playing the string bass), a carpenter, a dog trainer, a waitress, and a ].<ref>{{Cite news|url=https://www.independent.co.uk/life-style/clever-bunny-1267594.html|title=Clever bunny|work=The Independent|access-date=2018-07-27|language=en-GB}}</ref><ref name=":1">{{Cite news|url=https://procrastinafacil.com/polly-matzinger-playboy-paradigma-inmunologia/|title=Polly Matzinger: De conejita playboy a paradigma de la inmunología|date=2018-04-29|work=Procrastina Fácil|access-date=2018-07-27|language=es-ES}}</ref> Although it took her eleven years to finish her undergraduate degree, she finished her BS in biology at the ] in 1976.<ref name=":1" /> She was talked into going to grad school by Professor Robert Schwab of UC Davis and finished her PhD in Biology at the ] in 1979.<ref>{{cite web|url= https://www.nytimes.com/1998/06/16/science/conversation-with-polly-matzinger-blazing-unconventional-trail-new-theory.html| title= A Conversation With Polly Matzinger; Blazing an Unconventional Trail to a New Theory of Immunity| last= DREIFUS | first= CLAUDIA |date= June 16, 1998| website= Nytimes.com|accessdate= 19 Jan 2015}}</ref><ref name=":2">{{Cite book|url=https://books.google.com/books?id=uPRB-OED1bcC&pg=PA488&lpg=PA488&dq=Polly+Celine+Eveline+Matzinger&source=bl&ots=8YdwW1mvKB&sig=32eFq50oIbdhtn7eUKESHxV6G_M&hl=en&sa=X&ved=2ahUKEwiLqIH3j7_cAhWrwFQKHQFPADsQ6AEwDXoECAgQAQ#v=onepage&q=Polly%20Celine%20Eveline%20Matzinger&f=false|title=Encyclopedia of World Scientists|last=Oakes|first=Elizabeth H.|date=2007|publisher=Infobase Publishing|isbn=9781438118826|language=en}}</ref> Polly Matzinger was born on July 21, 1947, in France to a French mother (Simone) and a Dutch father (Hans).<ref name=":0" /> In 1954, she immigrated to the U.S. with her sister, Marjolaine, and parents. Her prior jobs included being a bass jazz musician, carpenter, dog trainer, waitress, and ].<ref>{{Cite news |last=Cooper |first=Glenda |date=April 16, 1997 |title=Clever Bunny |language=en-GB |work=] |url=https://www.independent.co.uk/life-style/clever-bunny-1267594.html |url-status=live |access-date=2018-07-27 |archive-url=https://web.archive.org/web/20180727174239/https://www.independent.co.uk/life-style/clever-bunny-1267594.html |archive-date=2018-07-27}}</ref><ref name=":1">{{Cite news|url=https://procrastinafacil.com/polly-matzinger-playboy-paradigma-inmunologia/|title=Polly Matzinger: De conejita playboy a paradigma de la inmunología|date=2018-04-29|work=Procrastina Fácil|access-date=2018-07-27|language=es-ES|archive-url=https://web.archive.org/web/20180727150435/https://procrastinafacil.com/polly-matzinger-playboy-paradigma-inmunologia/|archive-date=2018-07-27|url-status=live}}</ref> She finished her bachelor's of science in biology at the ] in 1976,<ref name=":1" /> and doctorate in biology at the ] in 1979.<ref>{{cite web|url= https://www.nytimes.com/1998/06/16/science/conversation-with-polly-matzinger-blazing-unconventional-trail-new-theory.html|title= A Conversation With Polly Matzinger; Blazing an Unconventional Trail to a New Theory of Immunity|last= DREIFUS|first= CLAUDIA|date= June 16, 1998|website= ]|access-date= 19 Jan 2015|archive-url= https://web.archive.org/web/20150118115533/http://www.nytimes.com/1998/06/16/science/conversation-with-polly-matzinger-blazing-unconventional-trail-new-theory.html|archive-date= 18 January 2015|url-status= live}}</ref><ref name=":2">{{Cite book|url=https://books.google.com/books?id=uPRB-OED1bcC&q=Polly+Celine+Eveline+Matzinger&pg=PA488|title=Encyclopedia of World Scientists|last=Oakes|first=Elizabeth H.|date=2007|publisher=Infobase Publishing|isbn=9781438118826|language=en}}</ref> She then did four years of ] work at the ]<ref name=":1" /> and was a scientist at the ] for six years before working at the ] in Bethesda, Maryland.<ref name=":2" />
She then did four years of ] work at the ]<ref name=":1" /> and was a scientist at the ] for six years, before heading to the ] in Bethesda, Maryland.<ref name=":2" />


