[6] 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.

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

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.

[citation needed] 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.

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.

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.

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.

[14] 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.