The Behavior in Vivo of Certain Relatively Pure Antigens

The experiments are of interest in several respects. It is clear that crystallized egg albumen is rapidly eliminated from the circulation and in the experiments cited it could no longer be detected after 18 or 19 hours. A considerable portion of it rapidly passes through the kidney in an apparently unaltered state. Evidently this passage begins almost at once and may continue for a day or two. In an experiment not reported in this paper, egg albumen appeared in naturally voided urine 2 hours following its injection into the peritoneal cavity. In the experiments reported no urine was voided until 5(1/2) and 6(1/2) hours following intravenous administration, but in each instance egg albumen was present in considerable amounts. However, sufficient egg albumen must have been utilized to produce antibody. It is hardly to be expected that such a protein, whose elimination is so rapid, could persist unaltered within the body and reappear within the circulation coincident with its antibody. The behavior of the protein cannot be ascribed to alterations which may have taken place during the process of crystallization since Ascoli showed that the proteins of egg white readily pass from the circulation into the urine. Certain observations of the writer confirm this point. The experience of Alexander, Becke, and Holmes who exposed sensitized guinea pigs to sprays of dilute egg white with the result that 80 per cent of the animals developed symptoms of anaphylaxis, further strengthens the contention that certain of the membranes are readily permeable for the proteins of egg. The conditions following the injection of casein are different. There is no appreciable passage through the kidney. Casein is present within the circulation for a considerable period; it could be detected in the blood serum 12 and 13 days after its introduction into the peritoneal cavity. Antibody appeared on the 7th and 8th days, respectively, so that both antigen and antibody were present in the serum for a period of 3 or 4 days. The phenomenon of antigen and antibody occurring together might be explained on the ground that certain proteins are utilized slowly and that the antibody found in the blood, usually after the 7th day, results from the portion of antigen first utilized. During the next few days a continual supply of antibody enters the circulation and during the period there is a steady utilization of the antigenic substance; it is possible that during this time there is constant union of antigen and antibody within the blood, with the slow utilization of the antigen and a slight utilization of the antibody which is made up by a slow increase from the body cells. Thus there would be a period in which considerable antigen would be present with weak antibody, succeeded by a second period when the amount of antigen would be small with well defined antibody, and finally only antibody. Certain observations tend to support such a view. Bayne-Jones injected rabbits whose serum contained precipitin from egg albumen with this substance and noted the occurrence of both antigen and antibody for a period of 48 hours. Some of his experiments in vitro are equally suggestive. In one instance a rabbit well immunized with egg albumen was injected intravenously with this substance. An hour later it was bled and the stored serum refrigerated for a period. During this time there was a slow spontaneous precipitation with a decline in both precipitin and antigen titer, but even after 6 days both were present. After a longer period only antigen remained. P. A. Lewis and D. Loomis have shown that an injection of sheep red blood cells in guinea pigs results in a well defined hemolysin titer about the 9th day, followed by a definite decline, with a secondary rise in hemolysin until the peak is reached on the 20th day. It becomes evident, then, that the reaction of the rabbit to a single injection of a relatively pure protein will depend on the character of the protein injected. When crystallized egg albumen is administered it is rapidly eliminated from the circulation. The rapid disappearance of the egg albumen from the blood stream is partly accounted for by its prompt elimination through the urine. Antibody appears in the serum from the 7th to the 10th day. Casein behaves differently. It persists in the blood for a considerable period; after the 7th or 8th day both antigen and antibody may be demonstrated in the blood. Casein cannot be detected in the urine following its injection into the body. The behavior of casein within the body affords an analogy with the conditions frequently noted after the administration of foreign serum, in both cases both antigen and antibody may be present in the circulation together.