Figure 1. The Tide Model for the Control of Immune Response.
We define primary signal as a triggering signal or signals which initiate specific immune cell response to extracellular stimuli. The co-signals, which could be either costimulatory or coinhibitory, are modulator of signal one, and decide the direction and magnitude of a cellular reaction, leading to activation of naïve cells (Response), deactivation of already activated cells (De-response) or unresponsiveness (Un-response).