Topology, dynamics, and heterogeneity in immune signaling

Development and function of the immune system depends on cells exchanging information between themselves and with their environment. This information is processed and integrated by complex signal transduction and gene regulatory networks with rich temporal dynamics. A growing body of evidence points to a combination of network topology and temporal dynamics as a fundamental link between stimulus and function. Recent findings also bring cellular variability and stochastic events to the forefront as additional determinants of cell population responses to immune cues. In this article, we review examples of how the trinity of network topology, temporal dynamics, and cellular variability together determine the immune function. In particular we focus on Nuclear Factor kappa-B and T-cell receptor signaling networks as they have proven fertile ground for studying how function arises from the combination of topology, dynamics, and variability in a context of great clinical importance.