==Ghost Lab at NIAID== ==Ghost Lab at NIAID==
Matzinger is chief of the T-Cell Tolerance and Memory Section at the U.S. ].<ref name=":3">{{Cite web |date=July 19, 2022 |title=Polly Matzinger, Ph.D. |url=https://www.niaid.nih.gov/research/polly-matzinger-phd |access-date=2023-01-10 |website=] |language=en}}</ref> 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 ].{{cn|date=December 2024}} In 2013, while reorganizing the Laboratory of Cellular and Molecular Immunology, NIAID transferred Matzinger's section to the Laboratory of ].<ref name=:3 />
Polly Matzinger was a section head at the U.S. ] (NIAID) until April 2013. Matzinger and her coworkers referred to the lab as the "Ghost Lab" when listing their affiliation in papers. The nickname was given to the lab by her colleagues when Matzinger first arrived at the NIH because she spent the first nine months studying a new field (]) that she thought might apply to the immune system, and the lab sat empty. The formal name of her laboratory was the ] Tolerance and Memory Section of the Laboratory of Cellular and Molecular Immunology.<ref>{{Cite web|url=https://www.niaid.nih.gov/research/lab-immunogenetics|title=Laboratory of Immunogenetics {{!}} NIH: National Institute of Allergy and Infectious Diseases|website=www.niaid.nih.gov|language=en|access-date=2018-07-27}}</ref> On average, the Ghost Lab hosted three postdoctoral researchers at any one time.<ref>{{cite web|url=http://www3.niaid.nih.gov/labs/aboutlabs/lcmi/tCellToleranceMemorySection/ |title=Polly Matzinger, Ph.D., T-Cell Tolerance and Memory Section, Laboratory of Immunogenetics, NIAID, NIH |publisher=.niaid.nih.gov |date=2013-03-27 |accessdate=2013-08-01}}</ref>


In 2015, Matzinger recorded an eight-part series on the danger model of the immune system, covering ], ], ], ], ], and ].<ref>{{Citation |last=Matzinger |first=Polly |title=Immunology Course based on the Danger Model: Session 1 |date=2015-09-22 |url=https://videocast.nih.gov/watch=17095 |publisher=] |access-date=2023-01-10}}</ref>
On April 1, 2013, NIAID administration closed the Ghost Lab.<!-- why? lack of funding? --> The T-Cell Tolerance and Memory Section was incorporated into the Laboratory of ], but without any funding for research, and Matzinger's research was effectively shut down. Since that time she has given a series of eight lectures explaining the function of the immune system from the point of view of the danger model. These lectures were taped and can be found on the NIH videocast website<ref>{{Cite web|url=https://videocast.nih.gov/|title=NIH VideoCasting and Podcasting|last=NIH|website=videocast.nih.gov|language=en-us|access-date=2018-02-06}}</ref>. The lectures cover immunological theory, ], pregnancy, tumors, ], ], tissue control of immunological class, allergy, parasites and the nature of ].


== Research == == Research ==
===The danger model=== ===The danger model===
The Self/Non-self Model proposed by ] and ] in 1949 faced challenges in the late 1980s as immunologists recognized that T cells depend on ] showcasing materials and sending co-stimulatory signals. Driven by the writings of ] on ] in science, ] 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 ] by its unchanging characteristics.{{cn|date=December 2024}}
The self/non-self model, the predominant model in immunology since the ], began to encounter problems in the late 1980s when immunologists began to recognize that T cells depend on other cells to pick up and then present the things to which they will respond &mdash; and that the ] depends on whether the other cell (known as ]) is sending activation signals to the T cells.

In 1989, drawing on the ideas of ], ] proposed that the old immunological ] had reached the limits of its usefulness—or, as he described it, the ] of the increase in knowledge which it had brought. Janeway argued that the innate immune system was the real gatekeeper of whether the immune system responded or did not respond. He also argued that the innate immune system used ancient pattern-recognition receptors to make these decisions, recognizing a ] by its unchanging characteristics.


====Danger signals==== ====Danger signals====
In a 1994 article entitled "Tolerance, Danger and the Extended Family", Matzinger went several steps further by laying out the idea that antigen-presenting cells respond to "danger signals" — most notably from cells undergoing injury, stress or "bad cell death" (as opposed to ], controlled ]). 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. 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 ] (controlled ]). 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 occur 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.<ref>{{Cite journal |last=Matzinger |first=Polly |date=April 1994 |title=Tolerance, Danger, and the Extended Family |url=https://www.annualreviews.org/doi/10.1146/annurev.iy.12.040194.005015 |journal=] |language=en |volume=12 |issue=1 |pages=991–1045 |doi=10.1146/annurev.iy.12.040194.005015 |pmid=8011301 |issn=0732-0582}}</ref>


====Scope==== ====Scope====
The danger model is broad, covering topics as diverse as transplantation, maternal/fetal immunity, autoimmunity, cancer treatments, and vaccines, but Matzinger points out that the original model was designed to offer an explanation of how an immune response is triggered and how it ends, but did not offer an explanation of why the immune system responds in different ways to different situations. She has now extended the model to hypothesize that tissues not only send signals alerting the immune system to local damage and stress, but that the tissues also determine the immune response appropriate for that tissue. Before her lab was closed, it was working on experiments to test that hypothesis. She is currently seeking collaborations to continue the research. The danger model is broad, covering topics as diverse as transplantation, maternal/fetal immunity, autoimmunity, cancer treatments, and vaccines. Matzinger argued that prior models failed to explain why immune system responses vary based on the specific threat's location and severity. Prior models also fail to explain how the immune system rejects tumors, induces ], or generates allergic responses.


