Histological and Serological Sequences in Experimental Hypersensitivity

1. Groups of normal rabbits were given, single intravenous injections of foreign proteins in doses of 1 gm. per kilo, bled at regular intervals for serologic studies, and sacrificed after varying lengths of time for pathological studies. The protein solutions used were of crystallized bovine serum albumin, bovine serum gamma globulin, and bovine serum. The experiments were planned, first, to correlate the sequence of pathological and immunological changes, and second, to compare the responses to two chemically and immunologically distinct plasma protein fractions and to the whole serum of the same species. 2. (a) The principal pathological lesions in rabbits given bovine serum were similar to those which have been previously observed following, the injection of horse serum and were characterized by widely dispersed but segmental acute inflammatory lesions of the arteries. These lesions were at their height 2 weeks after injection and showed marked repair at 4 weeks. (b) Crystallized bovine serum albumin produced lesions almost exclusively confined to the arteries which were at their height at 2 weeks, were healing at 3, and healed by 4 weeks. The lesions were less numerous and less intense than in animals given whole serum and were only found in some of the animals. (c) Bovine serum gamma globulin elicited quite different histologic sequences. The most striking lesions involved the glomeruli of the kidneys, and to a lesser degree, the heart. Lesions in the liver and joints were present but less conspicuous, and arterial lesions were rare and slight in degree. The lesions not only differed from those in rabbits given albumin in distribution but in timing, since they were most widespread and acute at 1 week and were healing at 2 weeks after injection. Moreover, lesions were observed in almost every animal. 3. Results of immunological studies were consistent with the interpretation that the pathological lesions were due to an antigen-antibody reaction in the tissues, as shown by the following: (a) Acute lesions were only observed when antigen was present and before antibody appeared in the circulation. (b) Healing of lesions was only observed (with one exception) when antigen had almost or completely disappeared from the circulation, usually with the appearance of antibody. (c) There was a correlation between the rapidity of evolution of the lesions and the rapidity with which the antigen disappeared from the circulation. (d) There was a rough correlation between the proportion of animals showing lesions and the proportion developing antibodies after the injection of a particular protein solution.