Consequences of Complement Activation – Effector Functions

The MAC and other complement by-products formed during activation of various pathways augments the immune response in many ways as follows. These are known as effector functions of complement products.

1. Cell lysis by MAC

MAC damages cell membrane by making pores or channels in it and allowing the free passage of various ions and water in to the cell. This ultimately leads to cell death. Bacteria, enveloped viruses, irreversibly damaged cells, cancerous cells etc are killed by this mechanism commonly referred to as complement mediated cell lysis.

Gram positive bacteria, which are protected by their thick peptidoglycan layer, bacteria with a capsule or slime layer around their cell wall, or non-enveloped viruses are less susceptible to lysis.

2. Inflammatory Response

C3a, C4a and C5a are called anaphylotoxins. They bind to receptors on mast cells and induce its degranulation leaing to release of histamine and other pharmacologically active mediators of inflammation. They cause vasoconstriction and increase in vascular permeability. Along with the C5b67, they also induce the migration of neutrophils and monocytes to the site of complement activation. This leads to an inflammatory response which is a local protective response.

3. Opsonization

C3b and C4b act as major opsonins that coat the immune complexes and particulate antigen. Phagotytic cells express receptors (CR1, CR3 and CR4) for complement components (C3b, C4b etc.) and are able to bind the complement coated antigen and enhance its phagocytosis. C5a augments this process by enhancing the CR1 expression on phagocytes by 10 folds.

4. Viral Neutralization.

Complement plays a very important role in viral neutralization in many ways:

  • Most viral particles bind to their serum antibody and form particulate immune complex which stimulates the classical pathway. Many viruses are also capable of activating the alternative and lactin pathway in the absence of antibody. So, the MAC is able to destroy the viruses.
  • C3b helps in the formation of viral aggregates by acting as opsonin and thus decrease the net number of infective viral particles. This effect is enhanced in the presence of serum antibody.
  • Complement products also coat the viral particles. This coating neutralizes the viral infectivity by blocking its attachment to target cell and enhancing its phagocytosis by macrophages through complement.
  • Complement cytolyse most enveloped viruses causing fragmentation and disintegration.

5. Solublization of Immune Complex

C3b plays an important role in removing immune complex from the blood. its binding to complexes facilitates their binding to CR1 on RBCs. Though CR1 are present in higher number is granulocytes than the RBCs, but because of much larger number of RBCs than granulocytes in blood, RBCs account for the 90% of the total CR1 in blood. Immune complexes bound to the RBCs are taken to liver and spleen where they are phagocytoed after seperation from RBCs.