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The Complement System

The complement system is a defensive system consisting of over 30 proteins produced by the liver and found in circulating blood serum. It kills microbes in three ways: opsonization, inflammation, and cytolysis. The complement works as a cascade system where one reaction triggers another exponentially. There are two pathways - the classical pathway activated by antibodies, and the alternative pathway which does not require antibodies. Both pathways result in the formation of the membrane attack complex that causes cell lysis.

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Sai Kiran
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325 views27 pages

The Complement System

The complement system is a defensive system consisting of over 30 proteins produced by the liver and found in circulating blood serum. It kills microbes in three ways: opsonization, inflammation, and cytolysis. The complement works as a cascade system where one reaction triggers another exponentially. There are two pathways - the classical pathway activated by antibodies, and the alternative pathway which does not require antibodies. Both pathways result in the formation of the membrane attack complex that causes cell lysis.

Uploaded by

Sai Kiran
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 PPT, PDF, TXT or read online on Scribd
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THE COMPLEMENT SYSTEM

By,

Jyothindra Sai Kiran Kala


313106206008

THE
COMPLEME
NT 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.
Opsonins

eria
Bact

C3A

C3a increases the inflammatory response by


binding to mast cells and causing them to
release histamine

BUILDING THE C5
ACTIVATION COMPLEX
Eventially 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
C5activation 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 C9s
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

Animation

athaway

of the classical p

OVERVIEW

THE ALTERNATIVE PATHWAY

The alternative pathway is part of the nonspecific defense because it does not need
antibodies to initiate the pathway.
The alternative pathway is slower than the
Classical pathway

THE ALTERNATIVE
COMPLEMENT
PATHWAY

INITIATION OF THE ALTERNATIVE


PATHWAY
C3 contains in unstable
thioester bond.
This unstable bond
makesC3 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

THANK YOU

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