476 IMMUNOLOGY 



specific antigen. Manwaring (1910) and Scott (1910-11) report 

 that dogs and rabbits respectively become sensitive immediately. 

 In the case of guinea pigs, it is well established that at least four 

 to six hours must intervene before hypersensitiveness can be 

 demonstrated.* It is customary to test animals twenty-four to 

 forty-eight hours after they receive immune serum. 



Desensitization. — An animal can be desensitized usually by one 

 injection of an amount of antigen that either produces mild 

 shock or produces no symptoms. Large amounts can be employed 

 where the antigen is administered subcutaneously and in frac- 

 tional doses. The phenomenon of desensitization is important in 

 the study of anaphylaxis in the experimental animal or when 

 the ''Dale" reaction is being employed. It should be remembered 

 that practically all native proteins such as egg white, blood serum, 

 etc., are more or less toxic for laboratory animals. This is true 

 also for tlie iiterine liorns of virgin guinea pigs used in the Dale 

 technique. An animal or the excised uterine hoi'us ])ecome de- 

 sensitized following an anaphylactic response. While the systemic 

 symptoms of toxic reactions and anaphylactic shock can be dif- 

 ferentiated as a rule, the uterine horn response to toxic doses of 

 protein is identical in appearance with the anaphylactic response. 

 To prove that the response of a uterine horn is anaphylactic 

 rather than toxic, it is customary to repeat the shock dose. This 

 should produce no reaction if desensitization has occurred. If 

 a reaction occurs, it suggests that the original response might 

 have been toxic rather than anaphylactic. The failure to observe 

 such a criterion, described by Dale, has led to much confusion 

 in the literature. Silva (1941) has suggested that trypsin may 

 play an indirect role in anaphylaxis. 



The Refractory State. — Animals supposedly rendered sensitive 

 may not develop symptoms following the injection of a shock 

 dose of antigen for several reasons which may be enumerated as 

 follows : 



1. They may not have been made sensitive either by the injec- 

 tion of antigen or by passive transfer. Antigens vary in their 

 sensitizing capacity, and animals vary in their capacity to re- 

 spond and become sensitive. Crystalline egg albumen is superior 

 to native egg white as an antigen. 



♦Bronfenbrenner maintains that immediate sensitization occurs if liomologous 

 rather than heterologous immune serum is used. 



