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SUMMARYExposure to acute versus chronic stressors and threats activates the immune system in adaptive and maladaptive manners respectively. Chronic activation arising from persistent stress exposure can contribute to an inflammatory response in the periphery and in the brain that has been implicated in stress-related psychopathology, including depression and anxiety. We review the immunology of acute and chronic stress exposure, integrate this discussion with the emerging literature linking heightened immune activation and inflammation to mood and anxiety disorders, and consider the translational implications of the immune system's role in these psychiatric conditions, with a brief overview of potential interventions.