AIHA can be caused by a number of different classes of antibody, with IgG and IgM antibodies being the main causative classes. Depending on which is involved, the pathology will differ. IgG is not very effective at activating complement and effectively binds the Fc receptor (FcR) of phagocytic cells, AIHA involving IgG is generally characterized by phagocytosis of RBCs. IgM is a potent activator of the classical complement pathway, thus, AIHA involving IgM is characterized by complement mediated lysis of RBCs. IgM also leads to phagocytosis of RBCs however, because phagocytic cells have receptors for the bound complement (rather than FcRs as in IgG AIHA). In general, IgG AIHA takes place in the spleen, whereas IgM AIHA takes place in Kupffer cells – phagocytic cells of the liver. Phagocytic AIHA is termed extravascular, whereas complement-mediated lysis of RBCs is termed intravascular AIHA. In order for intravascular AIHA to be recognizable, it requires overwhelming complement activation, therefore most AIHA is extravascular – be it IgG- or IgM-mediated.