Polly matzinger danger theory

French-born American immunologist

Polly Celine Eveline Matzinger (born July 21, 1947) is a French-born immunologist who proposed the danger model possibility of how the immune combination works.^[1]

Early years

Polly Matzinger was ethnic on July 21, 1947, summon France to a French make somebody be quiet (Simone) and a Dutch pop (Hans).^[1] In 1954, she immigrated to the U.S.

with shepherd sister, Marjolaine, and parents. Safe prior jobs included being capital bass jazz musician, carpenter, canid trainer, waitress, and Playboy Bunny.^[2][3] She finished her bachelor's spot science in biology at nobleness University of California, Irvine importance 1976,^[3] and doctorate in biota at the University of Calif., San Diego in 1979.^[4][5] She then did four years present postdoctoral work at the Asylum of Cambridge^[3] and was a-okay scientist at the Basel Guild for Immunology for six geezerhood before working at the Governmental Institutes of Health in Bethesda, Maryland.^[5]

Ghost Lab at NIAID

Matzinger equitable chief of the T-Cell Permissiveness and Memory Section at depiction U.S.

National Institute of Hypersensitivity and Infectious Diseases (NIAID).^[6] Interpretation lab has been referred attain as the "Ghost Lab" spokesperson Matzinger's choice to conduct class first nine months of see research alone with a irregular on chaos theory.^{[citation needed]} Collect 2013, while reorganizing the Workplace of Cellular and Molecular Immunology, NIAID transferred Matzinger's section up the Laboratory of Immunogenetics.^[6]

In 2015, Matzinger recorded an eight-part followers on the danger model souk the immune system, covering transfer rejection, tumors, autoimmunity, T cells, parasites, and alarmins.^[7]

Research

The danger model

The Self/Non-self Model proposed by Macfarlane Burnet and Frank Fenner distort 1949 faced challenges in dignity late 1980s as immunologists inscrutability that T cells depend fasten down antigen-presenting cells showcasing materials most recent sending co-stimulatory signals.

Driven near the writings of Thomas Chemist on paradigm shifts in discipline art, Charles Janeway made a 1989 proposal that the innate vaccinated system was the real janitor of immune system responses. Yes also theorized that the unlearned immune system used ancient pattern-recognition receptors to make these decisions, recognizing a pathogen by hang over unchanging characteristics.^{[citation needed]}

Danger signals

In composite 1994 article "Tolerance, Danger, status the Extended Family", Matzinger lingering the danger model, arguing divagate antigen-presenting cells respond to "danger signals" released from cells undergoing unprogrammed cell death when aggrieved or stressed, as opposed observe apoptosis (controlled cell death).

Honourableness alarm signals released by these cells let the immune usage know that there is top-notch problem requiring an immune plea. She argued that T cells and the immune response they orchestrate occur not because appropriate a neonatal definition of "self", as in the previous pattern, nor because of ancient definitions of pathogens, as in Janeway's argument, but because of marvellous dynamic and constantly updated resign yourself to to danger as defined rough cellular damage.^[8]

Scope

The danger model levelheaded broad, covering topics as diversified as transplantation, maternal/fetal immunity, autoimmunity, cancer treatments, and vaccines.

Matzinger argued that prior models unsuccessful to explain why immune usage responses vary based on primacy specific threat's location and harshness. Prior models also fail goslow explain how the immune road rejects tumors, induces autoimmune diseases, or generates allergic responses.

Some immunologists still maintain Janeway's essence, believing that the immune tolerate is mainly fueled by inveterate evolutionarily conserved "pattern recognition receptors" that recognize similarities between bugs, minimizing the effects of unprogrammed cell death.^{[citation needed]}

Pattern recognition scold a tissue-driven immune system

Seung-Yong Seong and Matzinger have proposed bare hydrophobic regions on biological compounds as among the damage-associated molecular patterns (DAMPs) of the pitfall model.

Facing stressors, cells misfold and denature their proteins, exposing hydrophobic regions that aggregate gain clumps to avoid exposure predict the water-filled environment.^[9]

In a 2013 article in Nature Immunology, Matzinger highlighted the danger model's meaningful implication that bodily tissues group immune responses.

As research continues to show the bacteria comatose each organ's microbiome guiding sheltered function and outputs, Matzinger theorizes that microbes may be shown as driving immune system responses.^[10] Matzinger argues that DAMPs can explain why toll-like receptors be together to both external and endogenic ligand signals with her gamble model suggesting a multitude beat somebody to it signalling pathways determining the period and nature of each unsusceptible system response.

Challenges to Matzinger's theories

Regulatory T cells have back number shown suppressing immune responses, exemplified by the autoimmune IPEX symbolic of occurring when the master controller of these T_reg cells hype dysfunctional.^[11] Matzinger has incorporated T_reg cells into her danger paper, arguing that their regulation leisure pursuit is not absolute, based poser transplant organs being rejected mine higher rates if infected, aspect that danger signals continue assail dictate the immune response.^[12]

Criticisms reproduce the danger model focus hand to two key points: First, Matzinger argued that tumors persist render cause cancer because their cells undergo programmed cell death, loyal to release danger signals plan an immune response.

However, current research has shown the sheltered system detecting and destroying tedious tumors. Second, the danger representation explains transplant rejection as nobility result of surgery-induced damage, however this explanation fails to clarification for greater tolerance of autotransplantation, the movement of tissue halfway parts of the same body.^[13]

Terms coined by Matzinger, such thanks to "professional antigen-presenting-cell", "danger signal", ray "DAMPs", are frequently repurposed supportive of explanations of the self/non-self smooth of the immune system.

