Transcript Complement system

Effector mechanisms of
humoral immunity
The Complement System
(C’)
Activation pathways
Effector functions
Regulation of complement activation
Complement system
(complements i.e. assists functions of antibody)
Jules Bordet
(1870-1961)
1919.
Nobel prize
For complement-mediated
bacteriolysis
Complement system
Consists of serum and cell surface proteins
involved in defense against pathogens and
tissue damage mediated by antibodies
Effector mechanism of both innate and
adaptive humoral immunity
Complement system
Over 30 serum and cell surface proteins:
- Complement components
(in serum inactive, activated sequentially as a cascade)
- Complement receptors
(cell surface, recognize activated components)
- Regulatory proteins of complement
(both in serum and cell surface, inhibit activated components)
Complement system
Pathways of activation
- Classical
- Alternative
- Lectin
Activation and
functions of
complement
(overview)
Activation
pathway
Early steps
Classical
C1, C4, C2
C3, C5, C6, C7, C8, C9
Lectin
MBL, C4, C2
C3, C5, C6, C7, C8, C9
Alternatve
C3, B, D (P)
C3, C5, C6, C7, C8, C9
Late steps
a
Ag-Ab complex
(microorganism and IgG or IgM Ab)
Classical
Lectin
C1
b
C4
C2
MBL
C3 convertase
microorganism
D
B
Alternatve
C5 convertase
C3
Effector functions
(elimination of pathogen)
microorganism
Early steps
Late steps
Early steps
of
complement
activation
B
D
MASP
P
MBL
Late steps of complement activation
C6 C7 C8 C9
MEMBRANE
ATTACK
COMPLEX
C5-C9
MAC
C5a C5b
IgG
Lysis
Bacterium
IgM
C5
Activated
C1
C3 CONVERTASE
C4b2b3b
C4b2b
C5 CONVERTASE
C3
C3b C3a
C4
C4a
C1
C2
C4b C2b
C2a
C6 C7 C8 C9
MEMBRANE
ATTACK
COMPLEX
Lysis
C5-C9
MAC
C5a C5b
Bacterium
C5
MBL
MASP
C3 CONVERTASE
C4b2b3b
C4b2b
C5 CONVERTASE
C3
C3b C3a
C4
C4a
C2
C4b C2b
C2a
C3a
C3b
C3
Ba
C3
C3b
Alternative C5
convertase
Bb
C3bB
C3bBb
C3bBb3b
Alternative C3
convertase
Factor B
Bacterium
Factor D
Properdin
Lysis
C5-C9
MAC
C5b
C5a
MEMBRANE
ATTACK
COMPLEX
C9
C8
C7
C6
C5
Effector functions of activated complement
- Cytolysis (MAC)
Cytolysis (MAC)
Effector functions of activated complement
- Cytolysis (MAC)
- Opsonization (C3b, C4b)
Opsonization and phagocytosis
(C3b, C4b)
Effector functions of activated complement
- Cytolysis (MAC)
- Opsonization (C3b, C4b)
- Stimulation of inflammation (C5a, C3a, C4a)
Stimulation of inflammatory rections
(C5a, C3a, C4a)
Activation of mast cells and neutrophils
(anaphylatoxins)
Effector functions of activated complement
- Cytolysis (MAC)
- Opsonization (C3b, C4b)
- Stimulation of inflammation (C5a, C3a, C4a)
- Stimulation of humoral response (C3d)
Stimulation of humoral
immunity (B cells)
Effector functions of activated complement
- Cytolysis (MAC)
- Opsonization (C3b, C4b)
- Stimulation of inflammation (C5a, C3a, C4a)
- Stimulation of humoral response (C3d)
- Immune complex clearance (C3b)
Immune complex clearance (C3b)
Immune complex clearance (C3b)
Regulatory proteins of complement
Regulatory proteins of complement
Complement system
(animation)
http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_1.html
Laboratory tests for complement
assesment
Quantification of compoments
(C3, C4, MBL - RID, nephelometry)
- concentration: g/L (mg/ml)
Functional tests
for classical and alternative pathway of
activation
1. Activation of complement system is
a. mannose binding lectin (MBL)
2. Complement activation pathways are
b. effector mechanism of innate and
adaptive immunity
c. factor B, factor D, properdin
3. Central role in complement activation belongs
to
4. First component in lectin pathway is
d. classical, alternative and lectin
5. Activators of classical pathway are
e. C1, C4, C2
6. Components of alternative pathway are
f. IgM and IgG bound to antigen
7. Proteins involved in early steps of classical
pathway are
g. C3 component
8. Important opsonin is
h. MAC
9. Inflammatory reactions are induced by
i. C3b
10. Osmotic lysis of microbes are mediated by
j. C3a, C4a and C5a
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b 2._____
d
g
a
f
c
e
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i
9.____
j
10.____
h