Nephrotoxic serum nephritis was studied in rats receiving variable amounts of kidney-fixing antibody and active or passive immunization to the heterologous gamma globulin of the species supplying the nephrotoxic antibody. Rats injected with a moderate to a large amount of kidney-fixing antibody (180 to 380 µg) and immunized to the heterologous gamma globulin developed a more severe nephritis than rats receiving similar amounts of antibody without further immunization. Rats injected with minimal amounts of kidney-fixing antibody (2 to 45 µg) and immunized to the heterologous gamma globulin developed a moderate nephritis in contrast to rats receiving similar amounts of antibody without further immunizations which showed no evidence of renal injury. In the rats receiving small doses of kidney-fixing antibody and immunization to the heterologous gamma globulin a lag period existed between the appearance of circulating antibody and kidney-fixed host antibodies and the appearance of renal injury. This delay apparently reflects the need for a continuing antigen-antibody reaction for some time in order to produce detectable injury with the small amounts of reactants involved. From these data it appears that, in the presence of excess circulating antibody, antigens occupying at most a few per cent of the glomerular capillary surface can provide an antigen-antibody interaction which will over a period of time cause detectable morphological and functional alterations of the glomerulus.

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