78 Steps Health Journal

The Complement System Clears Immune Complexes from Circulation

The importance of the complement system in clearing immune complexes is seen in patients with the autoimmune disease systemic lupus erythematosus (SLE). These individuals produce large quantities of immune complexes and suffer tissue damage as a result of complement-mediated lysis and the induction of type II or type III hypersensitivity (see Chapter 16). Although complement plays a significant role in the development of tissue damage in SLE, the paradoxical finding is that deficiencies in C1, C2, C4, and CR1 predispose an individual to SLE; indeed, 90% of individuals who completely lack C4 develop SLE. The complement deficiencies are thought to interfere with effective solubilization and clearance of immune complexes; as a result, these complexes persist, leading to tissue damage by the very system whose deficiency was to blame.

The coating of soluble immune complexes with C3b is thought to facilitate their binding to CR1 on erythrocytes. Although red blood cells express lower levels of CR1 (~5 X 102 per cell) than granulocytes do (~5 X 104 per cell), there are about 103 red blood cells for every white blood cell; therefore, erythrocytes account for about 90% of the CR1 in the blood. For this reason, erythrocytes play an important role in binding C3b-coated immune complexes and carrying these complexes to the liver and spleen. In these organs, immune complexes are stripped from the red blood cells and are phagocytosed, thereby preventing their deposition in tissues (Figure 13-14). In SLE patients, deficiencies in C1, C2, and C4 each contribute to reduced levels of C3b on immune complexes and hence inhibit their clearance. The lower levels of CR1 expressed on the erythrocytes of SLE patients also may interfere with the proper binding and clearance of immune complexes.

Electron micrographs of negatively stained prepara- [From N. R. Cooper and G. R. Nemerow, 1986, in Immunobiology of the tions of Epstein-Barr virus. (a) Control without antibody. (b) Antibody- Complement System, Academic Press.] coated particles. (c) Particles coated with antibody and complement.

FIGURE 13-13

Electron micrographs of negatively stained prepara- [From N. R. Cooper and G. R. Nemerow, 1986, in Immunobiology of the tions of Epstein-Barr virus. (a) Control without antibody. (b) Antibody- Complement System, Academic Press.] coated particles. (c) Particles coated with antibody and complement.

FIGURE 13-13

BL00D

BL00D

Soluble immune complex

Soluble immune complex

Complement activation

Complement activation

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