The danger model has not won universal acceptance. Some immunologists, following Janeway's ideas more directly, believe that the immune response is mainly fueled by innate evolutionarily conserved "pattern recognition receptors" which recognize patterns expressed by microbes such as bacteria, and do not see cell death in the absence of pathogens as a primary driver of immune responses. These ideas however, do not explain how the immune system rejects tumors, induce ], or generate allergy and asthma. 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.{{cn|date=December 2024}}


===Pattern recognition and a tissue-driven immune system=== ===Pattern recognition and a tissue-driven immune system===
] 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 water-filled environment.<ref>{{Cite journal |last1=Seong |first1=Seung-Yong |last2=Matzinger |first2=Polly |date=June 1, 2004 |title=Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses |url=https://www.nature.com/articles/nri1372 |journal=Nature Reviews Immunology |language=en |volume=4 |issue=6 |pages=469–478 |doi=10.1038/nri1372 |pmid=15173835 |s2cid=13336660 |issn=1474-1741}}</ref>
Seong and Matzinger have suggested that the "patterns" that the immune system recognizes on bacteria are not as different from the alarm signals released by damaged cells as one might have thought{{Citation needed|date=February 2018}}. They suggested that, because life evolved in water, the hydrophobic portions of molecules are normally hidden in the internal parts of molecules or other structures (like membranes) and that the sudden exposure of a hydrophobic portion is a sure sign that some injury or damage has occurred. They suggested that these are the most ancient alarm signals, that they are recognized by evolutionarily ancient systems of repair and remodeling, and that the modern immune system piggy-backed on this ancient system. Thus bacteria and other organisms may have very similar alarm systems. They describe these ancient signals as ], or DAMPs.


In a 2013 article in '']'', 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 ] guiding its function and outputs, Matzinger theorizes that microbes may be shown as driving immune system responses.<ref>{{Cite journal |last=Matzinger |first=Polly |date=January 1, 2007 |title=Friendly and Dangerous Signals: Is the Tissue in Control? |url=https://www.nature.com/articles/ni0107-11 |journal=] |language=en |volume=8 |issue=1 |pages=11–13 |doi=10.1038/ni0107-11 |pmid=17179963 |s2cid=6448542 |issn=1529-2916}}</ref> Matzinger argues that DAMPs may explain why ]s 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.
In a 2013 article in ''Nature Immunology'', Matzinger makes a case for what she now views as the most important implication of the danger model: that the tissues of the body are a large part of what drive immune response. She argues that immunologists have had overly simplistic and schematic ideas about immune response because of the limits of their assays, and that organs are likely to induce immune responses that are best-suited to defending the organ from the damage of microbes but also from the damage of the immune system itself. She also asserts that the relationship of the immune system to ] bacteria remains poorly understood but is likely to be important.<ref>{{cite journal|author= Matzinger P|url=https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&list_uids=17179963&cmd=Retrieve&indexed=google |title= Friendly and dangerous signals: is the tissue in control?|date=2013-03-25 |accessdate=2013-08-01|pmid=17179963 |doi=10.1038/ni0107-11 |volume=8 |journal=Nat. Immunol. |pages=11–3}}</ref>

Matzinger argues that the idea of DAMPs may explain why ]s seem to respond both to external and ] signals (while acknowledging controversy over this issue). By emphasizing her theory that the tissues drive the nature of the immune response (i.e., the "what type" rather than the "whether" of immune response), Matzinger describes a dynamic immune system with complex webs of signalling, rather than an immune system that can be explained by a simple and easily reducible set of molecular signals that initiate response or by a small set of cells (e.g., regulatory T cells) that shut it down.


===Challenges to Matzinger's theories=== ===Challenges to Matzinger's theories===
]s have been shown suppressing immune responses, exemplified by the autoimmune ] occurring when the master regulator of these T<sub>reg</sub> cells is dysfunctional.<ref>{{Cite journal |last1=Bruhs |first1=Anika |last2=Proksch |first2=Ehrhardt |last3=Schwarz |first3=Thomas |last4=Schwarz |first4=Agatha |date=2018-03-01 |title=Disruption of the Epidermal Barrier Induces Regulatory T Cells via IL-33 in Mice |journal=Journal of Investigative Dermatology |language=en |volume=138 |issue=3 |pages=570–579 |doi=10.1016/j.jid.2017.09.032 |pmid=29045819 |issn=0022-202X|doi-access=free }}</ref> Matzinger has incorporated T<sub>reg</sub> 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.<ref>{{Cite journal |last=Matzinger |first=Polly |date=January 1, 2007 |title=Friendly and dangerous signals: is the tissue in control? |url=https://www.nature.com/articles/ni0107-11 |journal=Nature Immunology |language=en |volume=8 |issue=1 |pages=11–13 |doi=10.1038/ni0107-11 |pmid=17179963 |s2cid=6448542 |issn=1529-2916}}</ref>
There is now a growing body of work on ] which argues that immune activity is stopped by a special subset of T cells. These ideas challenge several of the key specifics of Matzinger's model. Matzinger argues that these cells are misinterpreted because their functions have not been explored enough. To date (with rare exceptions) these cells have been tested almost exclusively for their ability to suppress highly inflammatory immune response types. The exceptions are illustrative in that they show that regulatory T cells can also act as helper T cells for immune responses in the gut and mucosal tissue. Matzinger argues that their function is to maintain the right kinds of immune responses in the right places, and that they are controlled by signals from the tissues that they protect.


