EXPERIMENTAL FIGURE 23-8 The existence of antibody in serum from infected animals was demonstrated by von Behring and Kitasato. Exposure of animals to a sublethal dose of diphtheria toxin (or the bacteria that produce it) elicits in their serum a substance that protects against a subsequent challenge with a lethal dose of the toxin (or the bacteria that produce it). The protective effect of this serum substance can be transferred from an animal that has been exposed to the pathogen to a naive (unexposed) animal. When the serum recipient is subsequently exposed to a lethal dose of the bacteria, the animal survives. This effect is specific for the pathogen used to elicit the response. Serum thus contains a transferable substance (antibody) that protects against the harmful effects of a virulent pathogen. Serum harvested from these animals, said to be immune, displays bactericidal activity in vitro. Heating of immune serum destroys its bactericidal activity. Addition of fresh unheated serum from a naive animal restores the bactericidal activity of heated immune serum. Serum thus contains another substance that complements the activity of antibodies.