Generalised Bacterial Infections. 25 



disease progresses while the defensive mechanism makes no 

 answering effort. There is no considerable rise in the opsonic 

 index of the blood for the first five days of the disease (Fig. 2). 

 This phenomenon was observed in nine rabbits, none gave a con- 

 trary result. Three of the rabbits died at the end of this critical 

 period. In those which survived, the opsonic index usually rose 

 rapidly, and recovery set in. In guinea-pigs a similar period of 

 inertia was observed, most of the animals died about the fifth 

 day, a few lived longer and shewed a rise in the opsonic index, but 

 only one recovered. 



Fig. 1 gives the opsonic histories of a batch of ten guinea- 

 pigs, which were all infected with similar doses on the same day, 

 and which have been arranged in three groups according to the 

 length of time during which they survived an infection. It is 

 seen that the three guinea-pigs which lived longest had shewn 

 high indices previous to their infection, and also shewed a capa- 

 bility to produce a relatively large increase in opsonine in response 

 to the disease. The animals which died earlier were those with a 

 past history of medium or low indices. Their indices remained 

 low during the disease. 



From the above it is clear that the natural reaction to the disease 

 is delayed so late, that many rabbits and most guinea-pigs may be 

 said to die without a struggle. An injection of killed bacilli 

 beneath the skin of a normal rabbit is followed by a very different 

 sequence of events (Fig. 2). In this case the animal responds to 

 the stimulus with a prompt increase of opsonine, which reaches 

 about double the initial value within 48 hours. The same result 

 was obtained with five rabbits which were given various doses 

 between 5000 million and 80,000 million killed bacilli per kilo- 

 gramme of body weight. A smaller dose evoked a doubtful 

 response or none at all. A similar contrast between the diseased 

 and inoculated rabbits, also appeared with regard to the formation 

 of agglutinin (Fig. 3). Five rabbits which were inoculated with 

 killed bacilli, all had strongly agglutinating sera on the fifth day. 

 Three diseased rabbits, which were tested, produced agglutinating 

 sera first on the ninth day, and even then the observed agglutinating 

 power was relatively small. 



It cannot be held that, in disease, the protective mechanism 

 is held in check by an inhibitory influence. If a normal rabbit 

 responds readily to a subcutaneous inoculation, a diseased rabbit 

 responds still more readily to such a stimulus, as is shewn on 

 Fig, 4. After a dose of 250 million dead bacilli per kilogramme 

 of body weight on the fourteenth day of the disease, the opsonic 

 index of rabbit 10 rose from 1*5 to 2"5 within 24 hours. In dealing 

 with diseased animals, however, the dose of vaccine must be care- 

 fully regulated. An excessive dose produces an irregular reaction 

 (Figs. 5 and 6). 



