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The Complement System - Edited

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16 views4 pages

The Complement System - Edited

Uploaded by

Wasana Mendis
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd
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The Complement System

The term complement refers to the ability of some non-specific proteins in normal human serum
to complement , such as Augment the effects of the component of the immune system such as
antibodies.

Properties of complement system


• Extremely powerful
• Comprises of rapidly acting glycoproteins, pro enzymes etc.
• Exists in plasma in an inactive stage.
• Heat liable – therefore, inactivates when the serum is heated to 56C for 30 minutes.
• These glycoproteins are synthesized primarily by liver cells, macrophages.
• Complement usually binds to only the Ag – AB complex.

Nomenclature
• Complement proteins are named after “C” and a “Number” which ranges from C1 – 9
[Remains inactive in the plasma]
• Activation = All the complement proteins between C1 – 9 get activated once they are
cleavage / broken by proteolysis into peptide fragments.
• Fragments are designated as “a” and “b” which are represented in lower keys.
• In most of the complement proteins, the large fragment is named as “b” and small
fragment as “a” [Except for C2]
• In C2, the fragments are named the opposite way around. [Large fragment as “a” and
small fragments as “b”.

Complement activation.

Complement activation occurs through 3 pathways.

Complement activation

Classic Alternative
Lectin Pathway
Pathway Pathway
Alternative and lectin pathways are important in the innate immunity of the host when its
infected by microorganisms for the first time, as the antibodies required to activate the classical
pathway are not present.
Activation of classical pathway requires Antigen – Antibody complexes.
All 3 pathways ultimately activate C3. [Breaks into C3a and C3b fragments]

Classic pathway of complement activation

The classical pathway is a chain of events in which complement components react in specific
sequences as a cascade resulting in cell lysis. It is activated by antibody bound to antigen but
never by native or free antibody.
The classical pathway of complement activation usually begins with the formation of soluble
antigen–antibody complexes (immune complexes) or with the binding of antibody to antigen on
a suitable target, such as a bacterial cell.
Following the formation of Ag – Ab complex, following cascade of reactions occur to activate
the complement leading into final results of cell lysis.
Step 1
The classic pathway starts with the activation of C1, which is composed with 3 sub particles,
C1q, C1r and C1s.

To activate C1, it has to be bound to at least two adjacent antibodies of Ag – Ab complexes and it
binds to the Fc fragment of the two Ag – Ab complex.
Step 2
When C1q bind to the Fc fragments of the Ag – AB complex in the presence of Ca+ ions, C1s
gets activated, and C1s, Splits C4 in to C4a and C4b.
C4a has an anaphylatoxin activity. Hence, C4b binds to the ell membrane / cell surface of the
antigen / bacterial cell.

C4b in the presence of Mg+2 ions attracts C2 and C1s splits C2 into C2a [ Large fragment] and
C2b [Small fragment]. C2b diffuses away, and C2a Remains attached to C4b.
The remaining C4b2a complex possess an enzymatic activity which is called as C3 convertase.

Step 3
C3 convertase converts C3 into its active form [ Splits C3 into C3a and C3b].
1 C3 convertase molecule has the ability to generate about 200 C3b molecules.
What is the significance of this C3b?
Both C3b and C4b cells have the ability to bind to C3b / C4b receptors that almost all the host
body cells, specially the phagocytes has in their surface.
Some C3b binds to C4b2a complex to form C4b2a3b complex which is called as C5 convertase.
C5 Convertase breaks C5 into two. C5a – diffuse away, and C5b – attached C6, and other
remaining complement proteins to form MAC [Membrane Attack Complexes] which attack and
destroy the antigen.
Alternative Pathway of Complement Activation

The initial component of the alternative pathway involves four serum proteins: C3b, factor B,
factor D, and properdin.
Step 1
Initially, in the presence of Mg+2 ions, C3b binds with Factor B and forms C3bB complex.
Step 2
In the presence of Factor D / C3 Proactive convertase, C3bB complex is cleaved in to two
fragments, C3bBa and C3bBb [C3bBb possess the activity of C3 convertase].
Step 3
Since C3bBb is less stable, it binds with Properdin to be stabilize [ C3bBbP]
Stable C3bBbP cleaves C3 into “a” and “b” fragments and binds with “b” fragment which
possess the activity of C5 Convertase.
With the activity of C5 Convertase, C5 will be cleaves and similarly as discussed above in
classic pathway, the MAC will be formed and the antigen will be killed.

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