On the Mechanism of Immune-Adherence

INTRODUCTION Immune-adherence (IA) has been described as a specific immunological reaction wherein microorganisms or other particulate antigens sensitized with antibody (Ab) and complement (C') become attached to the surface of human or monkey erythrocytes." Certain practical advantages of IA noted in recent studies have emphasized the necessity for an understanding of the fundamental nature of the reaction. For example, the marked sensitivity of IA permits the detection of Ab concentrations as low as .01 to .005 p,g. Ab nitrogen (N) per ml. of serum"; a wide range of bacteria,1 "' viruses," ' and soluble antigens,' react in IA; and some applications of IA as a diagnostic test for syphilis"' have been reported. The technique for measuring IA has been simplified considerably by the development of a hemagglutination assay.'" Also, there is evidence that the attachment of bacteria to erythrocytes enhances phagocytosis of the microbes in vitro. This latter observation, coupled with the demonstration that IA occurs in uivo, has suggested a possible role of erythrocytes in defense of the host against infectious agents.' A final feature of some practical importance concerns the observation that C' in human serum is as active as guinea-pig C', e.g., 1 ml. of normal human serum diluted to 1/400 ± 10 per cent provides adequate C' for IA with a variety of antigens. Reproducible reactivity at such high serum dilutions provides a latitude for measurement of decline in disease states which often was difficult to detect by the classical hemolytic assay using sheep erythrocytes and rabbit antiserum wherein C' reactivity was lost at dilutions of human serum exceeding 1/40 or 1/60. The use of IA in studies of human C' has demonstrated a definitive requirement for both These observations have stimulated our efforts to comprehend the quantitative aspects of IA and in particular the nature of the bond established between the sensitized particulate antigen and the normal erythrocyte. The latter has proved elusive to date but during the course of our investigation conditions have been defined under which two different reactions occur which mimic IA in the final result. These two phenomena tentatively have been termed "acid-adhesion" and "C'-dependent mixed aggregation" and are described in this and the following paper, respectively. With attention to detail, it is simple to differentiate these three reactions, all of which are influenced by both Ab and C'. The importance of such differentiation is emphasized by the recent report of …