Sistem Komplemen NFK

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SISTEM KOMPLEMEN

Neng Fisheri KurniatiFarmakologi-Farmasi KlinikSekolah Farmasi - ITB

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THE NEXT ???

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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

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antibodies "finger" the target,

complement destroys it

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Sistem Komplemen

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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

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Pendahuluan

Present normally among the plasma proteins

in blood as well as among the proteins thatleak out of the capillaries into the tissuespaces

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Important Effects of Complement

System Opsonization and phagocytosis

Lysis

Neutralization Agglutination of viruses

Chemotaxis

Activation of mast cells and basophils Inflammatory effects

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Opsonization

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Membrane attack complex or Lytic

complex

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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

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Sistem komplemen terbagi 2

1. Jalur klasik (classical pathway)

2. Jalur alternatif (alternative pathway)

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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

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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

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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

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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

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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

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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

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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

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Alternative Pathway

Tidak memerlukan interaksi spesifik denganantigen untuk menimbulkan aktivasi

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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

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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

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Alternative Pathway

ATTACK

C5 is cleaved to C5a and C5b

C5b then starts the assembly of the MembraneAttack Complex

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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

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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

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Summary - Function

OpsonizationC3b

ChemotaxisC5a (attracts neutrophils)

Increases vasodilation & permeabilityofcapillary beds via mast cell and basophilactivation C3a & C5a (Anaphylatoxins)

Cellular Lysisvia the MAC

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Apa yang akan terjadi ketika kita

kekurangan protein yang terlibat

dalam sistem komplemen?

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Antigen presenting Cell

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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

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