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Aamir Ali Khan
Assistant Professor
Department of Pathology
The complement
system
The complement system
A defensive system consisting of over 30 proteins
produced by the liver and found in circulating blood
serum.
Complement kills microbes in three different ways
1. opsonization
2. inflammation
3. Cytolysis
A Cascade system
The complement works as a cascade system.
Cascade is when one reaction triggers another reaction
which trigger others and so on. These types of systems
can grow exponentially very fast.
Cascade activation
Complement proteins are often designated by an
uppercase letter C and are inactive until they are split
into products.
Example: C1
When the products are split they become active. The
active products are usually designated with a lower
case a or b.
Example: C1a and C1b
Two Pathways
The complement pathway can be activated by
either of two different pathways.
Classical pathway (specific immune system)
alternative (non-specific immune system)
The Classical Pathway
The classical pathway is
considered to be part of
the specific immune
response because it relies
on antibodies to initiate it.
C1 becomes activated
when it binds to the ends
of antibodies
The building of a C3 activation complex
Once C1 is activated, it activates
2 other complement proteins,
C2 and C4 by cutting them in
half
C2 is cleaved into C2a and C2b
C4 is cleaved into C4a and C4b
Both C2b and C4b bind
together on the surface of the
bacteria
C2a and C4a diffuse away
C3 Activation complex
C2b and C4b bind together on the
surface to form a C3 activation
complex
The function of the C3 activation
complex is to activate C3 proteins.
This is done by cleaving C3
into C3a and C3b
C3b
Many C3b molecules are produced by the C3 activation complex.
The C3b bind to and coat the surface of the bacteria.
 C3b is an opsonin
 Opsonins are molecules that bind both to bacteria and phagocytes
 Opsonization increases phagocytosis by 1,000 fold.
Bacteria
Opsonins
C3a
C3a increases the inflammatory response by binding to mast cells and
causing them to release histamine
Building the C5 activation complex
 Eventually enough C3b is cleaved that the surface of the bacteria
begins to become saturated with it.
 C2b and C4b which make up the C3 activation complex has a slight
affinity for C3b and C3b binds to them
 When C3b binds to C2b and C4b it forms a new complex referred to
as the C5 activation complex
The C5 activation complex
The C5 activation complex (C2b, C4b, C3b) activates C5 proteins by
cleaving them into C5a and C5b
Many C5b proteins are produced by the C5 activation complex. These
C5b begin to coat the surface of the bacteria.
The function of C5a
C5a disperses away from the bacteria.
Binds to mast cells and increases inflammation.
Most powerful chemotactic factor known for leukocytes
Building the Membrane Attack complex
C5b on the surface of bacteria binds to C6
The binding of C6 to C5b activates C6 so that it can bind to C7
C7 binds to C8 which in turn binds to many C9’s
Together these proteins form a circular complex called the Membrane
attack complex (MAC)
Membrane Attack complex
The MAC causes Cytolysis.
The circular membrane attack
complex acts as a channel in
which cytoplasm can rush out of
and water rushes in.
The cells inner integrity is
compromised and it dies
Overview
The alternative pathway
The alternative pathway is part of the non-specific
defense because it does not need antibodies to initiate
the pathway.
The alternative pathway is slower than the Classical
pathway
Initiation of The Alternative pathway
C3 contains an unstable
thioester bond.
This unstable bond makes C3
subject to slow spontaneous
hydrolysis to C3b and C3a
The C3b is able to bind to
foreign surface antigens.
Mammalian cells contain
sialic acid which inactivates
C3b
Factor B
C3b on the surface of a
foreign cells binds to
another plasma
protein called factor B
Factor D
The binding of C3b to
factor B allows a
protein enzyme called
Factor D to cleave
Factor B to Ba and Bb.
Factor Bb remains
bound to C3b while Ba
and Factor D disperse
away.
The C3 activation complex
Properdin, also called factor P, binds to the C3bBb
complex to stabilize it.
C3bBbP make up the C3 activation complex for
the alternative pathway
The C3 activation Complex
The C3 activation
complex causes the
production of more
C3b.
This allows the initial
steps of this pathway
to be repeated and
amplified
2X106
molecules can be
generated in 5 minutes
C5 activation complex
When an additional C3b
binds to the C3 activation
complex it converts it into
a C5 activation complex.
The C5 activation complex
cleaves C5 into C5a and
C5b.
C5b begins the production
of the MAC.
Overview
Your attitude not your aptitude will
determine your altitude.
