No abstract

University, and the Pressb ytenhn Hospital. Cole' observed, in 1904, that after an animal has been immunized subsequent injection of the same antigen causes antibodies to appear eqrlier than after the first injection. Previously immunized animals also show circulating antibodies after the injection of amounts of homologous antigen which, in animals injected for the first time, are insufficient to cause the appearance of demonstrable antibodies. A clinical counterpart of these experiments has been observed in what is called accelerated serum disease : symptoms and circulating precipitin appear earlier when a patient is treated a second time with serum.It has been observed,* too, that individuals previously vaccinated against typhoid may show a reappearance of typhoid agglutinins during the course of typhus. Bieljng3 studied this anamnestic phenomenon in rabbits, using as antigens the Shiga and His-Russel types of 23. dysenteriae and B. typlzosus. H e found that the heterologous antigen would call back, so to speak, the agglutinins for the antigen previously administered.I n subjecting the anamnestic reaction to a systematic study we have used 4 antigens sufficiently remote from each other in biological origin to exclude group reactions, A series of 18 rabbits has been studied over a period of 3% years. The antigens used were horse serum, chicken serum, crystalline egg albumin and B. typho-SW. Immunization with horse serum and chicken serum was accomplished by giving 3 intravenous injections (0.5 cc., 1.0 cc., 1.5 cc.) a t intervals of 5 days. For the egg albumin immunization, 3 intravenous injections (1.0 cc., 2.0 cc., 3.0 cc.) of a 3 per cent solution at 5 day intervals were given. Suspensions of B. typliosus a t first heat killed, and later, living organisms were injected intravenously 7 times in the course of 16 days, the number of organisms amounting to approximately 5th billion. Titrations of precipitin or agglutinin were made 5 days after the last antigen injection, and then at intervals of 7 days. Reinjection with a second antigen was not made until the antibodies produced during the previous immunization had disappeared entirely from the circulation. I t was found that rabbits previously injected with horse serum would freat GEORGETOWN UNIV MED CTR on July 15, 2015 ebm.sagepub.com Downloaded from

In studying the rate of disappearance of horse serum and the curves for circulating precipitin in a group of serum-treated patients it was noted that individuals who have severe serum disease are good precipitin formers and that at the time the precipitin in the circulation reaches the crest of its curve or soon thereafter the precipitinogen rapidly disappears from the blood stream. On the other hand in those individuals who after a first administration of foreign serum, show very mild or no symptoms of serum disease little or no precipitin is demonstrable in the patient's serum and the precipitinogen persists in the circulation for a long period. Intermediate types were also encountered. From these results it seemed a t least plausible to assume that an important factor in determining the rate of disappearance of the foreign serum from the circulation was an intravacular union of antibody and antigen. That such an assumption is erroneous seems probable from the following experiments :In one series of experiments 12 previously immunized rabbits were injected intravenously with amounts of horse serum (3.00 C.C. or 6.00 c.c.) comparable to the amounts used therapeutically in the group of patients studied. The animals were then bled every second or every third day and the precipitin and precipitinogen in the serum titrated. Six of the animals had a high titer (1:20,000 or higher) of precipitin in the circulation a t the time of reinjection, 2 had a moderately high titer, I had only traces of precipitin, and 3 had no circulating precipitin. Two of the 3 rabbits with no circulating precipitin had been immunized 10 months previously and at that time had developed a high titer of precipitin which had entirely disappeared before the reinjection. Presumably such previously immunized rabbits which had shown