ANAPHYLAXIS IN ITS RELATION TO DISEASE 163 



general symptoms would have occurred irrespective of any antibody 

 production. This conclusion, however, is disproved by the fact 

 that the size of the vaccine dose neither hastens nor retards the devel- 

 opment of the symptoms, and is further especially strikingly demon- 

 strated in experiments of v. Pirquet, where the same patient was 

 vaccinated on successive days. When this was done all points of 

 vaccination developed their areola on the same day, so that in a 

 given instance when the first vaccination reached its inflammatory 

 maximum after eleven days the subsequent vaccinations were equally 

 advanced after ten, eight, and four days. 



In this connection it is interesting to note that whereas the vacci- 

 nated individual has acquired a marked immunity to infection with 

 the organism of either human smallpox or cowpox, he is, never- 

 theless, hypersensitive to its proteins, v. Pirquet thus remarks 

 that by frequently vaccinating himself he brought the skin of his 

 forearm to such a state of hypersensitiveness that after twelve hours 

 a papule, measuring on an average 9 mm. in diameter, i. e., a size 

 only reached in primary vaccinations on the seventh day, develops. 

 This, of course, is closely analogous to what we see on reinjection 

 with horse serum during the first six months following the primary 

 injection, and represents what v. Pirquet terms a hastened reaction. 

 An immediate reaction is here not observed, probably because it is 

 obscured by the traumatic reaction. 



If now we apply the same principle to the study of tuberculosis 

 it will be seen that here also various phases of the disease can be 

 satisfactorily explained upon the same basis (v. Pirquet) . In experi- 

 mental tuberculosis, produced in cattle, a quiescent period of "incu- 

 bation," extending over eight days, likewise follows the inoculation, 

 provided that the initial infecting dose was sufficiently large, exactly 

 as in connection with vaccination and the development of primary 

 serum sickness (Fig. 6). Coincidently with the appearance of 

 antibodies clinical symptoms then develop; but whereas in vaccina- 

 tion the production of antibodies leads to the prompt destruction 

 of the invading organism, the tubercle bacilli, owing to their peculiar 

 waxy envelope, no doubt succeed in maintaining themselves in the 

 body of the infected organism, and may, if their initial number was 

 sufficiently large, even cause the death of the host. A certain num- 

 ber, of course, are destroyed, and, as protein antigen and antibody 

 thus coexist, a more or less continuous formation of anaphylatoxin 



