Immune adherence was described by Nelson (1953)[1] for an in vitro immunological reaction between normal erythrocytes and a wide variety of microorganisms sensitized with their individually specific antibody and complement; erythrocytes were observed to adhere to microorganisms.[1] It was later recognized to occur in vivo.[2]
The phenomenon is now resolved as a complement-dependent binding reaction of erythrocytes to microorganisms where specific antibodies are engaged in the process.[3] The reaction process is as follows: any microorganisms are bound with their specific antibodies, if they are produced, which activate the classical pathway of the complement system. The cascade begins to work from C1 to C3b through C4b, C3b being further transformed to iC3b (inactive derivative of C3b), all of which, C4b and thereafter, remain to bind to the surface of the microbe. Because primate erythrocytes express complement receptor 1 (CR1) on their surface and having binding specificity to C4b, C3b, or iC3b, erythrocytes accumulate on the microbe via CR1-complement binding.[3][4]