220 WARFIELD T. LONGCOPE AND GEORGE M. MACKENZIE 



are more frequent when serum containing several protein constituents is 

 employed, and it has been suggested that separate attacks are caused by 

 distinct and individual reactions towards the different protein constituents 

 of .the serum. To uphold this view, Dale has shown that the time interval 

 between the injection of serum globulin and serum albumin in animals 

 and the development of sensitiveness of the cornu of the uterus of the 

 sensitized guinea-pig towards the application of the serum globulin and 

 serum albumin differs by an interval of several days. 



Recovery is complete, and there are no complications or sequelae save 

 an altered state of the tissues or hypersensitiveness towards the protein 

 employed which may persist for years. 



The development of this state of hypersensitiveness, results, as was 

 shown by von Pirquet and Schick, in a condition of the tissues that ex- 

 plains the immediate and the accelerated reactions following the second 

 dose of heterologous serum from the same animal. Two forms of the im- 

 mediate reaction were observed. First, the local, when, within fifteen 

 minutes to an hour after the subcutaneous injection of the specific serum, 

 edema, erythema or urticaria appears at the site of the inoculation, and 

 second, the general immediate reaction which is characterized by a more 

 or less severe type of serum sickness coming on within 12-24 hours after 

 the injection of serum. 



In the accelerated reaction more or less characteristic serum sickness 

 follows the injection of serum. The incubation period is shorter than that 

 observed after the first injection of serum and lasts but 3-5 days. The 

 frequency with which these secondary types of serum sickness are likely 

 to follow the second injection of serum varies. This is dependent some- 

 what upon the time interval between the first and second injections for 

 both the accelerated and immediate reactions are more likely to appear 

 when the second injection is made within 1-2 years after the first than 

 when several years have elapsed. There seems, however, to be some 

 variation amongst individuals, and the increased susceptibility undoubt- 

 edly persists longer in some individuals than it does in others, so that, oc- 

 casionally, within a period of 5 or even 8 years, a second injection of 

 specific heterologous serum may call forth either an immediate or an ac- 

 celerated reaction. 



Undoubtedly, profound though temporary changes take place in the 

 tissues of the body during serum disease. Von Pirquet and Schick showed 

 that in children even though a subcutaneous edema was not noticeable 

 there occurred during the serum sickness a relative increase in the weight 

 of the body which was considered as an evidence of the retention of fluids 

 during this period. A more exact analysis of the water and salt exchange 

 in cases of serum disease made by Rackemann, Longcope and Peters 

 showed that, during the period of serum disease, there is a marked but 

 transient retention of chlorids and water, associated sometimes with a 



