Classical complement pathway

The classical complement pathway is a component of the innate immune system. The innate immune system serves as a constant non-specific defense against foreign pathogens including bacteria, viruses, fungi, and parasites. Complement is a part of that system but it cannot act independently. Classical complement as discussed here relies on the actions of B cells to produce antibodies specific to different pathogens, as well as other components of the innate immune system such as Mast cells or Macrophages. It is an important aspect of our immune system and malfunction of complement can result in a compromised immune system. Complement deficiency has also been linked with autoimmune diseases and immunosuppression. Without complement we are unable to utilize the full strength of our immune system as macrophages and mast cells rely on it to phagocytose and release histamine respectively. While both of these cells are capable of functioning independently, the signal amplification that complement provides greatly increases their effectiveness.

The classical complement pathway functions as a part of the complement system and leads to complement activation via the binding of antibodies to antigen. Both the IgM and IgG antibody isotypes are capable of initiating complement activation. This initiation step then leads to the recruitment of other proteins in order to form the c3 convertase protein complex. C3-convertase hydrolyzes C3 resulting in the complement cascade causing signal amplification and further complement activation. The following steps in the pathway are similar to those initiated by the lectin pathway and alternative complement pathway. C3b binding results in further signal amplification and cleavage of C5, which leads to the formation of the Complement membrane attack complex, eventually forming a pore in the membrane of the target and inducing cell lysis and death. The classical pathway of complement activation is only one of three methods of activation, the others being the alternative complement pathway and the lectin pathway.

The critical distinction between classical complement and other forms of complement is the role of antibodies to complement activation. Antibodies are essential to effective complement response in this pathway. The only antibodies capable of binding are IgG and IgM. It takes two units of IgG or one unit of IgM to trigger complement activation. IgM is thought of as more effective at activating complement (IgG4 cannot bind, but the other three IgG types can).

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