Mapping the dynamics of the vertebrate immune system

Cells of the immune system display a wide variety of behaviors that enable them to coordinate responses to infection. The migration behavior of immune cells has been studied in a variety of contexts, typically focusing on the dynamics of a single cell type in a local environment, either in the context of a tissue or in vitro. How does the entire immune system, comprising all immune cells and cell types, orchestrate a response at the scale of the whole organism? This question remains to be explored. We employ the vertebrate, larval zebrafish as a model system to address this question, as their immune system resembles ours, comprising both innate and adaptive immune cell types and highly conserved dynamics during early development. Further, their genetic tractability, transparency for imaging and small size makes them an ideal system to chart the dynamics of all immune cells. State of the art, custom light sheet fluorescence microscopy allows for 3D visualization and quantitative characterization of immune cell dynamics at the organismal scale at unprecedented spatiotemporal resolution. We track all immune cells in these datasets and quantify individual movement patterns using step size and rotation distributions computed from their trajectories. We measure a wide distribution of diffusion coefficients indicating differential strategies for migration that can often be context dependent. We also observe rapid morphological transitions for individual immune cells at steady state. We use these morphological and kinetic measurements to develop an atlas of observed immune cell behaviors and explore whether cells can be classified based on their behavioral fingerprint.

From such quantification and analysis, we gather information on the architecture of the immune system, the nature of information flow, the biophysical rules that may be crucial for a robust network and hence immune response at the scale of the organism.