Upload
mawankurniawan17
View
249
Download
0
Embed Size (px)
Citation preview
7/26/2019 Sistem Komplemen NFK
1/37
SISTEM KOMPLEMEN
Neng Fisheri KurniatiFarmakologi-Farmasi KlinikSekolah Farmasi - ITB
7/26/2019 Sistem Komplemen NFK
2/37
THE NEXT ???
7/26/2019 Sistem Komplemen NFK
3/37
Keuntungan Interaksi antibodi-antigen :
1. coating virus atau bakteri sehingga
mencegah virus/bakteri berikatan ke selhost
2. Berikatan dengan toksin sehingga mencegahtoksin masuk ke sel
7/26/2019 Sistem Komplemen NFK
4/37
antibodies "finger" the target,
complement destroys it
7/26/2019 Sistem Komplemen NFK
5/37
7/26/2019 Sistem Komplemen NFK
6/37
Sistem Komplemen
7/26/2019 Sistem Komplemen NFK
7/37
7/26/2019 Sistem Komplemen NFK
8/37
Pendahuluan
Sistem komplemen merupakan bagian dari sistemimun dapatan.
It is named complement system because it wasfirst identified as a heat-labile component of serumthat complemented antibodies in the killing ofbacteria
It is now known that it consists of over30 proteinsand contributes3 g/Lto overall serum proteinquantities
7/26/2019 Sistem Komplemen NFK
9/37
Pendahuluan
Present normally among the plasma proteins
in blood as well as among the proteins thatleak out of the capillaries into the tissuespaces
7/26/2019 Sistem Komplemen NFK
10/37
Important Effects of Complement
System Opsonization and phagocytosis
Lysis
Neutralization Agglutination of viruses
Chemotaxis
Activation of mast cells and basophils Inflammatory effects
7/26/2019 Sistem Komplemen NFK
11/37
Opsonization
7/26/2019 Sistem Komplemen NFK
12/37
Membrane attack complex or Lytic
complex
7/26/2019 Sistem Komplemen NFK
13/37
7/26/2019 Sistem Komplemen NFK
14/37
Role of Macrophages in
activation process Macrophages present in tissues, phagocytose
and partially digest Ag and pass antigenicproducts by cell to cell contact directly tolymphocytes, leading to activation ofspecified lymphocytic clones
They also secrete Interleukin-1 which
promotes still further growth andreproduction of specific lymphocytes
7/26/2019 Sistem Komplemen NFK
15/37
Sistem komplemen terbagi 2
1. Jalur klasik (classical pathway)
2. Jalur alternatif (alternative pathway)
7/26/2019 Sistem Komplemen NFK
16/37
Classical Pathway
Diawali dengan ikatan antibodi dengan permukaan sel dandiakhiri dengan lisisnya sel
Protein yang terlibat = C1-C9 (urutan nomor berdasarkanwaktu ditemukannya, bukan urutan reaksi)
When complement is activated it is split into two parts a smaller of the two
B larger part and usually the active part (except with factor 2)
Remember 3 Key Words
ACTIVATION AMPLIFICATION
ATTACK
7/26/2019 Sistem Komplemen NFK
17/37
C1qC2C4
2a2b4b4
a
C3-convertase
C3
C3aC3b
C5-Convertase
C3abinds to receptors on
basophilsand mast cells
triggering them to release
there vasoactive compounds(enhances vasodilation and
vasopermeability) -
ANAPHYLATOXINC5
C5aC5b
C5ais a:
1. Potent anaphylatoxin
2. Chemoattractant for
neutrophils
C6
C7C8
C9
Classical
PathwayAndrew E Thompson MD FRCPC
Fellow in RheumatologyUniversity of British Columbia
7/26/2019 Sistem Komplemen NFK
18/37
Classical Pathway
ACTIVATION
C1qportion of C1 attaches to the Fc portion of anantibody
Only IgGand IgMcan activate complement
Once activated C1s is eventually cleaved whichactivates C4 and C2
C4b & C2a come together to form the C4b2awhich is
the C3 convertase
C3 convertase activates C3 to C3a and C3b
7/26/2019 Sistem Komplemen NFK
19/37
Classical Pathway
ACTIVATION
C3abinds to receptors on basophilsand mastcellstriggering them to release there vasoactive
