2. What is complement system?
• Complement system consists of series of
proteins which complement or augment the
function of Antibodies and other cells of
innate immunity like Macrophages.
• The complement system can be brought into
action by antibodies generated by
the adaptive immune system.
4. Source for complement proteins.
• Liver cells- more than twenty complement
proteins (C1,C2 etc…)
• They are produced in liver and are released
into circulatory system as inactive
complement proteins.
5. Other sources for complement proteins
productions:
- Macrophages,
- Complement Protein 1 – C1- produced by GIT
mucosa.
6. Function of Complement Proteins.
• It is part of the innate immune system
(Humoral Immunity).
• They Complement the immune system and
the inflammatory function.
8. THE CLASSICAL PATHWAY
The classical pathway is initiated by:
- Antibodies (IgM or IgG) binding to the
Pathogen.
- C1 binding to the Fc portion of Antibody
9. • The C1 is a complex protein made of q,r,s
molecules.
C1
C1q C1r C1s
10. • When C1q molecule binds to antibodies, its C1rs
molecules splits C4 and then C2, producing C4a, C4b,
C2a, and C2b.
• C4b and C2b bind to form the classical pathway C3-
convertase (C4b2b complex), which promotes
cleavage of C3 into C3a and C3b.
• C3b later joins with C4b2b to make C5 convertase
(C4b2b3b complex).
11. • The C5 convertase enzyme then cleaves C5 to C5a, a
potent anaphylatoxin, and C5b.
• The C5b then recruits and assembles C6, C7, C8 and
multiple C9 molecules to assemble the Membrane
Attack Complex (MAC).
• This MAC creates a hole or pore in the membrane
that can kill or damage the pathogen or cell.
13. C5b
C9C8
C7
C6
C9
c
C9
C
9 C
9
C9
MEMBRANE ATTACK COMPLEX
MAC is the cytolytic endproduct of the
complement cascade; it forms a
transmembrane channel, which
causes osmotic lysis of the target cell.
Macrophage cell types help clear
complement-coated pathogens.
14.
15. THE ALTERNATIVE PATHWAY
• The alternative pathway does not rely on pathogen-
binding antibodies like the classical pathway.
• In alternative pathway the C3 molecule directly binds
to the antigen of the pathogen and it cleaves to C3b
and C3a.
• The surface-bound C3b may now bind factor B to form
C3bB.
• This complex will be cleaved into Ba and Bb.
• Bb will remain associated with C3b to form C3bBb,
which is the alternative pathway C3 convertase
16. • Once the alternative C3 convertase enzyme is formed
on a pathogen or cell surface, it may bind covalently
another C3b, to form C3bBbC3b, the C5 convertase.
• This enzyme then cleaves C5 to C5a, a
potent anaphylatoxin, and C5b.
• The C5b then recruits and assembles C6, C7, C8 and
multiple C9 molecules to assemble the Membrane
attack complex (MAC).
• This creates a hole or pore in the membrane that can
kill or damage the pathogen or cell.
20. • The complement system has the potential to be
extremely damaging to host tissues, meaning its
activation must be tightly regulated.
• The complement system is regulated by complement
control proteins, which are present at a higher
concentration in the blood plasma than the
complement proteins themselves.
REGULATION
21. • Some complement control proteins are present on
the membranes of self-cells preventing them from
being targeted by complement.
• One example is CD59, also known as protectin, which
inhibits C9 polymerisation during the formation of
the membrane attack complex.
• The classical pathway is inhibited by C1-inhibitor,
which binds to C1 to prevent its activation.
• C3-convertase can be inhibited by Decay accelerating
factor (DAF).
22. PATHOLOGY OF COMPLEMENT SYSTEM
Complement deficiency:
• Asthma
• Systemic lupus erythematosus
• Glomerulonephritis
• Inflammatory bowel disease
• Rejection of transplanted organs.
• Autoimmune disorders.
23. • Deficiencies of the terminal pathway predispose to:
• Autoimmune and infections (particularly Neisseria
meningitidis, due to the role that the membrane
attack complex ("MAC") plays in attacking Gram-
negative bacteria).
• Infections with N. meningitidis and N. gonorrhoeae are
the only conditions known to be associated with
deficiencies in the MAC components of complement.
• People with MAC deficiencies experience recurrent
infections with N. meningitidis.
