April 24, 1908] 



SCIENCE 



647 



is said to be immune. By carefully regu- 

 lating the size of the second dose one can 

 develop in both the egg-white and the 

 typhoid animals the first and second stage 

 of the symptoms of proteid poisoning with- 

 out reaching the convulsive stage. 



The effect of the poison depends not only 

 upon the amount set free, but also upon 

 the rapidity with which it is liberated. 

 The poison kills by its action on the respi- 

 ratory center. This is demonstrated (1) 

 by the continued beating of the heart for 

 some minutes after respiration has ceased, 

 (2) by the symptoms which are those of 

 asphyxiation, and (3) by the post-mortem 

 findings, such as a fluid state of the blood 

 and the engorgement of certain internal 

 organs with' ecchymoses, as found by Gay 

 and Southardt. I infer that the poison 

 does not destroy the cells of the respiratory 

 center, but puts them out of commission 

 or interrupts their normal function. The 

 basis for this inference is the ready and 

 apparently complete recovery of animals 

 after manifesting the first and second 

 stages of poisoning. Recoveiy after the 

 development of the convulsive stage occurs 

 but rarely. My reason for concluding that 

 lytic immunity consists in the development 

 of a proteolytic ferment is founded upon 

 what seems to me a demonstrated fact that 

 the symptoms are due to a cleavage of the 

 proteid molecule into a haptophore and a 

 toxophore group, and we know of no agents 

 in the animal body save enzymes that are 

 capable of splitting up proteids. I am in- 

 clined to the opinion, subject, of course, to 

 change with additional knowledge, that the 

 cells that become sensitized and in which 

 the zymogen is stored are connective tissue 

 cells and that in order to be sensitized they 

 must come into direct contact with the 

 haptophore group of the proteid, and the 

 presence of the same group is necessary to 

 convert the zymogen into an active enzyme. 

 I think it most probable that the sensitiza- 



tion of a cell consists in causing a rear- 

 rangement in the molecular structure of 

 some one of its proteid constituents. Sen- 

 sitization may be local or general; it can 

 exist only in those tissues that have come 

 under the direct influence of the hapto- 

 phore. This explains why the soluble hap- 

 tophore split off from the bacterial cell is 

 more efficient both in 'sensitizing and in 

 activating the body cell than is the un- 

 broken bacterial cell. Typhoid bacteria 

 introduced into the abdominal cavity of an 

 unsensitized animal may be acted upon by 

 phagocytes, but no lytic action takes place 

 until the body cells have been sensitized by 

 the bacterial proteid ; and their sensitization 

 is at first local. When a coagulated proteid 

 is injected into the peritoneal cavity of a 

 sensitized animal the lytic action is local 

 and the phenomenon of hypersusceptibility 

 is never manifested, except when the activ- 

 ating dose is introduced into the animal in 

 soluble form ; then a large number of cells 

 are activated at once, the proteid is split up 

 with explosive rapidity and the poison, 

 being set free in the circulating blood, 

 reaches the respiratory center promptly 

 and death as a rule follows speedily. The 

 striking experiments of Pirquet with vac- 

 cination are, according to my interpreta- 

 tion of them, beautiful examples of local 

 sensitization and consequently of local re- 

 action. The same is, I think, true of the 

 Calmette eye reaction with tuberculin. In 

 some tubercular individuals the tissue of 

 the conjunctiva has become sensitized by 

 the split products resulting from the break- 

 ing up of the tubercle bacilli and the first 

 application causes a reaction. But the 

 same thing is shown more strikingly when 

 the eye of a non-tubercular individual is 

 sensitized by a first application and then 

 activated by a second when the reaction 

 is prompt, sometimes quite violent, and 

 confined sharply to the parts touched by 

 the first application. - 