compounds (enhances vasodilation andvasopermeability)
C3ais called an anaphylatoxin
C3b serves as an opsonin which facilitates immunecomplex clearance
7/26/2019 Sistem Komplemen NFK
20/37
Classical Pathway
AMPLIFICATION
Each C1s creates many C4b and C2b fragments
Each C4bC2a creates many C3b (activated C3)
Each C3b goes on to create many Membrane AttackComplexes
Example
1 C1S makes 100 C4bC2b 100 C4bC2b makes 10,000 C3b
10,000 C3b makes 1,000,000 MAC
7/26/2019 Sistem Komplemen NFK
21/37
Classical Pathway
ATTACK
Most C3b serves an opsonin function
Some C3b binds to C4bC2a to form the C5
convertase C4bC2aC3b C5 convertase cleaves C5 leading to the formation
of the Membrane attack Complex (C5-C6-C7-C8-C9)
The MAC punches holes in cell walls resulting inlysis
7/26/2019 Sistem Komplemen NFK
22/37
C1qC2C4
2a2b4b4
a
C3-convertase
C3
C3aC3b
C5-Convertase
C3abinds to receptors on
basophilsand mast cells
triggering them to release
there vasoactive compounds(enhances vasodilation and
vasopermeability) -
ANAPHYLATOXINC5
C5aC5b
C5ais a:
1. Potent anaphylatoxin
2. Chemoattractant for
neutrophils
C6
C7C8
C9
Classical
PathwayAndrew E Thompson MD FRCPC
Fellow in RheumatologyUniversity of British Columbia
7/26/2019 Sistem Komplemen NFK
23/37
Alternative Pathway
Tidak memerlukan interaksi spesifik denganantigen untuk menimbulkan aktivasi
7/26/2019 Sistem Komplemen NFK
24/37
Alternative Pathway
ACTIVATION
Spontaneous conversion from C3 to C3b occurs inbody
Normally, C3b is very short lived and quicklyinactivated by proteins on the surface of thebodys own cell walls
However, bacteria or other foreign material may
lack these surface proteins allowing C3b to bindand stay active
7/26/2019 Sistem Komplemen NFK
25/37
Alternative Pathway
AMPLIFICATION
Factor B binds to C3b
Factor B is then cleaved by factor D into Ba and Bb
C3bBb remains which acts as a C3 convertase (C3
C3a and C3b)
C3bBbC3b is formed which acts as a C5 convertase
7/26/2019 Sistem Komplemen NFK
26/37
Alternative Pathway
ATTACK
C5 is cleaved to C5a and C5b
C5b then starts the assembly of the MembraneAttack Complex
7/26/2019 Sistem Komplemen NFK
27/37
C3C3bC3a
Anaphylatoxin
B
D
Bb Ba
C3
C3a C3bC5-ConvertaseC3-Convertase
C5
C5aC5b
Alternative
Pathway
C6
C7
C8
C9
Andrew E Thompson MD FRCPC
Fellow in RheumatologyUniversity of British Columbia
7/26/2019 Sistem Komplemen NFK
28/37
Summary - Activation
Complement can be activated by the binding ofantibody (Classical) or by the adherance of C3b
to foreign material (Alternative)
The two pathways converge at the formation ofthe C5 convertase (C4b2a3b or C3bBbC3b)
The final common pathway is the formation of
the membrane attack complex
7/26/2019 Sistem Komplemen NFK
29/37
Summary - Function
OpsonizationC3b
ChemotaxisC5a (attracts neutrophils)
Increases vasodilation & permeabilityofcapillary beds via mast cell and basophilactivation C3a & C5a (Anaphylatoxins)
Cellular Lysisvia the MAC
7/26/2019 Sistem Komplemen NFK
30/37
7/26/2019 Sistem Komplemen NFK
31/37
7/26/2019 Sistem Komplemen NFK
32/37
Apa yang akan terjadi ketika kita
kekurangan protein yang terlibat
dalam sistem komplemen?
7/26/2019 Sistem Komplemen NFK
33/37
Antigen presenting Cell
7/26/2019 Sistem Komplemen NFK
34/37
Antigen Presenting Cell(APC)
Macrophages
B lymphocytes
Dendritic cells in spleen
and lymph nodes
Langerhanscells in skin
MHC I proteins present
antigen to cytotoxic Tcells
MHC II proteins presentantigen to helper T cells
7/26/2019 Sistem Komplemen NFK
35/37
7/26/2019 Sistem Komplemen NFK
36/37
7/26/2019 Sistem Komplemen NFK
37/37