Model of antibody-initiated complement activation in ischemia reperfusion injury and hypothermia effects on complement activation. Hypoxic insult induces expression of 'neoantigens' on the surface of vascular endothelial cells. These neoantigens are recognized by natural antibodies (IgM) initiating complement activation leading to downstream inflammatory effectors. Therapeutic hypothermia temperatures were shown to increase C1/C1q binding, increase opsonization with C4-fragments and C3-fragments, increase C5a anaphylatoxin generation, and increase eukaryotic cell lysis via membrane attack complex (MAC) formation. Increases in complement function demonstrated in this study are shown in grey. PIC1 inhibits complement activation at C1 preventing C4 activation.