310 INFECTION AND RESISTANCE 



idea has recently found experimental elaboration in the work of Gay and Claypole, 

 who found that the reinjection of immune animals with the homologous bacteria 

 produced a specific hyperleucocytosis, that is, typhoid immune animals receiving 

 typhoid bacilli would respond with counts ranging up to 150,000 leucocytes per 

 cu. mm., whereas the normal animals rarely showed more than 40,000 to 50,000. 



This observation would tend to indicate a great advantage of the specific over 

 the non-specific methods of treatment. 



Unfortunately the results of Gay and Claypole w have not found confirmation. 

 McWilliams 55 in similar experiments found no differences in the degree of leuco- 

 cytosis between normal and immune animals in response to the injection of bacteria 

 and reported that the same degree of response followed in typhoid immune animals 

 when injected with Bacillus coli as when typhoid bacilli were administered. In 

 part, this is also stated to be the experience of Jobling and Petersen. 



The question is such an important one that the writer, with Dr. Tsen, 56 re- 

 investigated it in connection with work on the therapeutic effect of leucocytic ex- 

 tract. Our conclusions showed little agreement with those of Gay and Claypole. 



We found that when homologous Gram-negative bacilli are injected into im- 

 munized animals there seems to be a definitely higher leucocytosis in the immu- 

 nized animals than in normal controls similarly treated. The contrasts in our 

 experiments, however, were nothing like as striking as those reported by Gay and 

 Claypole. Indeed the contrast in general is so slight and so irregular that in the 

 case of the Gram-negative bacilli we were at first inclined to agree with McWil- 

 liams. There was, however, a sufficiently definite difference in an average of many 

 counts to convince us that this was more than coincidence. 



In the case of the Gram-positive cocci there was a more marked difference, in 

 that the immunized animals reacted more promptly and very much more ener- 

 getically than did the normal animals. 



It seems reasonably clear, then, that an animal reacts more energetically as 

 far as its mobilization of leucocytes is concerned when reinjected than does a 

 normal animal treated with the same variety and quantity of bacteria. 



The reaction is dependent upon a number of factors, chief among which are: 

 (1) the condition of the animal (loss of weight, etc.) ; (2) the amount of bacteria 

 injected, and (3) the interval between injections. These factors all very naturally 

 signify the necessity of avoiding too profound an intoxication of the animal. 



When immune animals are treated with heterologous bacteria that is, when 

 prodigiosus bacilli or colon bacilli are injected into typhoid immune animals and 

 vice versa there seems to be no specific difference in response. That is, the in- 

 jection of colon bacilli into typhoid animals has shown no marked difference in 

 leucocytic response from that observed when typhoid bacilli were injected into a 

 typhoid animal. In this our figures correspond with those of McWilliams. They 

 are also in keeping with the clinical experience of Kraus, Ichikawa, and others 

 which have been mentioned above. 



The injection of leucocytic extract does not arouse as vigorous a leucocytic 

 response as does the injection of bacillary protein. 



In reading these facts superficially they at first seem to be contradictory in 

 significance, inasmuch as specificity seems to exist in the fact that typhoid 

 immune rabbits or streptococcus immune rabbits respond somewhat more vigor- 

 ously than do normal controls injected with the same substance. 



However, we think that these relations are explained by the fact that animals 

 that have reacted to such organisms as the typhoid bacillus, etc., develop a certain 

 amount of non-specific tolerance against the proteose-like substances which are 

 probably responsible for a not unimportant part of the symptoms caused by the 

 bacteria. Such tolerance has been shown in the experiments made by the writer 

 with Dwyer. 



To summarize, therefore, we do not think that at present a specific leucocytosis 

 in the sense of Gay and Claypole has been demonstrated, but believe that an ani- 

 mal, immune to one microorganism, will have a slight non-specific increase of 

 resistance to other organisms. 



This does not mean that the immunity is non-specific. The destruction of 

 living bacteria is still a purely specific process, and this, of course, would 

 determine the occurrence of outcome of an infection. 



54 Gay and Claypole. Arch, of Int. Med., V, XIV, 1914, p. 662. 



55 Me Williams. Journal of Immunology, Vol. I, No. 2, 1916, p. 159. 



56 Zinsser and Tsen. Journal of Immunology, Vol. II, No. 3, 1917, p. 247. 