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 destroying some tumors. Second, the danger model explains ] as the result of surgery-induced damage, but this explanation fails to account for greater tolerance of ], the movement of tissue between parts of the same body.<ref>{{Cite journal |last1=Pradeu |first1=Thomas |last2=Cooper |first2=Edwin |date=2012 |title=The danger theory: 20 years later |journal=Frontiers in Immunology |volume=3 |page=287 |doi=10.3389/fimmu.2012.00287 |pmid=23060876 |pmc=3443751 |issn=1664-3224|doi-access=free }}</ref>
A student sitting in an immunology class today will likely hear many phrases coined by Matzinger, such as "professional antigen-presenting-cell", "danger signal", or "]", but will often hear them in the framework of a self/non-self explanation of immunity. Other immunologists have often adapted parts of Matzinger's ideas without adopting the danger model as a theoretical framework. Indeed, in an era of increasingly detailed molecular work, many immunologists simply avoid constructing an alternative broad theory of immune function. One immunologist believes that the immune system is not a single system at all, and is instead a set of mechanisms "cobbled together" by evolution.<ref>{{cite web|author=Russell E. Vance2 |url=http://www.jimmunol.org/cgi/content/full/165/4/1725 |title=Cutting Edge Commentary: A Copernican Revolution? Doubts About the Danger Theory |publisher=Jimmunol.org |date=2000-08-15 |accessdate=2013-08-01}}</ref> If this is true, no single theory can explain the function of the system as a whole. For both of these reasons, Matzinger has had to defend her larger theory, but also has had to defend the value of grand theory itself. She argues that, without a theoretical framework on which to hang the data, much will be missed.


Terms coined by Matzinger, such as "professional antigen-presenting-cell", "danger signal", and "]", 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.<ref>{{cite journal |author=Russell E. Vance2 |url=http://www.jimmunol.org/cgi/content/full/165/4/1725 |title=Cutting Edge Commentary: A Copernican Revolution? Doubts About the Danger Theory |journal=The Journal of Immunology |volume=165 |issue=4 |pages=1725–1728 |publisher=Jimmunol.org |date=2000-08-15 |access-date=2013-08-01 |archive-url=https://web.archive.org/web/20081006223226/http://www.jimmunol.org/cgi/content/full/165/4/1725 |archive-date=2008-10-06 |url-status=live |doi=10.4049/jimmunol.165.4.1725 |pmid=10925247 |doi-access=free }}</ref>
The ] Institute for Immunology and Informatics has named a scholarship for her: the Polly Matzinger Fearless Scientist Scholarship. <ref>{{Cite web|url=https://today.uri.edu/news/uri-biotech-student-awarded-fearless-scientist-scholarship-by-institute-for-immunology-informatics/|title=URI biotech student awarded Fearless Scientist Scholarship by Institute for Immunology & Informatics|website=today.uri.edu|language=en-US|access-date=2018-07-27}}</ref>


===Dog co-author controversy=== ===Dog co-author controversy===
In one of her first publications, a paper for the '']'', she listed a dog as a ].<ref>{{cite journal |doi=10.1084/jem.148.1.84 |pmid=78964 |title=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 |author=Polly Matzinger |author2=Galadriel Mirkwood |journal=] |year=1978 |volume=148 |issue=1 |pages=84&ndash;92 |pmc=2184911}}{{open access}}</ref> Ted Anton described the decision in his book ''Bold Science'': "Refusing to write in the usual scientific passive voice ('steps were taken') and too insecure to write in the first person ('I took the steps'), she instead invented coauthor": her ], Galadriel Mirkwood.<ref>. New York: WH Freeman, 2000.</ref> Once the deception was discovered, papers on which she was a major author were barred from the journal until the editor died and was replaced by another.<ref>{{Cite web|url=https://www.the-scientist.com/tue-01-may-2001-00-00-00-gmt/scientific-sins-51676|title=Scientific Sins|website=The Scientist Magazine®|language=en|access-date=2018-07-27}}</ref> In 1978, Matzinger published her fourth paper in the '']'', listing her ], Galadriel Mirkwood, as a ] to write in a third-person active voice.<ref>{{cite journal |doi=10.1084/jem.148.1.84 |pmid=78964 |title=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 |author=Polly Matzinger |author2=Galadriel Mirkwood |journal=] |year=1978 |volume=148 |issue=1 |pages=84&ndash;92 |pmc=2184911}}{{open access}}</ref> Upon identifying this, she was banned from publishing in the journal.<ref>{{Cite book |last=Anton |first=Ted |title=Bold Science: Seven Scientists Who Are Changing Our World |publisher=] |year=2000 |isbn=9780716735120}}</ref>

