The immune system is fighting a constant war against pathogens in its own territory. This requires a potent arsenal for efficient control of pathogens but also requires tight regulatory mechanisms in order to avoid excessive collateral damage. Maintaining equilibrium is the daily challenge of the immune system. Interactions between pathogens, antigen-presenting cells (APCs) and lymphocytes are critical in this balancing act. Of particular importance for the generation of protective immune responses is the induction of activation programs in APCs directly by pathogens or by T cell derived factors, such as CD40L, RANKL or cytokines. In order to counterbalance overshooting immune responses, T cells and APCs secrete anti-inflammatory cytokines that are key for maintaining a healthy balance between protection and immunopathology.