Complement System


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Complement System

Resolving to the use mercenaries by a General to help heighten his defensive line, while fighting an opposition is a very good strategy for winning battles.  Complement proteins are mercenaries produced regularly by the liver cells and employed in fighting infections in the body.

The complement system is a set of nine major proteins (C1, C2, C3, C4, C5, C6, C7, C8 and C9).
These proteins migrate and mix with the blood, lymph and extracellular fluid where they help fight and destroy pathogens.

Complement proteins are enzymatic in nature and circulate in the body in inactive form.

They are either activated upon encounter with infections (or pathogens) in the body or by antigen-antibody complex.

Complement proteins are activated in three pathways:

  1. The Classical Pathway
  2. The Lectin Pathway
  3. The Alternative Pathway

Classical Pathway

classical pathwayThe binding of antibodies (IgG or IgM) to the antigens which are mainly bacteria ( i.e antigen-antibody complex) trigger the activation of complement proteins, mainly: C1 and C4 and subsequently lead to the activation of other complement proteins in a cascade reaction.

Alternative Pathway

Alternative pathwayIn contrast to the classical pathway, the alternative pathway involves the B, D, H and I factors that interacts with each other and with C3b to form C3b convertase (C3bBb) which subsequently actives other C3 in a cascade reaction.

Lectin Pathway

Lectin PathwayThis pathway is independent of antibodies involved in the classical pathway and factors of the alternative pathway. Activations of complement proteins in this pathway require the binding of Mannan-Binding Lectins (MBL) to mannose (sugar) on the surfaces of microorganisms. This subsequently leads to a cascade reaction of the classical pathway.

The activation of these proteins leads to 3 major consequences:

  1. Opsonization and Phagocytosis
  2. Inflammation
  3. Cytolysis (Membrane attack)

Opsonization and Phagocytosis

opsonization and phagocytosisThe complement proteins (C3b) bind to the antigens and present it to phagocytes which engulfs and digest them.


InflammationC3a and C5a are known to induce swelling of tissues at the site of infection and attract  macrophages and neutrophils that does engulf, eat up and eliminate the antigens.


Membrane Attack ComplexThis is also known as the lysis of target cells. Complement proteins such as C5b, C6, C7 and C8 and C9 assembles at the membrane of cells to form “Membrane-attack complex (MAC)” which creates pores on the membrane of target cells and subsequently leading to their disruption.

Nomenclature of the complement system

  • Complement proteins are usually designated by capital letter “C” followed by a number based on their order of discovery from C1- C9 (i.e C1, C2, C3, C, C4, C5, C6, C7, C8, C9).
  • When a protein is broken into two, the resulting fragment is designated by adding a lower case suffix i.e “a” or “b”.

Where suffix “a” represent the smaller fragment

Suffix “b” represents the larger fragment

For example

Complement NomenclatureHowever, there exists an exception. In C2, the larger fragment is C2a while the smaller fragment is C2b

See also introduction to immunology, immunology: first line of defense, immunology: second line of defense

Cite this article as: Fagbohun, S.O., "IMMUNOLOGY: UNDERSTANDING THE COMPLEMENT SYSTEM," in ATG Ventures, 09/03/2019,

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