== Awards ==
At the 1986 ], Polly Matzinger won the Award for Special Excellence in Educational Films for the German translation of ''Immunity: The Inside Story''. In 1996, she was inducted as an honorary lifetime member of the Scandinavian Society of Immunology. In 2002, '']'' magazine recognized Matzinger as one of the fifty most important women in science.<ref name="Svitil">{{cite news |last1=Svitil |first1=Kathy |date=13 November 2002 |title=The 50 Most Important Women in Science |publisher=Discover |url=http://discovermagazine.com/2002/nov/feat50/ |url-status=live |access-date=1 May 2019 |archive-url=https://web.archive.org/web/20190511023736/http://discovermagazine.com/2002/nov/feat50/ |archive-date=11 May 2019}}</ref> In 2003, she received an ] from ]. In 2008, she was listed as a "Highly Cited" research among the top 1% of citations for her field on the ].<ref name=":3" />

Since 2009, the biotechnology company EpiVax has funded the Polly Matzinger Fearless Scientist Scholarship for women scientists at the ]'s Institute for Immunology & Informatics that overcome challenges.<ref>{{Cite web |last= |date=2009-11-13 |title=Polly Matzinger Fearless Scientist Award |url=https://epivax.com/news/polly-matzinger-fearless-scientist-award |access-date=2023-01-10 |website=EpiVax |language=en-US}}</ref>


