Notes on Complement system: The troop of serum proteins in defence

Complement system consists of approximately 20 serum proteins that interact with each other and other components of immune system to eliminate the intruder. These are proteins that work as a team, one activating the other or as a biological cascade.

Site of synthesis: liver

Mode of action:The three major effect of complement are

• lysis of pathogen, tumor cells and allografts
• production of mediators that attracts neutrophils to the site of inflammation
• opsonization that is enhancement of phagocytosis.

Activation:

Several complement components are enzyme precursors or proenzymes which are cleaved to form active enzymes. These systems are activated either by antigen antibody complexes or by toxins or antigenic fragments.

Sequential activation of complement components occurs via one of two pathways:

Classical pathway: Here complement system is activated by antibodies bound to pathogen surface or antibody-antigen complexes, thus involved in specific and acquired immunity. Read more

Alternative pathway:Sometimes microorganisms or its toxins can directly activate complement system, which is an innate and non-specific reaction. Sooner microorganisms are coated by complement molecules leading to its uptake by phagocytosis.  

Once the pathogen has crossed the physical barrier and enters the body, alternative pathway interacts with the microorganism’s  (non-specific immune response). Now let us move into the details of these pathways. Read more

Classical pathway and Alternative pathway

C3b: is the central molecule in the complement cascade in both the pathways.

This protein has 2 major functions:

• It generates C5 convertase, a vital enzyme responsible for the production of membrane attack complex.
• It opsonises (enhancing phagocytosis) bacteria as phagocytes have receptors for C3b on their surface. 

Biologic effect of complement system:

• Cytolysis: Membrane attack complex kills or lyse bacterial cells or tumor cells by creating pores in the membrane. Water entry lead to swelling and lysis of cells
• Chemotaxis: attracting cells of the immune cells to the site. C5a attract neutrophils.
• Anaphylatoxin: C3a, C4a and C5a causes release of inflammatory mediators like histamines.
• Opsonisation: Presence of C3b enhances phagocytic activity of phagocytes. C3b receptors are present on the surface of many phagocytes.
• Enhancement of antibody production: B cell has C3b receptors on its surface. Binding of C3b to its receptors on activated B cells greatly enhances antibody production compared to B cell activated by antigen alone.

In short, complement system plays a major role especially in non-specific immune defence.