Perspectives of the Danger/Injury Model in Immunology

Abstract

The short prologue of Volume 2 of the book is intended to remind us that the danger/injury model, proposed 25 years ago, is slowly outdated in light of continuously advancing scientific research and, thus, is worth modifying. As an example of steadily growing knowledge, a glance is taken to a holistic view of the universal defense system, as it can be discussed today. The evolutionarily developed defense program is dominated by cell stress/tissue injury-induced damage-associated molecular patterns (DAMPs), which are sensed/recognized by pattern recognition molecules expressed by cells of the innate immune system to trigger life-sustaining/life-saving defense responses. Four major mammalian defense responses are distinguished: (1) the innate immune response in terms of an inflammatory response; (2) the adaptive immune response in terms of a specific T- and B-cell response; (3) the mechanically induced innate response in terms of a conversion of mechanical forces into physiological responses; and (4) the fight-or-flight response in terms of a rapid physical response in the face of danger. Further, a short note is devoted to the unique capacity of DAMPs not only to activate proinflammatory cells but also to modulate innate immune cells by changing their phenotype from inflammation-promoting to inflammation-resolving traits. Finally, growing evidence from modern evolutionary research is touched suggesting that all living creatures and organisms on our planet use the DAMPs to induce defense responses needed for their daily “struggle for life”: from plants over invertebrates up to vertebrates including mammals and humans, “DAMPs across the tree of life.”