Following the intravenous injection of an overwhelming dose of pneumococci in normal animals there is a rapidly increasing bacteriemia which reaches its maximum with the death of the animal.
Immunized animals, whether the immunity is active or passive,whether the animals have their leucocytes, or whether these have been destroyed by benzol, react differently. They have incommon the ability to cause the organisms to decrease rapidly in number,and, as far as could be determined by the methods used, to disappear absolutely in a very short time from the circulation. This may be called the immediate reaction.
In actively and passively immunized normal rabbits the disappearance of the organisms from the blood is followed by their destruction in the body and the ultimate recovery of the animal. This same result occurs also in actively immunized rabbits deprived of their polymorphonuclear leucocytes by benzol. On the contrary, in passively immunized rabbits, deprived of their leucocytes in the same way, the immediate disappearance of the organisms from the circulation is followed, after a lapse of from six to twenty-four hours, by a recurrent, gradually increasing bacteriemia and the death of the animal.
It is evident that the immediate reaction is no index of the ultimate result.
This finding, that the result of the intravenous injection of an overwhelming dose of pneumococci in immunized animals may be divided into two stages, immediate and ultimate, has been utilized in the interpretation of the experiments that have been reported above.
1. Normal Rabbits.—In the normal rabbit the injection of a lethal dose of pneumococci is followed by the same immediate and ultimate response. The animal develops a rapidly progressing bacteriemia and dies.
2. Passively Immunised Normal Rabbits.—A diametrically opposed finding is obtained when the animals are passively immunized. Then following the intravenous injection of pneumococci the organisms rapidly disappear from the circulating blood and the animal recovers. The only apparent difference between these two groups of experiments is the introduction of a relatively small quantity of immune serum. Tentatively, therefore, it may be concluded that the immune serum is responsible both for the immediate and ultimate reaction in this case.
3. Passively Immunized Aplastic Rabbits.—A normal rabbit that has been previously benzolized, and in this way deprived of its myeloid elements, can not be successfully immunized. Here the immune serum injected even in excessive quantities is followed by the immediate reaction, but the ultimate result is entirely different, —the animal dies.
It may be concluded, therefore, that the serum is the potent factor in bringing about the immediate disappearance of the organisms from the circulation.
Furthermore, it is evident that the white blood cells of the myeloid tissue are necessary in order that passively immunized animals may recover following the introduction of a lethal dose of pneumococci. So far it seems that two elements are essential in the immunity process; i. e., immune bodies and white blood cells.
Corroborative evidence of the importance of the white blood cell in this reaction is offered by the hyperleucocytosis which follows the injection of antigen in actively immunized animals (Gay). This hyperleucocytosis occurs in actively immunized rabbits injected with pneumococci, after the organisms have disappeared from the circulation. It occurs at about the same time that the septicemia recurs in passively immunized aplastic rabbits.
4. Actively Immunized Aplastic Rabbits.—The experiments with actively immunized aplastic rabbits complicate the conception of the part of the white blood cells in the immunity process. When actively immunized, benzolized animals are injected with a lethal dose of pneumococci, the immediate reaction occurs just as in the passively immunized aplastic animal. Available antibodies are present and cause the disappearance of the organisms from the circulation. The ultimate reaction differs from that in the passively immunized aplastic animal. The latter develops a recurrent bacteriemia and dies. The actively immunized aplastic animal recovers.
It would seem that the white blood cell is no longer necessary in an animal that has been actively immunized, but that it must be present for the passive protection of the animal.
The ultimate reaction in immunized rabbits seems to be dependent upon some action of the white blood cells. In the passively immunized animal this may occur at the time of, or following, the immediate reaction; and if it can not occur, owing to the absence of the white blood cells, the animal subsequently dies. In the actively immunized aplastic rabbit this action has apparently occurred at a previous time and is sufficiently developed to protect the animal even though the leucocytes have been destroyed.
It may be assumed that the function of the white blood cell is exercised not directly, but perhaps indirectly, by some influence exerted on other body cells. This interrelation or interaction between the white blood cells and other cells in the body constitutes a third factor essential to the ultimate protection of the animal.
Additional evidence of this action of the white blood cell is furnished by further experiments with actively immunized aplastic rabbits. Several immunized rabbits were benzolized and then injected with a lethal dose of pneumococci. The results were the same as those indicated above. The organisms disappeared rapidly from the circulation and the animals recovered.
An interval of five days was allowed to elapse and the animals were injected again with the same amount of pneumococci. This time the reaction was different. The organisms disappeared rapidly from the circulation, but there was a recurrent bacteriemia and the animals died. In these animals the favorable ultimate result after the first inoculation of a lethal dose of pneumococci probably depended upon the presence of the immune bodies and the third factor mentioned above. After the subsequent inoculation of pneumococci the immediate reaction was followed by the recurrence of the bacteriemia and the death of the animals. It may, therefore, be inferred that the third factor present at the time of the first injection had been destroyed, and, owing to the absence of white blood cells at the time of the subsequent inoculation, it was not formed again.
It may be concluded that there are at least three elements necessary in the immunization process: (l) immune bodies, (2) white blood cells, and (3)a third factor which is dependent for its existence upon the presence of white blood cells at the time of inoculation of the pneumococci. Furthermore, this third factor may be removed if the animal is inoculated at a time when it is aplastic.