Polly Matzinger

Polly Matzinger is an iconoclastic scientist who proposed a novel explanation of how the immune system works, called the 'danger model'.

The self-non-self model, the predominant model in immunology since the 1950s, 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--and that the T-cell response depends on whether the other cell (known as antigen-presenting cells) is sending activation signals to the T-cells. In 1989, Charles Janeway proposed that the old model had reached its end, and 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 pathogen by its unchanging characteristics.

In a 1994 article entitled "Tolerance, Danger and the Extended Family", Matzinger responded to Janeway's idea but went several steps further by laying out the idea that antigen-presenting cells respond to "danger signals" — most notably, "bad cell death" which suggests a problem requiring immune response. She argued that T-cells and the immune response they orchestrate happens not based on a neonatal definition of "self", as in the previous model, and not based on ancient definitions of pathogens, as in Janeway's argument, but on a dynamic and constantly-updated response to danger as defined by cellular damage.

Polly Matzinger is now a section head at the National Institute of Allergy and Infectious Diseases (her lab is called the Ghost Lab) and her Danger Model has become an important reference point for many immunologists and an inspiration to many students of immunology; it has undergone various modifications since then, which can be seen in her more recent theoretical writing.

The Danger Model has not won universal acceptance. Some immunologists, following Janeway's ideas more directly, believe that the immune response is mainly fuelled by innate evolutionarily-conserved "pattern recognition receptors" and do not see cell death in the absence of pathogens as a primary driver of immune response. There is also a growing body of work on "regulatory T-cells" 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. And a student sitting in an immunology class today will likely hear many phrases coined by Matzinger (like "professional antigen-presenting-cell" or "danger signal") but will often hear them in the framework of a self-non-self explanation of immunity.

Indeed, in an era of increasingly detailed molecular work, many immunologists simply avoid constructing an alternative broad theory of immune function. In that sense, Matzinger has both had to defend her larger theory, and also has had to defend the value of grand theory itself.

The Danger Model is quite broad, but Matzinger points out that although it offers an explanation of how an immune response is triggered and how it ends, it does not offer an explanation of why the immune system responds in different ways in different situations. She hypothesizes that tissues send signals to the immune system that determine the immune response appropriate for that tissue, and her lab is now working on experiments to test that hypothesis.

Matzinger has long been well-known for her biography: for instance, in one of her first publications, she coauthored a paper with Galadriel Mirkwood for the Journal of Experimental Medicine. The journal barred Matzinger for 15 years "until the editor died" since it turned out that the coauthor was her Afghan Hound which according to her was as much involved in research as many other coauthors. When travelling for scientific talks, she now customarily dyes her hair green for the occasion. She took to science from an unusual background career path which included stints as a Playboy Bunny at a Playboy Club in Denver, a jazz musician, and a bar waitress. Although no dogs have been coauthors of any of her recent papers, she is an avid sheepdog trainer.

To many she stands as a symbol of the scientific spirit and its openness.

External links

• http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8011301&query_hl=2
• http://www.fiu.edu/~ci/danger.pdf (Science article from 2002--an update of her thinking since 1994)
• http://bjo.bmjjournals.com/cgi/content/full/81/11/934
• http://www2.mni.uwo.ca/3m/Previous%20Speakers/Matzinger.html
• http://www.the-scientist.com/yr2003/may/upfront10_030505.html
• http://www.arthritis.org/resources/arthritistoday/1999_archives/1999_03_04polly.asp
• http://www.jem.org/cgi/content/abstract/148/1/84