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Allogeneic blood transfusions expose a patient to many soluble and cell-bound antigens, expressed on viable and decaying cells. In particular, contaminant leukocytes are presumed to play an important role interacting with the recipient's immune system. This immune response to transfusions is influenced by the condition of the patient, and a patient in steady state will respond differently to a patient in hemorrhagic shock, under anesthesia or after surgical tissue injury. Blood transfusions affect both the innate immediate defense immune system and the adaptive immune response, the latter often resulting in antibodies and (less well characterized) cellular immunity. Removal of allogeneic leukocytes by filtration of red cells and platelet products significantly reduces febrile non-hemolytic transfusion reactions and the formation of leukocyte antibodies, causing refractoriness to platelet transfusions. However, an effect of leukocyte-containing transfusions on cellular immune functions relevant to transplant tolerance, cancer surveillance, viral replication or susceptibility to nosocomial infections is less obvious. Randomized studies showed a significant effect of removal of allogeneic leukocytes in blood transfused to cardiac surgery patients, reducing postoperative mortality. As for the other reported clinical effects of (passenger) leukocytes in blood transfusions, there is not yet sufficient evidence.