Classical Pathway of Complement Activation


The complement system is a part of the innate immune system that consists of a series of proteins that circulate in the blood and help to fight against infections. The complement system can be activated by three different pathways: the classical pathway, the alternative pathway, and the lectin pathway. Each pathway leads to the formation of a membrane attack complex (MAC) that can lyse target cells such as bacteria, viruses, or parasites.

The classical pathway of complement activation is the oldest and most well-studied pathway. It was first discovered in 1895 by Jules Bordet, who observed that serum could kill bacteria in the presence of antibodies. The classical pathway is mainly triggered by the binding of antibodies to antigens on the surface of pathogens or foreign cells. This forms an antigen-antibody complex that activates the first component of the complement system, C1. C1 then initiates a cascade of proteolytic reactions that involve other complement components such as C2, C3, C4, and C5. The end result is the formation of a MAC that can insert into the membrane of the target cell and create pores that allow water and ions to enter and cause cell lysis.

The classical pathway of complement activation plays an important role in immunity and inflammation. It can enhance the opsonization and phagocytosis of pathogens by coating them with C3b and C4b fragments. It can also recruit and activate inflammatory cells such as neutrophils and mast cells by releasing anaphylatoxins such as C3a and C5a. Furthermore, it can regulate the adaptive immune response by modulating the activation and differentiation of B cells and T cells.

In this article, we will discuss the activators, steps, and regulation of the classical pathway of complement activation in more detail. We will also highlight some of the clinical implications and disorders associated with this pathway.