CHAPTER SEVEN
Complement System
Introduction
The complement system is an essential part of the innate
immune system
It consists of plasma proteins that work together to fight
infections.
Plays a major role in innate immunity, but also supports
adaptive immunity.
Called “complement” because it complements the action of
antibodies and phagocytic cells.
First identified in the 1890s as a heat-sensitive substance and
named by Paul Ehrlich
Proteins circulate as inactive precursors (zymogens)
Activated in a cascade sequence, where one protein activates
another.
Definition
The complement system is a group of over 30 circulating and
membrane-bound proteins that interact in a regulated enzymatic
cascade to defend against microorganisms, promote inflammation,
enhance phagocytosis, and cause cell lysis.
Components of the Complement System
Complement proteins (C1–C9): Core plasma proteins that
form the complement cascade
o C1 complex → (C1q, C1r, C1s) → initiates classical
pathway
o C2, C4 → involved in classical & lectin pathways
o C3 → central and most important component
o C5–C9 → form the Membrane Attack Complex (MAC)
Regulatory proteins: Control and prevent excessive activation
(e.g., factors H, I)
Complement receptors: Found on immune cells to bind
complement fragments
Cell-bound proteins: Present on cell membranes and
participate in activation.
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, Activation of Complement System
Complement is activated in a sequential cascade, where each protein
activates the next one in the pathway. There are three main pathways of
activation:
1. Classical Pathway
The classical pathway involves complement proteins
It is triggered by by IgM and IgG antibodies, with IgM being
the most effective.
It begins with activation of C1 (C1q, C1r, C1s)
This leads to activation of C4 and C2, forming C3 convertase
(C4b2a)
Further activation results in C3 activation → C5 convertase →
Membrane Attack Complex (MAC).
Main Stages of Classical Pathway
1. Recognition Stage (C1 Complex)
Initiated by C1 (C1q, C1r, C1s)
C1q binds to the Fc region of antibodies (IgG or IgM)
Activates C1r and C1s enzymes
Begins the complement cascade
2. Activation Stage (C4, C2, C3)
C1s cleaves C4 → C4a + C4b
C4b binds to pathogen surface
C4b combines with C2a → C3 convertase (C4b2a)
C3 is cleaved into:
o C3a (inflammation)
o C3b (opsonization & amplification)
C3 is the central and most important complement protein
3. Formation of C5 Convertase
C3b joins C4b2a to form C5 convertase
Cleaves C5 into:
o C5a (strong inflammation)
o C5b (starts MAC formation)
4. Membrane Attack Complex (MAC)
C5b binds with C6, C7, C8, and C9
Forms pores in the pathogen membrane
Leads to cell lysis and destruction of microbes
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Complement System
Introduction
The complement system is an essential part of the innate
immune system
It consists of plasma proteins that work together to fight
infections.
Plays a major role in innate immunity, but also supports
adaptive immunity.
Called “complement” because it complements the action of
antibodies and phagocytic cells.
First identified in the 1890s as a heat-sensitive substance and
named by Paul Ehrlich
Proteins circulate as inactive precursors (zymogens)
Activated in a cascade sequence, where one protein activates
another.
Definition
The complement system is a group of over 30 circulating and
membrane-bound proteins that interact in a regulated enzymatic
cascade to defend against microorganisms, promote inflammation,
enhance phagocytosis, and cause cell lysis.
Components of the Complement System
Complement proteins (C1–C9): Core plasma proteins that
form the complement cascade
o C1 complex → (C1q, C1r, C1s) → initiates classical
pathway
o C2, C4 → involved in classical & lectin pathways
o C3 → central and most important component
o C5–C9 → form the Membrane Attack Complex (MAC)
Regulatory proteins: Control and prevent excessive activation
(e.g., factors H, I)
Complement receptors: Found on immune cells to bind
complement fragments
Cell-bound proteins: Present on cell membranes and
participate in activation.
Page 1 irep red bir Mire
, Activation of Complement System
Complement is activated in a sequential cascade, where each protein
activates the next one in the pathway. There are three main pathways of
activation:
1. Classical Pathway
The classical pathway involves complement proteins
It is triggered by by IgM and IgG antibodies, with IgM being
the most effective.
It begins with activation of C1 (C1q, C1r, C1s)
This leads to activation of C4 and C2, forming C3 convertase
(C4b2a)
Further activation results in C3 activation → C5 convertase →
Membrane Attack Complex (MAC).
Main Stages of Classical Pathway
1. Recognition Stage (C1 Complex)
Initiated by C1 (C1q, C1r, C1s)
C1q binds to the Fc region of antibodies (IgG or IgM)
Activates C1r and C1s enzymes
Begins the complement cascade
2. Activation Stage (C4, C2, C3)
C1s cleaves C4 → C4a + C4b
C4b binds to pathogen surface
C4b combines with C2a → C3 convertase (C4b2a)
C3 is cleaved into:
o C3a (inflammation)
o C3b (opsonization & amplification)
C3 is the central and most important complement protein
3. Formation of C5 Convertase
C3b joins C4b2a to form C5 convertase
Cleaves C5 into:
o C5a (strong inflammation)
o C5b (starts MAC formation)
4. Membrane Attack Complex (MAC)
C5b binds with C6, C7, C8, and C9
Forms pores in the pathogen membrane
Leads to cell lysis and destruction of microbes
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