The Alternative Pathway

This chapter describes the alternative pathway. The activation of complement via the alternative pathway provides a natural system of defense against infectious agents, because it is capable of neutralizing a wide variety of potential pathogens in the absence of specific antibodies. The alternative pathway, thus, differs from the classical pathway in that it provides an immediately available line of defense that does not require prior immunization. It resembles the classical pathway in that both systems result in the activation of the membrane attack or terminal pathway of complement. The six plasma proteins involved in the alternative pathway recognize a wide variety of potential pathogens within minutes after such organisms come in contact with plasma. Organisms sensitive to attack by the alternative pathway include bacteria, fungi, a number of viruses, virus-infected cells, certain tumor cell lines, parasites such as trypanosomes, and erythrocytes from patients with paroxysmal nocturnal hemoglobinuria. The activation process of the alternative pathway differs from that of the classical pathway in several ways. Instead of attacking targets that have been specifically identified by antibody, the alternative pathway uses a shotgun approach. The amplification reaction of the alternative pathway involves three proteins: C3, factor B, and factor D.