Components of donor cells are incorporated into EVs (exosomes, sMVs) that contain diverse cargoes, such as signaling proteins, transcriptional regulators, various RNA species, DNA, and lipids. Multiple machineries are thought to be involved in exosome biogenesis of ILVs and MVBs. ESCRT components are involved in an ESCRT-dependent intracellular pathway that traffics MVBs and their ILV contents (exosomes) out of the cell, while other ESCRT-independent pathways (lipid dependent) have also been described. Members of the Rab GTPase family have been shown to modulate exosome secretion and are thought to act on different MVBs along ESCRT-dependent and -independent endocytic pathways. It is not known whether each of these pathways acts on different MVBs or on the same MVB concomitantly or how exosome/ILV-loaded MVBs differ from those destined for lysosomes. Even less is known about the molecular machinery regulating outward budding of the plasma membrane and sMV release, apart from a requirement of ARF6, acid sphingomyelinase activity, and some ESCRT components (ESCRT-I). EVs may interact with recipient cells by direct signaling through ligand/receptor molecules on their respective surfaces or by their uptake via direct fusion of EV and recipient cell plasma membrane (110, 111) through lipid raft-, clathrin-, and calveolae-dependent endocytosis, macropinocytosis, and phagocytosis (112–117). EVs can be involved in antigen presentation and in the transfer of both MHC molecules and antigens, thereby participating in immune regulation (118–120). APC, antigen-presenting cell.