Aamir Ali Khan

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The complement system new

  • 1. Aamir Ali Khan Assistant Professor Department of Pathology
  • 3. The complement system A defensive system consisting of over 30 proteins produced by the liver and found in circulating blood serum. Complement kills microbes in three different ways 1. opsonization 2. inflammation 3. Cytolysis
  • 4. A Cascade system The complement works as a cascade system. Cascade is when one reaction triggers another reaction which trigger others and so on. These types of systems can grow exponentially very fast.
  • 5. Cascade activation Complement proteins are often designated by an uppercase letter C and are inactive until they are split into products. Example: C1 When the products are split they become active. The active products are usually designated with a lower case a or b. Example: C1a and C1b
  • 6. Two Pathways The complement pathway can be activated by either of two different pathways. Classical pathway (specific immune system) alternative (non-specific immune system)
  • 7. The Classical Pathway The classical pathway is considered to be part of the specific immune response because it relies on antibodies to initiate it. C1 becomes activated when it binds to the ends of antibodies
  • 8. The building of a C3 activation complex Once C1 is activated, it activates 2 other complement proteins, C2 and C4 by cutting them in half C2 is cleaved into C2a and C2b C4 is cleaved into C4a and C4b Both C2b and C4b bind together on the surface of the bacteria C2a and C4a diffuse away
  • 9. C3 Activation complex C2b and C4b bind together on the surface to form a C3 activation complex The function of the C3 activation complex is to activate C3 proteins. This is done by cleaving C3 into C3a and C3b
  • 10. C3b Many C3b molecules are produced by the C3 activation complex. The C3b bind to and coat the surface of the bacteria.  C3b is an opsonin  Opsonins are molecules that bind both to bacteria and phagocytes  Opsonization increases phagocytosis by 1,000 fold. Bacteria Opsonins
  • 11. C3a C3a increases the inflammatory response by binding to mast cells and causing them to release histamine
  • 12. Building the C5 activation complex  Eventually enough C3b is cleaved that the surface of the bacteria begins to become saturated with it.  C2b and C4b which make up the C3 activation complex has a slight affinity for C3b and C3b binds to them  When C3b binds to C2b and C4b it forms a new complex referred to as the C5 activation complex
  • 13. The C5 activation complex The C5 activation complex (C2b, C4b, C3b) activates C5 proteins by cleaving them into C5a and C5b Many C5b proteins are produced by the C5 activation complex. These C5b begin to coat the surface of the bacteria.
  • 14. The function of C5a C5a disperses away from the bacteria. Binds to mast cells and increases inflammation. Most powerful chemotactic factor known for leukocytes
  • 15. Building the Membrane Attack complex C5b on the surface of bacteria binds to C6 The binding of C6 to C5b activates C6 so that it can bind to C7 C7 binds to C8 which in turn binds to many C9’s Together these proteins form a circular complex called the Membrane attack complex (MAC)
  • 16. Membrane Attack complex The MAC causes Cytolysis. The circular membrane attack complex acts as a channel in which cytoplasm can rush out of and water rushes in. The cells inner integrity is compromised and it dies
  • 18. The alternative pathway The alternative pathway is part of the non-specific defense because it does not need antibodies to initiate the pathway. The alternative pathway is slower than the Classical pathway
  • 19. Initiation of The Alternative pathway C3 contains an unstable thioester bond. This unstable bond makes C3 subject to slow spontaneous hydrolysis to C3b and C3a The C3b is able to bind to foreign surface antigens. Mammalian cells contain sialic acid which inactivates C3b
  • 20. Factor B C3b on the surface of a foreign cells binds to another plasma protein called factor B
  • 21. Factor D The binding of C3b to factor B allows a protein enzyme called Factor D to cleave Factor B to Ba and Bb. Factor Bb remains bound to C3b while Ba and Factor D disperse away.
  • 22. The C3 activation complex Properdin, also called factor P, binds to the C3bBb complex to stabilize it. C3bBbP make up the C3 activation complex for the alternative pathway
  • 23. The C3 activation Complex The C3 activation complex causes the production of more C3b. This allows the initial steps of this pathway to be repeated and amplified 2X106 molecules can be generated in 5 minutes
  • 24. C5 activation complex When an additional C3b binds to the C3 activation complex it converts it into a C5 activation complex. The C5 activation complex cleaves C5 into C5a and C5b. C5b begins the production of the MAC.
  • 26. Your attitude not your aptitude will determine your altitude. Aamir Ali Khan