Integrating innate and adaptive immunity in the whole animal

The mammalian defense system can respond to a variety of threats, but this capability is not just a simple alarm system for triggering antigen-present ing cells and initiating cellular immunity. Instead, the body is an integra ted system in which nearly every cell type can relay the alarm through the production of chemokines, which recruit specific inflammatory cells to the target tissues. This chemokine production is carefully regulated at several levers so that the kinetics and character of local tissue inflammation is tailored to the specific threat. First, the production of nuclear facror-ka ppa B-regulated chemokines can be modulated in non-bone marrow-derived cell s through transcriptional repression mediated by RelB. RelB is also implica ted in the differentiation of lymphoid dendritic cells, suggesting that thi s gene regulates the transition from acute inflammation to adaptive immunit y Second, tissue parenchymal cells, in their capacity as sentinel cells, ar e able to produce different patterns of chemokines in response to different alarm stimuli. Third, cells from different tissues also show distinct pote ntials for chemokine responses so that the non-specific damage from inflamm ation might be avoided in some cases. Finally, the differentiation of T-cel l effecters allows for further regulation of local inflammation as their cy tokines can also affect chemokine production. This integration of innate an d adaptive immunity allows for both rapid responses and dynamic regulation of inflammation in vivo.