Histological and Serological Sequences in Experimental Hypersensitivity

Abstract

The histological and serological changes in animals made experimentally hypersensitive to foreign proteins have been separately studied by many investigators. It does not fall within the scope of this report to review the extensive literature dealing with these subjects. It is our purpose to attempt to correlate the sequences in the development of definite tissue changes with concomitant serological studies of the levels of antigen and antibody. The demonstration by Rich and Gregory (1), that a single large injection of heterologous serum may produce marked vascular lesions in rabbits not sensitized previously, has provided an experimental technique adaptable to such studies.Hektoen and Cole (2), Cannon and Marshall (3), and others have pointed out the importance of using only highly purified and well characterized proteins in studies on the fundamental nature of immune reactions. The methods for the fractionation of plasma proteins recently developed in the Department of Physical Chemistry of the Harvard Medical School (4-10) have made available many of the proteins of both human and bovine blood plasma in states of greater purity and in larger amounts than could readily have been obtained by previous methods. The use of these materials has provided a new approach to studies of the reactions of hypersensitivity as well as to many other problems in biology and in clinical medicine. Research and Development. The molecular weight, as determined by osmometric methods and by analysis in the ultracentrifuge was 69,000. The albumin was electrophoreticaUy pure and impurities which could be detected by serologic methods were less than 0.05 per cent. The albumin was used in 25 per cent solution in water especially distilled for intravenous use, to which was added sodium bicarbonate (0.375 gln. per 100 cc. solution) and sodium chloride Martials

Glomerulonephritis Induced in Sheep by Injections of Heterologous Glomerular Basement Membrane and Freund's Complete Adjuvant

“…Most attempts to produce experimental animal nephritis by immunological models have centered chiefly on the production of nephritis by single or repeated intravenous injections of foreign protein (15)(16)(17), antigen-antibody complexes (18), or anti-kidney antibodies (13). Heteronephrotoxic sera have been considered to be highly species specific (19,20), but Steblay and Lepper (21) have shown that rabbit antihuman glomerular basement membrane serum will produce nephritis in dogs.…”

Renal Disease Following Prophylactic Inoculation

“…These are not distinguishable histologically from lesions induced by soluble antigen-antibody complexes [4], Both the fluorescent antibody studies on the renal biopsy tissue and the serial plasma immunoglobulin estimations, serum plasma and complement estimations are in favour of complex disease. There is some evidence that the molecular size of immune complexes determines the site of their deposition in the vascular tree [2,6]. In the kidneys the heavier immune complexes are more likely to be deposited in the glomeruli whereas the lighter complexes will be deposited in the arterial walls.…”

Serum Sickness – 1957

“…Hawn and Janeway (17) made similar studies in rabbits using purified preparations of bovine serum albumin and bovine gamma globulin instead of crude serum which contains a mixture of many different proteins. These two chemically and immunologically different serum protein antigens produced quite different reactions.…”