Fig. 1.

Impact of heterologous innate immune stimulation on activation thresholds. An immune reaction can be compared with a chemical reaction. The activation threshold is determined by the activation energy, i.e., the energy difference between the basal energy level and the energy of the transition state. a In the case of a non-adaptive response, the immune system becomes activated and returns to the former, homeostatic energy level that has been established in a calibration process (red line). Heterologous stimuli (e.g., adjuvants) may act like catalysts and lower the energy level of the transition state thereby lowering the activation threshold of the primary response (green line). b If the system is primed by an immune response, it returns to a higher basal energy level in a primary response. c This lowers the activation energy required for the secondary response (green line). d Heterologous stimulation (e.g., by adjuvants) can lower the activation threshold of the primary response and the system can be primed in addition (green line). e The result is an even lower activation energy required for the secondary response (green line)