Figure 2.

Two distinct criteria of innate immune recognition. Innate immune responsiveness is an integrated function of two independent criteria of immune recognition. One criterion is the well-appreciated discrimination along a self vs. other (non-self) axis. The second reflects the discrimination between viable and dead (particularly apoptotic) cells. These two distinct criteria of recognition are represented here along orthogonal axes. Whereas recognition of non-self determinants engages a signal transduction pathway linked to inflammatory outcomes, apoptotic recognition triggers distinct signaling events that result in antagonistic, anti-inflammatory outcomes. The placement of necrotic cells in this schema is less obvious. At least with regard to inflammatory responses, necrotic cells are more like pathogenic invaders than apoptotic cells, although their ability to elicit inflammatory responses tends to be modest at best (10,13).