Taste. Sight. Touch. Smell. Hearing. That M. Night Shyamalan movie. While the list has now grown far beyond those, we still associate senses with nervous systems, and by extension animals. Yet, any immune response, in any organism, must begin with the recognition of a threat, and properly calibrated immune ‘senses’ are critical to the avoidance of autoimmunity. This sense of self and non-self was originally thought to be encoded in the selection of adaptive cells. However, Charles Janeway in 1989 and Polly Matzinger in 1994 moved the field forward by introducing the notion of the innate sensing of molecular patterns characteristic of pathogens and cellular damage, respectively, as critical immune gatekeepers.

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