312 IMMUNOLOGY 



(c) The appearance of antibodies for horse serum proteins 

 in the blood of many patients receiving serum injections and an 

 apparent correlation of their appearance with the development of 

 symptoms. 



(d) The shortening of the incubation period following subse- 

 quent injections of horse serum. 



While the evidence supporting the theory of von Pirquet and 

 Schick is very suggestive, it can only be regarded as circumstantial 

 in nature. One should not lose sight of the fact that horse serum 

 is foreign to man and that it, and perhaps to a lesser extent the 

 fractions obtained from it, may possess pharmacological properties 

 distinct from tlie antigenic ones. The toxic properties of antigenic 

 substances are indicated by reactions of smooth muscle to toxic 

 doses of horse serum and other antigens described by Dale (1913) 

 and Sherwood and Stoland (1923) as distinct from antigenic prop- 

 erties. The Brodie reaction (1900) in cats is usually ascribed to 

 the presence of acetyl choline in normal serum. Incidentally, it 

 has been shown in this laboratory that the Brodie reaction re- 

 sembles the anaphylactic response in cats as determined by blood 

 pressure changes (Kabler and Sherwood, 1938). These examples 

 are given to emphasize the point that serum may have toxic as 

 well as antigenic properties. Another example which may bear 

 more directly upon serum disease is the pulmonary permeability 

 and vagus irritability changes produced in dogs by the injection 

 of horse serum. Manwaring, Chilcote and Hosepian (1923) who 

 tirst described the change in pulmonary permeability that follows 

 the injection of horse serum attributed it to anaphylactic sensitiza- 

 tion. That the phenomenon is not an antigen-antibody reaction is 

 indicated by the work of Sherwood and Stoland (1930) and Sto- 

 land, Sherwood and Woodbury (1931). 



The evidence they presented may be summarized as follows : 



(a) The phenomenon is observed in animals that show no other 

 evidence of sensitization to horse serum. 



(b) It can be demonstrated by perfusion with Locke's solution 

 from which antigen is omitted. 



(c) It can be demonstrated in desensitized dogs. 



(d) The incubation period is shorter than in anaphylaxis. 



(e) The chronaxic studies indicate that following the injection 

 of horse serum there develops an increa.se in irritability of the 



