Dissecting immune responses by next generation sequencing methods at single cell resolution provides novel insights into cell states, including antigen receptor diversity, cell-cell interactions in tissues, and how cellular phenotypes change in the context of adaptation from lymphoid to non-lymphoid tissues. We elucidate in detail development of immunity and how the immune system contributes to tissue homeostasis, as well as gaining a deepr understanding of immunity to infection in the mucosa and blood. The immune compartment is fast-evolving across species and highly variable in humans, and single cell genomics allows us to understand the phenotypic impact of this variability at single cell resolution.