(A) After ischemia, circulating white cells stick to the cerebral endothelium and extravasate into the brain and meninges. Recent evidence implicates the skull bone marrow as a source of meningeal inflammatory cells (101). Cerebral ischemia also damages brain cells, which release DAMPs. DAMPs activate innate immune receptors on microglia and other cells, leading to the release of cytokines and chemokines, which, in turn, promote additional neutrophil entry. Neutrophils damage the brain by producing ROS, metalloproteases (MMPs), perforins, cytokines, and neutrophil extracellular traps (NETs). Activation of the complement cascade (Cmp) also damages brain cells. (B) Brain damage triggers a neurohumoral response (via the hypothalamic-hypophyseal axis and autonomic nervous system), which leads to activation of the adrenal glands and secretion of glucocorticoids and catecholamines. Brain-derived DAMPs leak into the circulation and activate systemic immunity, mobilizing innate immune cells form lymphoid organs and the gut. The increase in gut permeability may release bacteria and their metabolites into the circulation. (C) DAMPs activate systemic immunity through pattern recognition receptors, including TLRs and RAGE, on immune cells. This activation phase is followed by immunodepression, attributable mainly to the systemic effects of β-adrenoreceptors, which increases the propensity to post-stroke infections.