The danger model: questioning an unconvincing theory.

Janeway's pattern recognition theory holds that the immune system detects infection through a limited number of the so-called pattern recognition receptors (PRRs). These receptors bind specific chemical compounds expressed by entire groups of related pathogens, but not by host cells (pathogen-associated molecular patterns (PAMPs). In contrast, Matzinger's danger hypothesis postulates that products released from stressed or damaged cells have a more important role in the activation of immune system than the recognition of nonself. These products, named by analogy to PAMPs as danger-associated molecular patterns (DAMPs), are proposed to act through the same receptors (PRRs) as PAMPs and, consequently, to stimulate largely similar responses. Herein, I review direct and indirect evidence that contradict the widely accepted danger theory, and suggest that it may be false.