Immune responses to stroke: mechanisms, modulation, and therapeutic potential

tors on innate immune cells, enabling recognition of a wide variety of molecular complexes that are perceived as foreign and potentially damaging (dangerassociated molecular patterns [DAMPs]).Innate immune cells include neutrophils, monocytes, macrophages, and DCs, as well as selected groups of lymphocytes, e.g., NK cells, γδ T cells, and others (33).The ensuing response is directed at eliminating the potential threat through a massive and indiscriminate humoral and cellular inflammatory response.In contrast to innate immunity, adaptive immunity requires several days to develop and retains memory of antigen exposure (32).Adaptive immunity is based on highaffinity receptors, including T cell receptors and immunoglobulins.Innate and adaptive immunity are closely interrelated (32).Innate immune cells, DCs in particular, initiate adaptive immune responses via antigen presentation to lymphocytes, the typical adaptive immune cell.In turn, lymphocytes undergo clonal expansion in lymphoid organs and return to the circulation to engage the antigen throughout the body.The resulting humoral and cellular responses seek to neutralize the offending antigen with a remarkable degree of selectivity and specificity.As detailed below, cerebral ischemia engages both innate and adaptive immunity (Figures 1 and2), which play a critical role in both the acute and chronic phases of the damage. Cerebral ischemia and innate immunity: the brain viewCirculating innate immune cells are quickly engaged at the onset of arterial occlusion, ultimately resulting in invasion of the ischemic brain by blood-borne immune cells and activation of brain-resident cells, which can be either beneficial or detrimental (Figure 1).