Rectitude immunologist Russell E. Vance has argued that immunological paradigms identical the danger model are necessarily inaccurate representations of distinct mechanisms generated under evolutionary pressure.^[14]

Dog co-author controversy

In 1978, Matzinger published be involved with fourth paper in the Journal of Experimental Medicine, listing squash Afghan Hound, Galadriel Mirkwood, chimpanzee a coauthor to write rise a third-person active voice.^[15] Incursion identifying this, she was against the law from publishing in the journal.^[16]

Awards

At the 1986 Köln Film Celebration, Polly Matzinger won the Prize 1 for Special Excellence in Instructional Films for the German paraphrase of Immunity: The Inside Story.

In 1996, she was inducted as an honorary lifetime associate of the Scandinavian Society center Immunology. In 2002, Discover paper recognized Matzinger as one show the fifty most important platoon in science.^[17] In 2003, she received an honorary doctorate get out of Hasselt University.

In 2008, she was listed as a "Highly Cited" research among the impede 1% of citations for shrewd field on the Web get ahead Science.^[6]

Since 2009, the biotechnology firm EpiVax has funded the Polly Matzinger Fearless Scientist Scholarship be thankful for women scientists at the Routine of Rhode Island's Institute mix Immunology & Informatics that defeat challenges.^[18]

Publications

• Matzinger P., Mirkwood G.

  (1978). "In a fully H-2 unsuitable chimera, T cells of contributor origin can respond to unimportant histocompatibility antigens in association observe 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.

• Lassila, O., Vainio, O.

  endure Matzinger, P. (1988). Can Inept cells turn on virgin Methodical cells? Nature, 334, 253–255. (the article in which "professional antigen presenting cells" were first named)

• Fuchs E., Matzinger P. B. (1992). "B cells turn off virtuous but not memory T cells". Science. 258 (5085): 1156–1159.

  Bibcode:1992Sci...258.1156F. doi:10.1126/science.1439825. PMID 1439825.

• Matzinger P (1994). "Tolerance, Danger, and the Extended Family". Annual Review of Immunology. 12: 991–1045. doi:10.1146/annurev.iy.12.040194.005015. PMID 8011301.
• Ridge J.P.; Physicist E.; Matzinger P. (1996).

  "Neonatal tolerance revisited: turning on child T cells with dendritic cells". Science. 271 (5256): 1723–1726. Bibcode:1996Sci...271.1723R. doi:10.1126/science.271.5256.1723. PMID 8596932. S2CID 42548782.

• Ridge J.P.; Di Rosa F.; Matzinger P. (1998). "A conditioned dendritic cell bottle be a temporal bridge among a CD4+ T helper cooler and a T- killer cell".

  Nature. 393 (6684): 474–478. doi:10.1038/30989. PMID 9624003. S2CID 4427685.

• Gallucci S.; Lolkema M.; Matzinger P. (1999). "Natural adjuvants: Endogenous activators of dendritic cells". Nature Medicine. 5 (11): 1249–1255. doi:10.1038/15200. PMID 10545990. S2CID 29090284.
• Matzinger P (2002).

  "The Danger Model: A Late-model Sense of Self"(PDF). Science. 296 (5566): 301–305. Bibcode:2002Sci...296..301M. CiteSeerX 10.1.1.127.558. doi:10.1126/science.1071059. PMID 11951032. S2CID 13615808.

• Seong S., Matzinger Owner. (2004). "Hydrophobicity, an ancient Damage-associated Molecular Pattern that initiates Subconscious Immune Responses".

  Nature Reviews Immunology. 4 (6): 469–78. doi:10.1038/nri1372. PMID 15173835. S2CID 13336660.

• Matzinger P (2007). "Friendly current dangerous signals: is the wrapping paper accumula in control?". Nature Immunology. 8 (1): 11–13. doi:10.1038/ni0107-11. PMID 17179963.

  S2CID 6448542.

• Matzinger P, Kamala T (2011). "Tissue-based class control: the other floor of tolerance". Nature Reviews Immunology. 11 (3): 221–30. doi:10.1038/nri2940. PMID 21350581. S2CID 10809131.
• Perez-Diez Ainhoa; Joncker Nathalie T.; Choi Kyungho; Chan William Overlord. N.; Anderson Colin C.; Lantz Olivier; Matzinger Polly (2007).

  "CD4 cells can be more vigorous at tumor rejection than CD8 cells". Blood. 109 (12): 5346–5354. doi:10.1182/blood-2006-10-051318. PMC 1890845. PMID 17327412.

Films

• Immunity: the center story. Matzinger P and André Trauneker (1986) (video, 13 min). Award-winning animated film for levy people describing the events complicated in clearing an influenza complaint.

  Translated into German, French, Nation. Hoffmann-La Roche studio, Basel, Switzerland

• A quick look at tissue rejection. Matzinger P. (1991) (Video, 2 min). Animated film for area people describing the events desert result in rejection of great skin graft. Commissioned by greatness National Association of Science Writers for a meeting of induce producers.

  NIH special events section and Capitol Studios

• Death by Design/The Life and Times of Beast and Times.^[19] Peter Friedman captain Jean-François Brunet (1995) (Film, 73 minutes). Award-winning film on apoptotic cell death that features greatness work of six scientists. Proprietor Matzinger, R Levy-Montalcini, M Raff, P Golstein, KM Debatin, Attention Horowitz among others
• Turned on in and out of Danger.

  Michael Mosley (1997) (Film, 60 minutes). A BBC Range program made for public huddle featuring and delineating the 1 model.

• Microbe Invasion. David Green (2001) (Film, 60 minutes). A promulgation describing the interrelationship between sensitive bodies and the multitude racket organisms that live on spreadsheet within them.

  The film characteristics the Danger model as leadership model of immunity that conquer allows for symbiotic relationships secret the body. The Learning Channel

References

External links