1913] Charles Frederick Bolduan 257 



sensitive. In guinea-pigs treated with small doses of horse serum, 

 from 12 to 14 days suffice; with large doses, the time required is 

 longer, and may extend over weeks or even months. In any case, 

 in Order to produce severe Symptoms, it is important that the second 

 injection be large, say 5 to 10 c.c. in a guinea-pig. This phenom- 

 enon, spoken of as anaphylaxis, has come to occupy an important 

 place in the theory of infection and immunity. What is the ex- 

 planation of the phenomenon? 



Enteral and parenteral introdiictions of protein contrasted. We 

 know that the subcutaneous, intraperitoneal, or intravenous intro- 

 duction of alien protein is followed by the formation of antibodies ; 

 at the same time it can readily be shown that no antibodies develop 

 after the oral introduction of milk, eggs, or even of raw meat. In 

 other words there is a marked contrast in the behavior of the body 

 toward enteral and parenteral introductions of protein. In the 

 former the protein is acted on by specialized cells, which, through 

 their pepsin, trypsin and enterokinase, and erepsin, break down the 

 protein molecule so that it loses its species identity. After this, 

 absorption takes place, and with it there is a synthesis or rearrange- 

 ment of the molecule whereby it is built up into protein specific to 

 the body. Under normal conditions it is impossible to produce 

 antibodies by feeding alien protein, though precipitins have been 

 produced by overfeeding animals with large amounts of alien pro- 

 tein. When protein is introduced parenterally it gives rise to the 

 formation of specific antibodies. In the case of the sensitized ani- 

 mals described above, the first injection causes the production of 

 specific antibodies, among them specific cytolysins acting on the alien 

 protein molecule. When the second injection comes, the alien pro- 

 tein is at once laid hold of by this antibody, protein cleavage results, 

 and with it the liberation of poisonous cleavage products. These 

 cleavage products cause the severe Symptoms and even death that 

 characterize anaphylaxis in guinea-pigs. That similar Symptoms do 

 not arise in the enteral digestion of protein would then be explained 

 by saying that, in the specialized digestive apparatus, provision has 

 been made either for preventing the formation of such poisonous 

 cleavage products or for neutralizing them (conjugations?) before 

 they can cause injury. 