==Publications== ==Publications==
* {{cite journal | author = Matzinger P., Mirkwood G. | year = 1978 | title = 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 | url = http://www.jem.org/cgi/content/abstract/148/1/84 | journal = Journal of Experimental Medicine | volume = 148 | issue = 1| pages = 84–92 | doi=10.1084/jem.148.1.84 | pmid=78964 | pmc=2184911}} * {{cite journal | author = Matzinger P., Mirkwood G. | year = 1978 | title = 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 | journal = Journal of Experimental Medicine | volume = 148 | issue = 1| pages = 84–92 | doi=10.1084/jem.148.1.84 | pmid=78964 | pmc=2184911}}
* Lassila, O., Vainio, O. and Matzinger, P. (1988). Can ]s turn on virgin T cells? ''Nature'', '''334''', 253-255. (the article in which "professional antigen presenting cells" were first named) * Lassila, O., Vainio, O. and Matzinger, P. (1988). Can ]s turn on virgin T cells? ''Nature'', '''334''', 253–255. (the article in which "professional antigen presenting cells" were first named)
* {{cite journal | author = Fuchs E., Matzinger P. B. | year = 1992 | title = B cells turn off virgin but not ]. | url = | journal = Science | volume = 258 | issue = | pages = 1156–1159 | doi=10.1126/science.1439825}} * {{cite journal | author = Fuchs E., Matzinger P. B. | year = 1992 | title = B cells turn off virgin but not memory T cells. | url = https://zenodo.org/record/1230938| journal = Science | volume = 258 | issue = 5085| pages = 1156–1159 | doi=10.1126/science.1439825| pmid = 1439825 | bibcode = 1992Sci...258.1156F }}
* {{cite journal | author = Matzinger P | year = 1994 | title = Tolerance, Danger, and the Extended Family | pmid = 8011301 | journal = Annual Review of Immunology | volume = 12 | issue = | pages = 991–1045 | doi=10.1146/annurev.iy.12.040194.005015}} * {{cite journal | author = Matzinger P | year = 1994 | title = Tolerance, Danger, and the Extended Family | pmid = 8011301 | journal = Annual Review of Immunology | volume = 12 | pages = 991–1045 | doi=10.1146/annurev.iy.12.040194.005015}}
* {{cite journal |author1=Ridge J.P. |author2=Fuchs E. |author3=Matzinger P. | year = 1996 | title = Neonatal tolerance revisited: turning on newborn T cells with ]s. | url = | journal = Science | volume = 271 | issue = | pages = 1723–1726 | doi=10.1126/science.271.5256.1723}} * {{cite journal |author1=Ridge J.P. |author2=Fuchs E. |author3=Matzinger P. | year = 1996 | title = Neonatal tolerance revisited: turning on newborn T cells with dendritic cells. | url = https://zenodo.org/record/1231066| journal = Science | volume = 271 | issue = 5256| pages = 1723–1726 | doi=10.1126/science.271.5256.1723|pmid=8596932 |bibcode=1996Sci...271.1723R |s2cid=42548782 }}
* {{cite journal |author1=Ridge J.P. |author2=Di Rosa F. |author3=Matzinger P. | year = 1998 | title = A conditioned dendritic cell can be a temporal bridge between a CD4+ ] and a T- killer cell | url = | journal = Nature | volume = 393 | issue = | pages = 474–478 }} * {{cite journal |author1=Ridge J.P. |author2=Di Rosa F. |author3=Matzinger P. | year = 1998 | title = A conditioned dendritic cell can be a temporal bridge between a CD4+ T helper cell and a T- killer cell | journal = Nature | volume = 393 | issue = 6684| pages = 474–478 |doi=10.1038/30989 |pmid=9624003 |s2cid=4427685 }}
* {{cite journal |author1=Gallucci S. |author2=Lolkema M. |author3=Matzinger P. | year = 1999 | title = Natural adjuvants: Endogenous activators of dendritic cells | url = | journal = Nature Medicine | volume = 5 | issue = | pages = 1249–1255 | doi=10.1038/15200 | pmid=10545990}} * {{cite journal |author1=Gallucci S. |author2=Lolkema M. |author3=Matzinger P. | year = 1999 | title = Natural adjuvants: Endogenous activators of dendritic cells | journal = Nature Medicine | volume = 5 | issue = 11| pages = 1249–1255 | doi=10.1038/15200 | pmid=10545990|s2cid=29090284 }}
* {{cite journal | author = Matzinger P | year = 2002 | title = The Danger Model: A Renewed Sense of Self | url = http://www.fiu.edu/~ci/danger.pdf | format = PDF | journal = Science | volume = 296 | issue = | pages = 301–305 | doi=10.1126/science.1071059 | pmid=11951032}} * {{cite journal | author = Matzinger P | year = 2002 | title = The Danger Model: A Renewed Sense of Self | url = http://www.fiu.edu/~ci/danger.pdf | journal = Science | volume = 296 | issue = 5566| pages = 301–305 | doi=10.1126/science.1071059 | pmid=11951032| bibcode = 2002Sci...296..301M | citeseerx = 10.1.1.127.558 | s2cid = 13615808 }}
* {{cite journal | author = Seong S., Matzinger P. | year = 2004 | title = Hydrophobicity, an ancient Damage-associated Molecular Pattern that initiates Innate Immune Responses | url = | journal = Nature Reviews Immunology | volume = 4 | issue = | pages = 469–78 | doi=10.1038/nri1372 | pmid=15173835}} * {{cite journal | author = Seong S., Matzinger P. | year = 2004 | title = Hydrophobicity, an ancient Damage-associated Molecular Pattern that initiates Innate Immune Responses | journal = Nature Reviews Immunology | volume = 4 | issue = 6| pages = 469–78 | doi=10.1038/nri1372 | pmid=15173835| s2cid = 13336660 }}
* {{cite journal | author = Matzinger P | year = 2007 | title = Friendly and dangerous signals: is the tissue in control? | url = https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&list_uids=17179963&cmd=Retrieve&indexed=google | journal = Nature Immunology | volume = 8 | issue = | pages = 11–13 | pmid = 17179963 | doi=10.1038/ni0107-11}} * {{cite journal | author = Matzinger P | year = 2007 | title = Friendly and dangerous signals: is the tissue in control? | journal = Nature Immunology | volume = 8 | issue = 1 | pages = 11–13 | pmid = 17179963 | doi=10.1038/ni0107-11| s2cid = 6448542 | url = https://zenodo.org/record/1233431 }}
* {{cite journal |vauthors=Matzinger P, Kamala T | year = 2011 | title = Tissue-based class control: the other side of tolerance | url = https://zenodo.org/record/1233542/files/article.pdf| journal = Nature Reviews Immunology | volume = 11 | issue = | pages = 221–30 | doi=10.1038/nri2940}} * {{cite journal |vauthors=Matzinger P, Kamala T | year = 2011 | title = Tissue-based class control: the other side of tolerance | url = https://zenodo.org/record/1233542| journal = Nature Reviews Immunology | volume = 11 | issue = 3| pages = 221–30 | doi=10.1038/nri2940| pmid = 21350581 | s2cid = 10809131 }}
* {{cite journal |author1=Perez-Diez Ainhoa |author2=Joncker Nathalie T. |author3=Choi Kyungho |author4=Chan William F. N. |author5=Anderson Colin C. |author6=Lantz Olivier |author7=Matzinger Polly | year = 2007 | title = CD4 cells can be more efficient at tumor rejection than CD8 cells | url = http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/12/5346/ | journal = Blood | volume = 109 | issue = | pages = 5346–5354 | doi=10.1182/blood-2006-10-051318|pmc=1890845 }} * {{cite journal |author1=Perez-Diez Ainhoa |author2=Joncker Nathalie T. |author3=Choi Kyungho |author4=Chan William F. N. |author5=Anderson Colin C. |author6=Lantz Olivier |author7=Matzinger Polly | year = 2007 | title = CD4 cells can be more efficient at tumor rejection than CD8 cells | journal = Blood | volume = 109 | issue = 12| pages = 5346–5354 | doi=10.1182/blood-2006-10-051318|pmc=1890845 | pmid=17327412}}


