170 A MANUAL OF BACTERIOLOGY 



appear between the eighteenth hour and the fifth day after 

 the second injection of serum. 



The immediate and accelerated reactions may occur a 

 long time after the first course of serum treatment if more 

 serum be given. Goodall records one case in which over 

 four years elapsed between serum treatments for first 

 and second attacks of diphtheria, an accelerated reaction 

 occurring after the reinoculation for the second attack. 



The amount of serum given does not definitely influence 

 the result. The remarkable features of the phenomenon 

 are (1) they do not occur unless an interval of about 

 twelve days or more elapses between the two injections 

 of serum ; (2) the long period which may intervene between 

 the two injections of serum and still be accompanied by 

 symptoms ; (3) the serious nature of the condition in 

 some instances. 



The explanation of the phenomenon is difficult. Un- 

 doubtedly the symptoms are due to some substance in 

 the serum which has a toxic action, and have nothing 

 to do with the antitoxic constituent, for normal serum 

 produces the same effects. 



In experimental anaphylaxis produced in animals by 

 the injection of normal serum, it is found that the con- 

 dition only occurs if the two doses of serum are separated 

 by an interval of about twelve days or more ; the first is 

 termed the sensitising, the second the reacting, dose. The 

 larger the sensitising dose, the longer must the interval 

 be for the reacting dose to produce a maximum effect. 

 Moreover, the two injections must be of the same serum 

 or other protein ; thus a first injection of horse serum 

 followed by a second injection of rabbit serum would 

 not produce it. Extremely small doses of serum will 

 also bring it about ; and lastly, ansesthetisation, when 

 the second dose of serum is given, prevents the develop- 

 ment of the symptoms a very extraordinary result. 



