Complement System 2024381238400

COMPLEMENT SYSTEM
Dr. Animesh
Associate Professor
28/02/2024
Learning objectives
Definitions
Classical, alternate and lectin pathway
Role of complement
Complement deficiencies
COMPLEMENT
• Represents:
A group of proteins normally found in serum
In inactive form
Augment the immune responses when activated
• Constitute about 5% of normal serum proteins
• Their level does not increase following infection or

vaccination
COMPLEMENT SYSTEM
• Complement system comprises of about 30

serum proteins grouped into:
Complement components
Properdin system
Regulatory proteins
NOMENCLATURE OF COMPLEMENTS
• Complement components are named by numerals
• There are nine components: C1 to C9
• C1 has three subunits: C1q, C1r and C1s
• Properdin system and the regulatory proteins are

named by letter symbols, e.g., Factor-B
SYNTHESIS OF COMPLEMENT
• Liver: Major site of synthesis of complement proteins
• Minor sites include:

Blood monocytes
Tissue macrophages
Epithelial cells of GIT and genitourinary tract

COMPLEMENT ACTIVATION
• All complement proteins are synthesized in inactive
form (zymogens)
• Activated by proteolysis
• Have two unequal fragments (large & small)
Larger fragment: Usually designated as ‘b’ (e.g. C3b)
Smaller fragment: Designated as ‘a’ (e.g. C3a)
An exception is C2a which is larger fragment

• During proteolysis, smaller fragment is removed
exposing the active site on the larger fragment
• The larger fragment participates in the cascade

reaction of complement pathway
• The smaller fragment diffuses away to mediate

other functions
CASCADE REACTION
Fragments of complements interact in a definite

sequential manner with a cascade like effect, which
leads to formation of complex
Such complex having enzymatic activity is

designated by putting a bar over the number or
symbol (e.g. C 3bBb)
COMPLEMENT PATHWAYS
1. Classical pathway:
 Antibody dependent pathway
 Triggered by the antigen antibody complex formation
2. Alternative pathway:
 Antibody independent pathway
 Triggered by the antigen directly
3. Lectin pathway:
 Recently described pathway
 Resembles classical pathway but antibody independent
STAGES OF COMPLEMENT ACTIVATION
• There are four stages in the activation of any of
the complement pathways
Initiation of the pathway

Different in all the 3
pathways
Formation of C3 convertase
Formation of C5 convertase
Identical in all the 3
Formation of MAC pathways
(Membrane Attack Complex)
Features Classical pathway Alternative pathway Lectin pathway
Activator (initiator) Antigen antibody Endotoxin Carbohydrate

complex IgA, IgD, Cobra residue of bacterial
venom, Nephritic cell wall (mannose
factor binding protein) that
binds to host lectin
antigen.
First complement C1 C3b C4

activated
C3 convertase C14b2a C3bBb MBL/MASP-C4b2a
C5 convertase C14b2a3b C3bBb3b MBL/MASP-

(C3 convertase + 3b) C4b2a3b
Complement level All C1-C9: Low C1,C4,C2- Normal C1- Normal

in the serum Others- Low Others- Low
Immunity Acquired Innate Innate

The Functions of Complement
1. Lysis of cells, bacteria, and viruses – the major effector
of the humoral branch of the immune system
2. Opsonization, which promotes phagocytosis of
particulate Ags
3. Binding to specific complement receptors on cells of
the immune system, triggering specific cell functions,
inflammation, and secretion of immunoregulatory
molecules
4. Immune clearance, which removes immune complexes
from the circulation and deposits them in the spleen
and liver
COMPLEMENT DEFICIENCIES
Complement Pathway(s) involved Disease/pathology
protein
deficiencies
C1, C2, C3, C4 C1,C2,C4-Classical pathway SLE,

Glomerulonephritis,
C3- Common deficiency Pyogenic infections
Properdin, Factor Alternative pathway Neisseria and pyogenic

D infection
Membrane attack Common deficiency Disseminated Neisseria

complex (C5-C9) infection
C1 esterase inhibitor Overactive classical pathway Hereditary angioneurotic

edema
N K
H A
T OU
Y

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COMPLEMENT SYSTEM

Classical, alternate and lectin pathway

In inactive form

Augment the immune responses when activated

• Constitute about 5% of normal serum proteins

• Their level does not increase following infection or

• Complement system comprises of about 30

• Complement components are named by numerals

• There are nine components: C1 to C9

• C1 has three subunits: C1q, C1r and C1s

• Properdin system and the regulatory proteins are

• Liver: Major site of synthesis of complement proteins

• Minor sites include:

Epithelial cells of GIT and genitourinary tract

• Have two unequal fragments (large & small)

Larger fragment: Usually designated as ‘b’ (e.g. C3b)

Smaller fragment: Designated as ‘a’ (e.g. C3a)

An exception is C2a which is larger fragment

• The larger fragment participates in the cascade

• The smaller fragment diffuses away to mediate

Fragments of complements interact in a definite

Such complex having enzymatic activity is

Initiation of the pathway

Activator (initiator) Antigen antibody Endotoxin Carbohydrate

First complement C1 C3b C4

C5 convertase C14b2a3b C3bBb3b MBL/MASP-

Complement level All C1-C9: Low C1,C4,C2- Normal C1- Normal

Immunity Acquired Innate Innate

C1, C2, C3, C4 C1,C2,C4-Classical pathway SLE,

Properdin, Factor Alternative pathway Neisseria and pyogenic

Membrane attack Common deficiency Disseminated Neisseria

C1 esterase inhibitor Overactive classical pathway Hereditary angioneurotic

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