COMPLEMENT SYSTEM
DEWI WULANDARI
Clinical Pathology Departement
Faculty of Medicine, University of Indonesia
Cipto Mangunkusumo Hospital
Jakarta
Complement system
• First described in the 1880s as a system
capable of inducing lysis of bacteria and red
cells.
• In 1919, the Nobel Prize:
the Belgian microbiologist Bordet for his description
of the complement system.
• The term complement was given to
– the unnamed protein in serum from guinea pigs
– that complemented the antibody fraction in a lytic
assay.
• Today, the complement system is understood
as:
– a group of 14 proteins (C1-9, Factor B, D, H, I,
properdin)
– comprising the complement cascade
– more than 10 regulatory proteins
– at least seven receptors
– mediate the biologic functions
– a variety of proteins are capable of activating the
cascade.
Synthesis & Function
• Normal: 5% of serum protein
• In inflammation states: 7%
• Synthesis :
– Hepatocytes
– C1q, properdin, C7 : by myeloid cells
– Factor D : by adipocytes
• Main Biologic functions:
– Opsonization
– Membrane pertubation including lysis
– Proinflammatory mediator
Activations
• Classical pathway
• Alternative pathway
• Lectin activation
pathways
Classical Pathway
• The first pathway to be described
& was thought as the only
complement activation
mechanism.
• Activated primarily by immune
complexes
• Only IgG and IgM can activate
complement.
IgM > IgG3 > IgG1 and IgG2
• Other activators:
C-reactive protein, serum amyloid
P, B-amyloid, DNA/chromatin,
cytoskeletal filaments, some
pathogens (mechanisms remain
unclear)
Alternative Pathway
• The basis for this pathway
is a spontaneous hydrolysis
of C3, which occurs in the
serum at a rate of 0.2% to
0.4% per hour.
• the alternative pathway is
generally activated through
the recognition of
oligosaccharide and charge
differences common to
pathogens.
The Lectin Activation Pathway
• The MBL (mannose-binding lectin)
protein is structurally related to C1q
• Part of the family, which includes
surfactant proteins and conglutin. H-
ficolin, L-ficolin, and M-ficolin
• MBL and ficolins all activate MBL-
associated serine proteases (MASPs)
to initiate the cascade.
The Lectin Activation Pathway
• Mammalian glycoproteins generally
are decorated with galactose and
sialic acid. that are not recognized by
MBL.
• MBL binds to oligosaccharides
associated with bacteria, yeast, and
parasites such as mannose, N-acetyl-
glucosamine, fucose, and glucose.
Membrane Attack Complex
• The cleavage of C5 followed
the bind of C6, C7, and C8
• can insert firmly into a lipid
membrane.
• The addition of C9 leads to the
formation of a true pore
• They are most efficient at
lysing gram-negative bacteria
and red blood cells., which
have no capability of repairing
membrane damage.
Complement in Inflammation
• Anaphylatoxin: C3a, C4a, C5a
• The receptors are expressed
on mast cells, basophils,
eosinophils, neutrophils,
platelets, endothelial cells,
and smooth muscle cells
• Activation may result as:
– Vasodilatation
– smooth muscle contraction
– Recruitment of neutrophils
– Aggregation of platelets
– Mucus release
– Macophages activation
Complement Receptors
Regulators
Regulators of the
classical pathway
Regulators of the
alternative pathway
Regulators of the MBL
activation pathway
Complement Deficiencies
Laboratory Tests
• Indications: Patient with
– recurrent sinopulmonary infections
– recurrent sepsis or systemic infetions
– Sepsis on a background of autoimmune disease
• Laboratory analysis:
– Quantitative: level of C1q, C3, C4 & other
components
– Qualitative: CH50, AH50
