Complement components and receptors: deficiencies and disease associations.

The complement system, accessory to many immunological functions, consists of a number of interdependent components and receptors. Numerous in vitro approaches have elucidated the biological role of these components and receptors. However, it is the in vivo "natural" experiments that underscore their importance. The phagocytosis and subsequent digestion of pyogenic bacteria is significantly enhanced by the fixation of the third complement component to the bacterial cell wall. Equally important is the intact expression of a receptor (CR3) for the C3b cleavage fragment. Breakdown in this ligand-receptor interaction due to either C3 or CR3 deficiency leads to pyogenic infection. Interestingly, C3-deficient individuals do not demonstrate leukocytic infiltration at the site of infection. Undoubtedly, this is due to the lack of C5 convertase and failure to produce C5a. CR3-deficient individuals, on the other hand, do demonstrate leukocytosis since the third complement component is functional. C3 deficiency is not necessarily a primary lesion and may be secondary to factor I deficiency. In this case, the C3b fragment, along with factor B, acts as a C3 convertase. Inefficient inactivation of C3b, due to factor I deficiency, leads to the uncontrolled consumption of the third component, resulting in C3 deprivation. It appears that phagocytosis by neutrophils and monocytes followed by enzyme-interaction is not sufficient for destruction of the Neisseria organisms. In addition to this leukocyte activity, an intact membrane attack complex, composed of the late complement components C5, 6, 7, 8, and 9, is required for the lysis of these bacteria. This is supported by findings that individuals deficient in late components are highly susceptible to systemic Neisseria infections. Diseases of an autoimmune nature are frequently associated with a deficiency of one of the early complement components C1, C2, or C4 and a deficiency of erythrocytic CR1 receptors as well. This may suggest that proper interaction between a complement fragment of the immune complex with the complement receptor expressed on the erythrocyte is important for proper management and clearance of the complex. Deficiency of the early complement components would prevent the activation of C3 and the fixation of a resulting C3 cleavage product. In this case, erythrocytes would be unable to participate in the transport of the immune complex to the reticuloendothelial system. Instead, tissue deposition of the complex would occur more readily, contributing to the pathologic process. Provided that the early complement cascade were intact, deficiency of erythrocytic CR1 receptors would contribute to the pathologic response for the same reason.(ABSTRACT TRUNCATED AT 400 WORDS)