THE EFFECTS OF MICROBIAL INFECTION ON COMPLEMENT

Micro-organisms can activate complement via the classical or alternative pathways. Following this event, peptides are generated that increase the number of circulating leukocytes, promote adherence of leukocytes to vascular endothelium, and attract phagocytic leukocytes to the site of microbial invasion. Having arrived at the focus of the original infection, these cells then recognise (by their C3b receptors), ingest, and kill the invading micro-organisms. In some instances, killing may not even require phagocytes because certain micro-organisms, especially Neisseria sp. (discussed later), may be killed by the action of complement alone. These bacteria are susceptible to lysis by the terminal attack sequence, C5b-9, that is activated by either the classical or the alternative pathways.

Nevertheless, an important determinant of the pathogenicity of many bacterial strains is the ability to resist complement-mediated destruction. Various mechanisms exist by which a bacterium or other microorganism could avoid attack via the complement cascade:

The surface of the microorganism could have a surface configuration such that the alternative pathway is not directly activated (136). Antibody would be required to initiate opsonisation, affording the microorganism a considerable degree of protection. If the surface of the organism were a poor immunogen, or was marked by host components, the microorganism would be afforded a very high level of protection.
The surface of the organism could activate complement, however, it could afford few attachment sites for the opsonically active complement proteins. A similar effect would be achieved if the surface components to which complement components bind were shed or if structures, such as the capsule, sterically blocked the opsonically active protein fragments, preventing them from binding to their specific receptors on phagocytic cells (137,138).
Proteolytic enzymes, or other molecules such as sialic acid, at the micro-organisms surface could destroy, or inactivate, the opsonically active proteins (139). It is even conceivable that the micro-organisms' surface could facilitate binding and function of the normal serum control proteins which produce loss of opsonic activity.
The surface of the microorganism could be modified or thickened so that the lytic components of complement could be activated at some distance from the critically important lipid bilayer. In this case, although all of the components of the attack mechanism would be activated, lysis would not ensue (140).

Many gram-negative bacteria are killed after treatment with normal serum (141). Gram positive bacteria are less sensitive than gram-negative bacteria to direct killing, although gram-positive cocci are opsonised by the action of serum mediated by antibodies and complement (142,143). Normal sera exhibit bactericidal and bacteriolytic properties against some gram-negative strains; whereas, other gram-negative strains are serum resistant. It has been found, from numerous experiments, that most of the smooth strains of gram-negative bacteria are serum resistant; whereas, the corresponding rough forms are extremely serum sensitive (144,145,146). These investigations provided evidence that the composition of the bacterial surface may influence the reaction of the bacteria with the lytic system (147). The bacteriolytic properties of serum are mediated by the deposition or insertion of the assembled terminal proteins of the complement cascade, C5b-9 (the MAC), into the bacterial envelope. The antibody-dependent activation of the classical complement pathway as well as activation of the alternative pathway by bacteria has been extensively studied. However, several strains are rapidly killed in nonimmune sera. Furthermore, it has been reported that C1 is absorbed to Mycoplasma pneumoniae in the absence of antibodies; the direct interaction with C1 and the activation of the classical complement cascade had even more biological consequences for these bacteria than did activation of the alternative pathway(148). Antibody-independent interaction of C1 with bacteria and bacterial membrane constituents is a common phenomenon Leading to the activation of the complement system and subsequently to the killing of these bacteria.