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Polly Matzinger 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 heading to the National Institutes of Health in Bethesda, Maryland.

THE REAL FUNCTION OF THE IMMUNE SYSTEM or.

In , Polly Matzinger recorded an eight-part series on the danger model of the immune system, covering transplant rejection, tumors, autoimmunity, T cells, parasites, and alarmins. Polly Matzinger theorized that the innate immune system used ancient pattern-recognition receptors to make these decisions, recognizing a pathogen by its unchanging characteristics.

Polly Matzinger 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. Polly Matzinger argues that prior models failed to explain why immune system responses vary based on the specific threat's location and severity.

Seung-Yong Seong and Polly Matzinger have proposed exposed hydrophobic regions on biological compounds as among the damage-associated molecular patterns of the danger model.

Born Polly Matzinger followed a rather unusual path into science.

Polly 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, Polly Matzinger argued that tumors persist to cause cancer because their cells undergo programmed cell death, failing to release danger signals for an immune response.

In , Polly 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.