16.8
Complement

Explain
the
role
of
complement
in
innate
immunity.


a)  What
are
the
three
effects
on
microbes
by

    co...
Role
of
Complement
System
in

                Immunity

•  Complement
system
is
made
up
of
over
30
proteins

   synthesize...
The
Common
Pathway

•  Step
1
–
acAvate
C3,
promotes
opsonizaAon

   and
phagocytosis

•  Step
2
–
acAvate
C5,
promotes
in...
Step
1:
Ac*vate
C3

•  C3
is
split
into
C3a
and


  
C3b,
catalyzed
by
C3


  
convertase

•  C3b
binds
to
surface
to


  ...
Step
2:
Ac*vate
C5




•  C3b
acts
as
the
C5
convertase,


  
spliWng
C5

into
C5a
and
C5b

•  C5a
promotes
inflammaAon
by
...
Step
3:
Forma*on
of
the

    Membrane
A:ack

         Complex

•  C5b
binds
to
the
surface

   of
the
bacterial
cell

•  C...
3
Ways
to
AcAvate
Complement

•  Classical
pathway
–
anAbodies
(part
of

   acquired
immunity)

•  AlternaAve
pathway
–
a[...
The
Classical
Pathway:

  adapAve
immunity

•  A
specific
anAbody

   recognizes
and
binds
to
a

   bacterial
cell

•  C1
b...
AnAbodies
&
AnAgens

•  AnAbodies
are
proteins
produced
by
B
cells

•  Part
of
our
acquired
immunity

•  AnAbodies
bind
to...
The
AlternaAve
Pathway:

    innate
immunity

•  Complement
proteins
B,
D
&

   F
circulate
throughout
the

   body

•  Bi...
The
LecAn
Pathway:

  innate
immunity

•  LecAn
is
a
protein
that

   recognizes
and
binds
to

   bacterial
carbohydrates
...
Evading
Complement

•  Capsule

   –  The
capsule
is
a
coaAng
surrounding
the
cell
wall

   –  One
component
of
the
capsul...
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Chapter 16 Obj 08

  1. 1. 16.8
Complement
 Explain
the
role
of
complement
in
innate
immunity.

 a)  What
are
the
three
effects
on
microbes
by
 complement?
 b)  What
is
the
common
pathway/cascade
of
complement?

 c)  What
are
the
three
pathways
of
acAvaAng
 complement?

 d)  What
is
an
anAgen?
 e)  What
is
an
anAbody?
 f)  What
is
a
lecAn?
 g)  What
are
2
ways
bacteria
might
evade
complement?

  2. 2. Role
of
Complement
System
in
 Immunity
 •  Complement
system
is
made
up
of
over
30
proteins
 synthesized
by
the
liver,
circulate
in
the
blood
 •  Many
complement
proteins
are
inacAve
and
must
be
 acAvated.
 •  AcAvated
complement
acts
in
a
cascade
that
causes

 1.  inflammaAon:
dilaAon
of
arterioles,
release
of
 histamine
&
increased
permeability
of
capillaries
 2.  opsonizaAon:
protein
binds
to
microbe
making
it
 easier
to
phagocyAze
 3.  cytolysis:
a
complex
of
several
proteins
can
form
 holes
in
microbe
membranes
causing
leakiness
and
 cell
rupture

  3. 3. The
Common
Pathway
 •  Step
1
–
acAvate
C3,
promotes
opsonizaAon
 and
phagocytosis
 •  Step
2
–
acAvate
C5,
promotes
inflammaAon
 •  Step
3
–
form
MAC,
promotes
cytolysis

  4. 4. Step
1:
Ac*vate
C3
 •  C3
is
split
into
C3a
and

 
C3b,
catalyzed
by
C3

 
convertase
 •  C3b
binds
to
surface
to

 
enhance
phagocytosis
(opsonizaAon)
 •  C3b
is
also
an
enzyme
that
catalyzes
the
next
step
 •  C3a
promotes
inflammaAon
by
sAmulaAng
mast
 cells
to
release
histamine