==Films== ==Films==
*''Immunity: the inside story''. Matzinger P and André Trauneker (1986) (video, 13 min). Award-winning animated film for lay people describing the events involved in clearing an ]. Translated into German, French, Spanish. ] studio, ] *''Immunity: the inside story''. Matzinger P and André Trauneker (1986) (video, 13 min). Award-winning animated film for lay people describing the events involved in clearing an ]. Translated into German, French, Spanish. ] studio, ]
*''A quick look at tissue rejection''. Matzinger P. (1991) (Video, 2 min). Animated film for lay people describing the events that result in rejection of a ]. Commissioned by the ] for a meeting of television producers. NIH special events department and ] *''A quick look at tissue rejection''. Matzinger P. (1991) (Video, 2 min). Animated film for lay people describing the events that result in rejection of a ]. Commissioned by the ] for a meeting of television producers. NIH special events department and ]
*'']''.<ref>{{cite web|url=http://www.strange-attractions.com/films/death-by-design/ |title=Death By Design |publisher=Strange Attractions |date= |accessdate=2013-10-17}}</ref> Peter Friedman and Jean-François Brunet (1995) (Film, 73 minutes). Award-winning film on ] cell death that features the work of six scientists. P Matzinger, ], M Raff, P Goldstein, KM Debatin, R Horowitz among others *'']''.<ref>{{cite web |url=http://www.strange-attractions.com/films/death-by-design/ |title=Death By Design |publisher=Strange Attractions |access-date=2013-10-17 |archive-url=https://web.archive.org/web/20131017195012/http://www.strange-attractions.com/films/death-by-design/ |archive-date=2013-10-17 |url-status=live }}</ref> Peter Friedman and Jean-François Brunet (1995) (Film, 73 minutes). Award-winning film on ] cell death that features the work of six scientists. P Matzinger, ], M Raff, P Golstein, KM Debatin, R Horowitz among others
*''Turned on by Danger''. ] (1997) (Film, 60 minutes). A ] program made for ] featuring and delineating the ]. *''Turned on by Danger''. ] (1997) (Film, 60 minutes). A ] program made for ] featuring and delineating the ].
*''Microbe Invasion''. ] (2001) (Film, 60 minutes). A program describing the interrelationship between ] 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 ] within the body. ] *''Microbe Invasion''. ] (2001) (Film, 60 minutes). A program describing the interrelationship between ] 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 ] within the body. ]


==References== ==References==
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==External links== ==External links==
* , (Ambling Brook Farm) * , (Ambling Brook Farm)
* in the '']'' * in the '']''
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* in '']'' magazine
* in '']'' * in '']''
* {{IMDb title|118947|title=Death by Design/The Life and Times of Life and Times}} * {{IMDb title|118947|title=Death by Design/The Life and Times of Life and Times}}
* {{ResearchGate|Polly_Matzinger}}
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Latest revision as of 13:26, 13 December 2024

French-born American immunologist
Polly Matzinger
Born (1947-07-21) July 21, 1947 (age 77)
La Seyne, France
Alma materUniversity of California, Irvine (BS)
University of California, San Diego (PhD)
Known forDanger model
Scientific career
FieldsImmunology
InstitutionsNational Institute of Allergy and Infectious Diseases

Polly Celine Eveline Matzinger (born July 21, 1947) is a French-born immunologist who proposed the danger model theory of how the immune system works.

Early years

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 U.S. with her sister, Marjolaine, and parents. Her prior jobs included being a bass jazz musician, carpenter, dog trainer, waitress, and Playboy Bunny. She finished her bachelor's of science in biology at the University of California, Irvine in 1976, and doctorate in biology at the University of California, San Diego in 1979. She then did four years of postdoctoral work at the University of Cambridge and was a scientist at the Basel Institute for Immunology for six years before working at the National Institutes of Health in Bethesda, Maryland.

Ghost Lab at NIAID

Matzinger is chief of the T-Cell Tolerance and Memory Section at the U.S. National Institute of Allergy and Infectious Diseases (NIAID). 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 chaos theory. In 2013, while reorganizing the Laboratory of Cellular and Molecular Immunology, NIAID transferred Matzinger's section to the Laboratory of Immunogenetics.

In 2015, Matzinger recorded an eight-part series on the danger model of the immune system, covering transplant rejection, tumors, autoimmunity, T cells, parasites, and alarmins.

Research

The danger model

The Self/Non-self Model proposed by Macfarlane Burnet and Frank Fenner in 1949 faced challenges in the late 1980s as immunologists recognized that T cells depend on antigen-presenting cells showcasing materials and sending co-stimulatory signals. Driven by the writings of Thomas Kuhn on paradigm shifts in science, Charles Janeway 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 pathogen by its unchanging characteristics.

Danger signals

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 apoptosis (controlled cell death). 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 occur 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.

Scope

The danger model is broad, covering topics as diverse as transplantation, maternal/fetal immunity, autoimmunity, cancer treatments, and vaccines. Matzinger argued that prior models failed to explain why immune system responses vary based on the specific threat's location and severity. Prior models also fail to explain how the immune system rejects tumors, induces autoimmune diseases, or generates allergic responses.

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.

Pattern recognition and a tissue-driven immune system

Seung-Yong Seong 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 water-filled environment.

In a 2013 article in Nature Immunology, 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 microbiome guiding its function and outputs, Matzinger theorizes that microbes may be shown as driving immune system responses. Matzinger argues that DAMPs may explain why toll-like receptors 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.

Challenges to Matzinger's theories

Regulatory T cells have been shown suppressing immune responses, exemplified by the autoimmune IPEX syndrome occurring when the master regulator of these Treg cells is dysfunctional. Matzinger has incorporated Treg 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.

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 destroying some tumors. Second, the danger model explains transplant rejection as the result of surgery-induced damage, but this explanation fails to account for greater tolerance of autotransplantation, the movement of tissue between parts of the same body.

Terms coined by Matzinger, such as "professional antigen-presenting-cell", "danger signal", and "DAMPs", 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.

