Download COMPLEMENT activation - Akademik Ciamik 2010

Anna Tjandrawati
Clinical Pathology Department
Medical Faculty Padjadjaran University
Hasan sadikin General Hosptital Bandung
HOST DEFENSES IN INNATE IMMUNITY
Cells
Antigen presenting cells
Basophils
Eosinophils
Mast cells
Phagocytes
Humoral factors Complement proteins
Lactoferrin
Lysozyme
Pepsin
Stomach acidity
Anatomical barriers
Cilia
Mucus
Skin
Resident flora
Mainly nonpathogenic bacteria
COMPLEMENT
Definition :
a system comprised of a groups of plasma and cell
membrane proteins that play an important role in
host defense process.
Components:
 More than 30 proteins
 Synthesized in the liver, macrophages and
other cells
Functions :




Lysis of cells, bacteria, and viruses
Opsonization, which promotes phagocytosis of
particulate antigens.
Regulate inflammatory and immune responses
Regulate the biologic activity of cells.

CLASSICAL PATHWAY

ALTERNATIVE PATHWAY

MANNAN BINDING LECTIN PATHWAY
COMPLEMENT activation




As a cascade
Numerous protein of the complement system
are sequentially activated.
Activation typically refers to the conversion
zymogen to an enzymatic form
The enzymatic form cleave other complement
protein into two fragments
COMPLEMENT activation


Some fragments bind to receptors, while
others bind to microbial surfaces
One complement fragment associates with
intact protein to form cytocidal complexes that
insert into the membranes of cells ( bacteria)
resulting in bacteria destruction
C3 convertase
classical
pathway
C3 convertase
alternative
pathway
C5 convertase
classical
pathway
C5 convertase
alternative
pathway
Protein
Abbreviation
Regulatory Function
C1 inhibitor
C1 INH
Binds to C1, thereby preventing it
from initiating complement activation.
Properdin
Properdin
Stabilizes the alternative pathway C3
convertase
C4 binding protein
C4bp
Accelerates the dissociation of both
C3 convertases.
Decay accelerating factor
DAF
Accelerates the dissociation of both
C3 convertases.
Factor I (plus a cofactor)
Factor I
Cleaves and inactivates C3b and
C4b.
Anaphylatoxin inhibitor
AI
Proteolytically cleaves the
anaphylatoxins.
Membrane inhibitor of
reactive lysis.
MIRL of CD 59
Inhibits MAC formation
Homogenous restriction
factor
HRF
Inhibits MAC formation.
S-protein (also known as
Vitronectin)
S-protein
Inhibits MAC formation.
Receptor
Complement
Ligand
Cell Type for
Receptor
Receptor.-Ligand Interaction
Function
CR1
C3b and iC3b
Phagocytes
Erythrocyte
•Opsonin mediated recognition
of antigen
•Clearance of circulating
immune complex
CR2
iC3b
B lymphocytes
Mode of Epstein Barr virus
infection
CR3
iC3b
Phagocytes
Cellular adhesion
Opsonin mediated recognition
of antigen
CR4
iC3b
Phagocytes
Opsonin mediated recognition
of antigen
C3a/
C4a-R
C3a and C4a
Mast cell and basophils
Degranulation that leads to
release of histamine and other
inflammatory mediators
C5a-R
C5a
Mast cell and Basophils
Endothelial cells
Phagocytes
Degranulation that leads to
release of histamine and other
inflammatory mediators
Increase vascular permeability
Chemotaxis.
Biological activity of complement




Inflammatory response : C3a, C4a, C 5a
- Anaphylatoxins
- Chemokines/Chemotaxis
Phagocytosis: C3b
- Opsonin
Elimination of immune complex: C3b
- Opsonin and receptors
Osmotic lysis bacteria:C5b6789
- MAC(Membrane Attack Complex)
Deficiency
Disorder
C1 INH
Hereditary angioneurotic edema (HANE)
C2 and C4
Immune complex disorders  often
present in individual with systemic lupus
erythematosus (SLE)
C3
Pyogenic infections with encapsulated
bacteria
C5,6,7,8,9
Recurent infections with Neisseria spp.
GPI Linkages (DAF, Paroxysmal nocturnal hemoglobinuria
CD59)
Measurement of Overall Complement Activity
CH50 and AH50
Measurement of Complement Components

Radial Immunodiffusion (RID)

Nephelometry  rate nephelometry:
an assay in which the rate of immune complex
formation is measured