Abstract: The present invention relates to the modulation of Natural Killer (NK) cells in vitro or in vivo through the use of activating or inhibiting ligands of CD27, such as antibodies, for a regulation of the immune response against several different diseases, such as viral infections, cancer, bacterial infections, sepsis as well as immunological diseases. In a preferred embodiment, the inventors were able to improve the host resistance against Influenza virus and cancer through the application of anti-CD27 antibodies. In a different setting the inventors were able to prevent the onset of a lethal bacterial sepsis by preventing the activation of NK cells via CD27. The invention furthermore relates to screening assays for ligands of the surface marker CD27.