Studies on Antigen-Antibody Complexes

Abstract

In vivo-formed antigen-antibody complexes cause transient glomerulonephritis and vasculitis in experimental animals when appropriate antigens are administered to unimmunized animals in a single dose (1, 2). Similar antigens administered in multiple doses induce chronic disease (1, 3). Antigen, antibodies, and complement components have been demonstrated in lesions produced in this manner. Furthermore, antigen-antibody complexes have been shown as causative agents of glomerulonephritis in human systemic lupus erythematosus (4), acute poststreptococcal glomerulonephritis (5), malaria (6), and other conditions. However, in experimental models and in human diseases, the characteristics of immune complexes that become entrapped by vascular and glomerular basement membranes to cause disease are not fully understood. In addition, detailed descriptions are not available on the characteristics of immune complexes that form in vivo from the native antibodies and the antigens that are introduced experimentally in animals or by disease processes in man. Similarly, quantitative information on the fate of such complexes is lacking.When antigens are administered to immunized animals in small doses or if immune complexes are given to nonimmunized animals, the immune complexes are removed rapidly in part by the reticuloendothelial system (7, 8). Weigle (9) showed that if intravenously injected antigen-antibody complexes are prepared at equivalence or in slight antigen excess, they are quickly removed from the circulation of rabbits and that similar complexes prepared in large antigen excess persist longer. He concluded that the size of the complexes played a major role in their clearance from the circulation. Cochrane and Hawkins (10) also indicated that immune complexes greater than 19S are quickly removed from the circulation of guinea pigs and that small antigen-antibody complexes persist in the circulation. These investigators suggested that the immune complexes had to exceed a certain critical size and that vascular permeability had to be increased before complexes were entrapped by vascular or glomerular basement membranes. The half-life of the complexes that are rapidly removed has not been well defined and the role of the complement-fixing ability of these complexes has not been characterized fully.

CR1 genotype and haplotype involvement in coronary artery disease: The pivotal role of hypertension and dyslipidemia

“…Circulating immune complexes cause inflammation of the vessel wall and accelerate atherosclerosis both in experimental animal models and in humans. Repeated injection of protein antigens leads to the formation of circulating immune complexes and to the acceleration of the spontaneous and diet-induced atherosclerotic process in both rabbits and mice (28,29). Premature atherosclerosis is also observed in patients with chronic immune complex formation due to inflammatory disorders (30,31), and there is an increased incidence of premature myocardial infarction in patients with systemic lupus erythematosus and autoimmune diseases characterized by circulating immune complexes (32).…”

Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy

“…Kaetzel et al 13 have reported on active transport of immune complexes containing pIgA (pIgA-IC) across the epithelial cells by the same pIgR-dependent mechanism that normally applies to free pIgA. Several investigators [14][15][16][17][18] have emphasized the importance of the pIgR-dependent system for transport of pIgA-IC, rather than the mononuclear phagocyte system, which mediates a major clearance pathway of immune complexes in circulation. Thus, the decreased pIgR expression observed in ddY High mice may potentially not only result in serum pIgA elevation but also serum pIgA-IC accumulation.…”

Clq and immune complexes in liver cirrhosis sera.

“…In order to explain the increased levels of circulating immune complexes in advanced liver diseases, two possibilities should be considered; increased formation and decreased hepatic clearance, that is, the disturbance of function of the reticuloendothelial system (Mannik et al 1971; Thomas et al 1978). The presence of serum Clq in higher concentrations might suggest the exemption of its consumption by binding with immune complexes in vivo, although immune complexes were detected by means of Clq radioimmunoassay.…”