Short-term memory of danger signals and environmental stimuli in immune cells.

Standard definitions of immunological memory are all built on the idea that once infected, animals are protected more efficiently against a second infection. This common view overlooks an unavoidable consequence of the exposure of cells to pathogens, danger signals and environmental agents in general: stimuli change cell properties and activity in a transient yet sustained manner that extends beyond the exposure time and modulates the response of cells of both the innate and adaptive immune systems to secondary stimulation. We suggest that this transient phenomenon represents 'short-term memory' of environmental exposure and discuss the evidence that this is mediated by the persistence of long-lived regulatory molecules, notably a subset of newly deposited chromatin modifications and inducible noncoding RNAs.