J Exp Med. 1916 Jul 01;24(1):7-24. doi: 10.1084/jem.24.1.7.
The Journal of experimental medicine
C G Bull
PMID: 19868030 PMCID: PMC2125412 DOI: 10.1084/jem.24.1.7
Intravenous inoculations of from 1 to 3 cc. per kilo of body weight of a bouillon culture of virulent pneumococci produce septicemia and meningitis in dogs. The injected pneumococci leave the circulation rapidly, but begin to reinvade the blood from 24 to 48 hours later. The septicemia reaches its climax between the 4th and 5th days and then abruptly declines, the blood becoming sterile within from 1 to 3 days after the height of the septicemia is reached. The initial disappearance of the pneumococci from the circulation has been found to be due to agglutination of the diplococci in the blood stream and accumulation of the clumps in the lungs, liver, spleen, etc. If the dogs are reinoculated during the ascension of the septicemia, the injected diplococci leave the circulation as rapidly as in normal dogs. Cultures isolated in this stage of the infection, both before and from 3 to 4 hours after the reinoculation, are resistant to the agglutinins and opsonins of immune sera that agglutinate and opsonize the cultures with which the dogs were originally infected. Thus it follows that the pneumococci are able to reinvade the circulation because they have acquired a fastness to the existing antibodies and not because the antibodies have been bound or exhausted. By reinoculating dogs at the time of the crisis in the septicemia it has been shown that the agglutination of the pneumococci is more rapid and complete and that the diplococci leave the circulation much more rapidly than in normal dogs. Hence acquired antibodies are operative within the animals at this time although they cannot be demonstrated in vitro until from 24 to 48 hours later. Pneumococci isolated as the infection is subsiding are more susceptible to the action of immune sera than the original cultures injected. It is probable that all the dogs would have survived the infection if a meningitis had not developed. In the acutely fatal cases of meningitis few pneumococci are phagocyted, while in the milder and convalescent cases much phagocytosis occurs. It is suggested that the incubation period of infectious diseases is due to the fact that the infecting agents must become adapted to the adverse conditions encountered in the newly infected host before they can multiply sufficiently to produce the symptoms of disease. It is further suggested that epidemics may arise because the infectious agent is passed from person to person in the ascending stage of the disease and thus enters new hosts in a state of maximum resistance to the natural antibodies of such individuals. When early contacts are avoided, epidemics tend to subside because the infectious agent is weakened by the action of acquired antibodies during the period of convalescence.
