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Chapter
4
Complement
systemComplement(C):
agroup
ofglobulins
that
exist
inthe
serum
of
normal
humanor
animal
,relate
to
immune
response
andbear
of
enzyme
activity
after
beingactivated.Jules
Bodet
(1870-1961),Discoverer
of
complementPart
I
IntroductionComponent
of
Complement
and
definition1.Connatural
components
of
the
complements:components
which
take
part
in
the
activation
ofcomplementsclassical
pathway:
C1-C9,
C1----C1q,C1r,C1s-------components
.C5,C6,C7,C8,C9---------
terminal
pathwayalternative
pathway:
B,
D,
factorMBL
pathway:mannan-binding
lectin(甘露糖结合凝集素,MBL),serine
proteinase.regulatory
factors
existed
on
cells
or
in
humproperdin(备解素),C1
inhibitor
(
C1抑制物,ClINH),I
factor,C4
binding
protein
(C4结合蛋白,C4BP),S-protein、SP40/40、membrane
cofactor
protein(膜辅助因子蛋白,MCP)、decay
accelerating
factor(衰变加速因子,DAF)、homologousrestriction
factor(同源限制因子,HRF),membrane
inhibtor
of
reactive
lysis(膜反应性溶解抑制物,MIRL)The
complement
receptor
:
CR1,
CR2,
CR3,
CR4,CR5II.
Denomination
of
complentsclassical
pathway
components:
according
to
tfinding
time
:C1—C9Other
connatural
components
:
D
factor
,Bfactor,
etc.Regulatory
proteins:
according
to
it’s
funFragments:
“a”
small
fragments
and
“b”for
big
fragmentsactivated
components:C16.inactivated
components:
iC1III.
The
physical
and
chemical
featuresof
complementsThe
concentration
of
C
in
serum
is
stable
,
C3
highest
in
all
of
complement
components:1.20-
1.60g/LThe
liver
is
an
important
organ
producingcomplenment.Sensitive
to
heat
:
inactivated
by
heating
infor
30
minPart
II
The
activation
of
complementsystem1.Three
pathway
:classical
pathway
:from
C1
By
Ag-Abalternative
pathway:
from
C3
By
the
surfacemicrobeMBL(lectin
)pathway:
from
C4
and
C2
byMBL2.Terminal
pathway
:
same
in
the
3
pathwayI.
classical
pathwayActivator:
The
C1
molecule
binds
to
theantibody
attached
to
the
surface
of
antigen
ttrigger
the
classical
pathwayComponents:
C1---C9Process:
C1--C4,C2—C3,4,5,6,7,8,9phase
of
recognition:
recognizing
unit(C1qrs)Phase
of
activation:
activatingunit(
C4,C2,C3)Phase
of
attack:
membrane-attack
complex(MAC)1.
Phase
of
recognition:
C
1C1q
binds
to
complement-binding
site
of
AbThe
C1q
molecule
has
six
globular
heads
joineda
common
stem
by
long
filamentous
domains
.
Eachglobular
head
can
bind
to
one
Fc
domain
and
bindiof
two
or
more
globulin
heads
activates
the
C1qmoleculeFabfragmentFcfragmentExploredC1qcombingsiteConformation
of
IgC1qcombingsite
wascoveredBefore
combining
withAgAfter
combining
withAgCH1CH2Each
of
C1should
bindto
more
than
2
com-plement
binding
sitesIg
before
activationOnly
the
immuno-complex
formed
byIgG1-3
and
IgM
canactive
C1The
free
Ig
can’tactivate
C11、phase
of
activationPhase
of
recognitionFormation
of
C3
convertaseC3
convertase2.
Phase
of
activation:
generate
C3convertase
and
C5
convertaseC1
activate
C4
and
C2Phase
of
activation
-1:formation
of
C3
convertaseC3
convertase
and
C3Opsonization
of
ComplementPhase
of
activation
–2:formation
of
C5
convertaseC5
convertasePhase
of
activation
–2:formation
of
C5
convertase3.phase
of
attack(terminal
pathway)formation
of
MACmembrane-attack
complex(MAC)generate
the
MAC----C56789cytolysisClassical
pathwayIgM/IgG
–Ag
complexC4C4b
+C2C4aC2aC3C3bC3aMg++C1q
:
r
:
sCa++
Ca++C4b2b
(C3convertase)C4b2b3b(C5convertase)II.
alternative
pathway
:The
initiating
substances:some
components
of
bacteria
wallAggregated
IgA
or
IgG4-----------providing
a
surface
for
Complement
bComponents
and
process:C3,4,5,6,7,8,9Function:
spontaneous
reaction
towards
microbeThere
is
a
spontaneous
conversion
of
C3
toC3b.
Ordinarily
the
C3b
is
quicklyinactivated:
the
C3b
binds
to
inhibitoryproteins,
and
the
process
is
aborted.I(Inhibitory)factorBFactor
DSpontaneous
conversion
of
C3C3C3aC3bC3bBbP——C3转化酶(C3
convertase)C3bnBb——C5转化酶(C5
convertase)Spontaneousconversion
orfrom
classicalpathwayC3bB
factorD
factorC3bBbC3bBbC3
convertaseC3C3bC3bnBbC5
convertaseenlargeC3bC3bBC3positive
feedback
loop
of
C3DfactorC3bBbBfactorIn
alternative
pathway,
Complement
canrecognize
self
from
nonselfalternative
pathway
is
the
important
enlarmechanism
of
ComplementIII.
MBL
pathwayManose-binding
lectin(MBL)Manose-binding
protein(MBP):
acute
phase
proteinproduced
by
liverCombine
with
manose
on
thesurface
of
microbeInitiating
substances:
MBL
combine
withmanose
on
the
surface
of
microbe
,thenoperate
with
MASP(MBL-associated
serineprotease)Process:MBL-manose-MASP----C4,2-C3,5,6,7,8,9mannanMBPmannanMBPMASPC4C4a
+
C4bC2C2a
+
C2bC4b2b(C3convertase)+
MASPIV.
Terminal
pathway—generate
MACC5b+C6+C7+C8+C9
=
MACsMACMACs造成的细胞膜损伤C6
C7C8C5bC9多聚体补
体杀
伤
寄
生
虫Effect
of
MACV.
comparation
of
there
pathwaysMBL-manoseMASPPart
III. regulation
of
Complement
systemThe
explosive
potential
of
the
complementsystem
requires
that
it
be
kept
under
tightcontrol.
At
least
12
proteins
are
known
thatdo
this.Mechanism
of
C
regulationregulation
of
self-inactive
:decayactivation
of
regulatory
factorsFactor
H
removes
Bb
from
the
alternativepathway
C3
convertase
breaking
thepositive
feedback
loop.Factor
I
inactivates
C3b
and
C4b.C1
inhibitor
(C1INH)
binds
to
sites
onactivated
C1r
and
C1s
shutting
down
theirproteolytic
activity.Regulation
of
classic
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