Electron Microscopy of Serum Sickness Nephritis

Abstract

The morphology of antigen-antibody reactions in tissues has been amply documented by studies with the light microscope. At the cytological level, however, the intracellular changes elicited by antigen-antibody union have been poorly defined and vaguely located. As an experimental model to study this problem, serum sickness nephritis was selected first, because there was already a fairly large accumulation of data on the electron microscopic anatomy of the kidney which could be used for comparison (1-17), and second, because specific antigen has been shown to be present in the giomerulus by the fluorescent microscopic technique (18). Serum sickness offered the possibility of studying the cellular events in the development of renal lesions. Materials and MethodsSix albino rabbits, weighing between 2.5 and 3.0 kg., were used. Two were controls; four were injected intravenously with 250 rag. of bovine serum albumin (BSA) 1 per kg. of body weight. The BSA was purified, crystallized, and tagged tightly with p~a. The rate of antigen elimination was followed by determining the disappearance of serum radioactivity. Immune elimination occurred in all four animals 11 days after the injection of antigen; two were killed 1 day later and two were killed 2 days later; i.e., 12 and 13 days after antigen administration.It has been shown that during the period of immune elimination of antigen, the glomerular lesions were most extensive and severe (18), while prior to this period glomerular lesions could not be found by fight microscopy. After antigen was completely lost from the circulation, glomerular lesions were diminished in number and severity. Fluorescence microscopy showed antigen only in those glomerufi which were altered. P.-ESIYLTSThe structure of the normal glomerulus is briefly reviewed here to point out certain salient features for comparison with glomeruli of experimental rabbits.The glomerulus (Figs. 1 and 3) is constructed of a network of patent capillaries which communicate with one another by short, narrow channels.

The Nephrotic Syndrome in Secondary Syphilis

“…Basement membrane deposits located in the external portion of the basement membrane, as observed in our case, have been seen in membranous glomerulonephritis of human adults (28, 30), in human acute glomerulonephritis (39), and in the membranous glomerulonephritis produced in rats by "autoimmune nephrosis" (40,41). Deposits in this location are usually seen in acute proliferative (poststreptococcal type) glomerulonephritis (32,39,43), in lupus nephritis (39,44,45), in the glomerulopathy of toxemia of pregnancy (46,47), and in experimental serum sickness nephritis (48). Less numerous electron dense deposits in the inner zone of the glomerular capillary basement membrane were observed in our case.…”

Acute poststreptococcal glomerulonephritis: immune deposit disease.

“…The closest experimental analogue to the lesions in acute poststreptococcal glomerulonephritis is antigen-antibody complex nephritis, as observed by Dixon, Feldman, and co-workers (42)(43)(44)(45). Our own studies (3) and those of Germuth and McKinnon (46,47) support the concept that the lesions of serum sickness reflect the toxicity of these complexes, which are also complement fixing.…”

“…Our own studies (3) and those of Germuth and McKinnon (46,47) support the concept that the lesions of serum sickness reflect the toxicity of these complexes, which are also complement fixing. Light microscopy of the kidney in rabbits with experimental serum sickness shows acute proliferative glomerulonephritis and vasculitis, and electron microscopy reveals swelling and proliferation of the endothelial cells and deposition of electron-dense material adjacent to and within the glomerular basement membrane (42)(43)(44). Ferritinlabeled studies have shown that these deposits contain bovine serum albumin (antigen) and rabbit y-globulin (antibody) (48).…”

Pathogenic Factors in Vascular Lesions of Experimental Serum Sickness

“…Using a modification of the fluorescence method, these immune reactants were seen distributed along the basement membrane. By electron microscopy, alterations in the glomerular basement membrane and occasional small deposits within it have been described in serum sickness (26). Whether these changes are related to the presence of immune reactants has not been determined.…”