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Complement System

The complement system is a group of proteins that mediate various functions including opsonization, membrane attack, and inflammation. It consists of three activation pathways - classical, lectin, and alternative - that are tightly regulated to prevent damage to host cells. Laboratory tests are used to identify deficiencies in the complement system that may underlie recurrent or severe infections.

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El Fatih
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155 views

Complement System

The complement system is a group of proteins that mediate various functions including opsonization, membrane attack, and inflammation. It consists of three activation pathways - classical, lectin, and alternative - that are tightly regulated to prevent damage to host cells. Laboratory tests are used to identify deficiencies in the complement system that may underlie recurrent or severe infections.

Uploaded by

El Fatih
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© © All Rights Reserved
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
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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

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