4.3 Soluble components of innate immune system

The soluble components of innate immune system bind with the microbes and help in their phagocytosis by the cells of innate immunity. They may sometimes involve in direct killing of the pathogens by promoting the inflammatory response.

4.3.1 Complement system

This system consists of many plasma proteins that help in opsonization of the microbial antigens to promote the recruitment of phagocytic cells. It involves a cascade in which an inactive zymogen is converted into active proteases and many proteolytic products.

First step in the activation of complement system is the recognition of the foreign substance and that occurs by three different pathways

1.  Classical pathway

2.  Alternate pathway

3.  Lectin pathway

Classical pathway was named as it was discovered first and uses the plasma protein C1q to detect antibody bound over the surface of microbes. Following the binding, C1q starts the cascade (figure 4.2) which leads to lysis of the microbes. Alternate pathway is triggered with a protein called C3 which recognizes the lipopolysaccharides present in the bacterial cell. Lectin pathway is triggered by the mannose binding lectin that recognizes the mannose residues present in the microbes.

Recognition of antigens by any of these pathways converts C3 into C3a and C3b with the help of C3 convertase. C3b binds with the microbial antigen while C3a stimulates the release of inflammatory cytokines. C3b activates the C5 convertase to convert C5 into C5a and C5b. C5a is a chemoattractant while C5b initiates the formation of complex with other complement proteins C6, C7, C8, and C9. This sequential cascade leads to formation of membrane attack complex which causes lysis of the cell.