Dog co-author controversy

In 1978, Matzinger published her fourth paper in the Journal of Experimental Medicine, listing her Afghan Hound, Galadriel Mirkwood, as a coauthor to write in a third-person active voice. Upon identifying this, she was banned from publishing in the journal.

Awards

At the 1986 Köln Film Festival, Polly Matzinger won the Award for Special Excellence in Educational Films for the German translation of Immunity: The Inside Story. In 1996, she was inducted as an honorary lifetime member of the Scandinavian Society of Immunology. In 2002, Discover magazine recognized Matzinger as one of the fifty most important women in science. In 2003, she received an honorary doctorate from Hasselt University. In 2008, she was listed as a "Highly Cited" research among the top 1% of citations for her field on the Web of Science.

Since 2009, the biotechnology company EpiVax has funded the Polly Matzinger Fearless Scientist Scholarship for women scientists at the University of Rhode Island's Institute for Immunology & Informatics that overcome challenges.

Publications

Films

References

  1. ^ Oakes, Elizabeth H. (2014-05-14). A to Z of STS Scientists. Infobase Publishing. ISBN 9781438109251.
  2. Cooper, Glenda (April 16, 1997). "Clever Bunny". The Independent. Archived from the original on 2018-07-27. Retrieved 2018-07-27.
  3. ^ "Polly Matzinger: De conejita playboy a paradigma de la inmunología". Procrastina Fácil (in European Spanish). 2018-04-29. Archived from the original on 2018-07-27. Retrieved 2018-07-27.
  4. DREIFUS, CLAUDIA (June 16, 1998). "A Conversation With Polly Matzinger; Blazing an Unconventional Trail to a New Theory of Immunity". The New York Times. Archived from the original on 18 January 2015. Retrieved 19 Jan 2015.
  5. ^ Oakes, Elizabeth H. (2007). Encyclopedia of World Scientists. Infobase Publishing. ISBN 9781438118826.
  6. ^ "Polly Matzinger, Ph.D." National Institute of Allergy and Infectious Disease. July 19, 2022. Retrieved 2023-01-10.
  7. Matzinger, Polly (2015-09-22), Immunology Course based on the Danger Model: Session 1, National Institutes of Health, retrieved 2023-01-10
  8. Matzinger, Polly (April 1994). "Tolerance, Danger, and the Extended Family". Annual Review of Immunology. 12 (1): 991–1045. doi:10.1146/annurev.iy.12.040194.005015. ISSN 0732-0582. PMID 8011301.
  9. Seong, Seung-Yong; Matzinger, Polly (June 1, 2004). "Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses". Nature Reviews Immunology. 4 (6): 469–478. doi:10.1038/nri1372. ISSN 1474-1741. PMID 15173835. S2CID 13336660.
  10. Matzinger, Polly (January 1, 2007). "Friendly and Dangerous Signals: Is the Tissue in Control?". Nature Immunology. 8 (1): 11–13. doi:10.1038/ni0107-11. ISSN 1529-2916. PMID 17179963. S2CID 6448542.
  11. Bruhs, Anika; Proksch, Ehrhardt; Schwarz, Thomas; Schwarz, Agatha (2018-03-01). "Disruption of the Epidermal Barrier Induces Regulatory T Cells via IL-33 in Mice". Journal of Investigative Dermatology. 138 (3): 570–579. doi:10.1016/j.jid.2017.09.032. ISSN 0022-202X. PMID 29045819.
  12. Matzinger, Polly (January 1, 2007). "Friendly and dangerous signals: is the tissue in control?". Nature Immunology. 8 (1): 11–13. doi:10.1038/ni0107-11. ISSN 1529-2916. PMID 17179963. S2CID 6448542.
  13. Pradeu, Thomas; Cooper, Edwin (2012). "The danger theory: 20 years later". Frontiers in Immunology. 3: 287. doi:10.3389/fimmu.2012.00287. ISSN 1664-3224. PMC 3443751. PMID 23060876.
  14. Russell E. Vance2 (2000-08-15). "Cutting Edge Commentary: A Copernican Revolution? Doubts About the Danger Theory". The Journal of Immunology. 165 (4). Jimmunol.org: 1725–1728. doi:10.4049/jimmunol.165.4.1725. PMID 10925247. Archived from the original on 2008-10-06. Retrieved 2013-08-01.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  15. Polly Matzinger; Galadriel Mirkwood (1978). "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". Journal of Experimental Medicine. 148 (1): 84–92. doi:10.1084/jem.148.1.84. PMC 2184911. PMID 78964.Open access icon
  16. Anton, Ted (2000). Bold Science: Seven Scientists Who Are Changing Our World. W. H. Freeman and Company. ISBN 9780716735120.
  17. Svitil, Kathy (13 November 2002). "The 50 Most Important Women in Science". Discover. Archived from the original on 11 May 2019. Retrieved 1 May 2019.
  18. "Polly Matzinger Fearless Scientist Award". EpiVax. 2009-11-13. Retrieved 2023-01-10.
  19. "Death By Design". Strange Attractions. Archived from the original on 2013-10-17. Retrieved 2013-10-17.

External links

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