  5. 5. Step
2:
Ac*vate
C5
 •  C3b
acts
as
the
C5
convertase,

 
spliWng
C5

into
C5a
and
C5b
 •  C5a
promotes
inflammaAon
by

 
sAmulaAng
mast
cells
to
release
histamine
(along
 with
C3a)
 •  C5b
is
begins
the
chain
reacAon
of
proteins
 binding
to
the
surface
of
a
microbe

  6. 6. Step
3:
Forma*on
of
the
 Membrane
A:ack
 Complex
 •  C5b
binds
to
the
surface
 of
the
bacterial
cell
 •  C6,
then
C7
and
C8
bind
 in
sequence
 •  These
4
proteins
a[ract
 or
recruit
C9
to
bind
 •  Several
C9
proteins
bind
 in
a
pa[ern
to
form
a
 huge
pore
puncturing
 the
plasma
membrane
 and
allowing
bacterial
 cytoplasm
to
leak
out
‐
 cytolysis


  7. 7. 3
Ways
to
AcAvate
Complement
 •  Classical
pathway
–
anAbodies
(part
of
 acquired
immunity)
 •  AlternaAve
pathway
–
a[racAon
of
 complement
proteins
to
microbial
cell
walls
 •  LecAn
pathway
–
proteins
that
bind
to
 bacterial
carbohydrates

  8. 8. The
Classical
Pathway:
 adapAve
immunity
 •  A
specific
anAbody
 recognizes
and
binds
to
a
 bacterial
cell
 •  C1
binds
to
the
anAbodies
 –  The
interacAon
acAvates
 enzymaAc
funcAon
of
C1
 •  AcAve
C1
a[racts
and
clips
 C2
and
C4
into
C2a,
C2b,
C4a
 &
C4b
 •  C2a
combines
with
C4b
to
 form
an
acAve
C3
convertase

  9. 9. AnAbodies
&
AnAgens
 •  AnAbodies
are
proteins
produced
by
B
cells
 •  Part
of
our
acquired
immunity
 •  AnAbodies
bind
to
small
pieces
of
microbes,
 called
anAgens,
to
iniAate
a
variety
of
immune
 responses
 •  AnAgens
are
substances
that
sAmulate
the
 producAon
of
anAbodies…anAbody
generators
 •  The
classical
pathway
is
iniAated
when
an
 anAbody
binds
to
its
anAgen

  10. 10. The
AlternaAve
Pathway:
 innate
immunity
 •  Complement
proteins
B,
D
&
 F
circulate
throughout
the
 body
 •  Bind
to
microbial
cell
wall
 components
(glycolipids)
 •  B,
D
&
F
a[ract
C3
and
act
as
 a
C3
convertase

  11. 11. The
LecAn
Pathway:
 innate
immunity
 •  LecAn
is
a
protein
that
 recognizes
and
binds
to
 bacterial
carbohydrates
 •  LecAn
a[racts
C2
&
C4
and
 catalyzes
the
spliWng
of
 both
proteins
into
C2a,
 C2b,
C4a
&
C4b
 •  C2a
combines
with
C4b
to
 form
an
acAve
C3
 convertase

  12. 12. Evading
Complement
 •  Capsule
 –  The
capsule
is
a
coaAng
surrounding
the
cell
wall
 –  One
component
of
the
capsule
is
sialic
acid
which
can
 prevent
opsonizaAon
(too
slippery
for
C3b)
 –  Another
component
present
for
some
bacteria
is
O
 polysaccharide
which
blocks
binding
of
the
MAC
 complex
(C5b,
C6,
C7,
C8,
C9)
 •  Secreted
enzymes
 –  Some
bacteria
secrete
C5a
pepAdase,
which
destroys
 C5a
–
impair
inflammaAon
and
recruitment
of
 phagocytes

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