Schematic representation depicting how a confederacy of innate immunity-based genes and cells may conspire to create a psoriatic lesion. Whether triggered by an exogenous event that disrupts KC barrier function (with or without bacterial infection) or by an endogenously-derived infiltration of activated immunocytes, the final mature psoriatic plaque includes an epidermal compartment resistant to infections, apoptosis, and transformation. The complexity of interactions between innate immunity and acquired immunity in skin is depicted as a multi-step model highlighting 2 key abnormalities in psoriasis, including (a) defective terminal differentiation/barrier function and (b) hyperreactivity of the skin immune system including T cells bearing NKRs, which can evolve into a full-fledged Th1-type cell-mediated reaction involving adaptive immune components.