Complement

•Synthesis and attachment of specific antibody to invading

microorganisms does not directly lead to destruction.
 
•It is a "label" that identifies them as targets for destruction.
 
•Microorganisms coated with IgG antibody are more susceptible
to phagocytosis by neutrophils and macrophages.
 
•Complement consists of a series of blood proteins, which when
activated, lead to lysis of target cells.
Three Major Biological Activities of Complement
macrophage target cell

Activation Cytolysis

Complement

Opsonization
Bacteria

Phagocytic cell
 The Complement System
•Complement is the term applied to a plasma effector system:
--direct mediation of acute inflammatory reactions
--destruction of many kinds of cells, bacteria and viruses.

•Complement factors has some hormone-like properties:

 
--recruit other humoral and cellular effectors;
 
--induces directed neutrophil migration;
 
--triggers histamine release from mast cells;
 
--stimulates release of lysosomal enzymes from PMN's.
 Complement Pathway(s)
Antigen-antibody complex Bacteria, yeast, virus, or tumor cell
C1q-C1r-C1s C3

recognition unit (C1q-C1r-C1s) B

C4 D Alternative
activation unit (C4, C2, C3)
Classical C2 properdin Pathway
Pathway C3
C3b, opsonin, substance that
“binds” to surface of target cell
C5
Assembly of the C5a, anaphylatoxin, act as mediator
C6, C7, C8
Terminal of local inflammatory response
Components C9 membrane attack (C5-C9)
Perforates cell membrane of
target cell
 “Membrane Attack Complex” (MAC) of Complement

Membrane Attack Complex

Glycocalyx

Lipid bilayer

Transmembrane channel Transmembrane channel

Micelle
A Different “View” of Complement Activation

Ag/Ab C3 M’organisms
Complex

Classical Alternative
Pathway Pathway
(Acquired) (Innate)

C3b Opsonizing (“coating”)

C5 - C9 Terminal Sequence
 Opsonization by C3b
•C3b coatings of cells: Opsonin
  binding
FcR Ab
--facilitate adherence of bacteria,

Y
viruses and other m'organisms to PMN +
neutrophils, monocytes and
macrophages;
 
--facilitate ingestion of certain
bacteria by neutrophils and monocytes; PMN ++
 
--aids ingestion by activated C3b
CR3
macrophages;
  FcR
Ab

Y
--facilitates IgG-induced phagocytosis PMN
and cell cytotoxicity. +++

CR3 C3b
 “Actions” of Complement

C3a and C5a

MAC
(C5-C9)

C5a
C3b
 Activating Stimuli
Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-
Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane
(tissue injury)

Bacterial lysis Phagocytosis Chemotaxis Vasodilation

Permeability
 Activating Stimuli
Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-
Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane
(tissue injury)
Complement Activation
Alternate Pathway

C3 and C5

C3b and C5b

Membrane attack
complex

Bacterial lysis Phagocytosis Chemotaxis Vasodilation

Permeability
 Activating Stimuli
Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-
Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane
(tissue injury)
Complement Activation
Complement Activation
Alternate Pathway
Classical Pathway

C3 and C5
C3b and C5b C3b

Membrane attack Opsonization

complex

Bacterial lysis Phagocytosis Chemotaxis Vasodilation

Permeability
 Activating Stimuli
Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-
Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane
(tissue injury)
Complement Activation
Complement Activation
Alternate Pathway
Classical Pathway

C3 and C5
C3b and C5b C3b C3a
C5a
Membrane attack Opsonization (Anaphalytoxins)
complex

Bacterial lysis Phagocytosis Chemotaxis Vasodilation

Permeability
 Activating Stimuli
Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-
Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane
(tissue injury)
Complement Activation
Complement Activation Mast cell
Alternate Pathway degranulation
Classical Pathway

C3 and C5
Histamine
C3b and C5b release
C3b C3a
Membrane attack C5a
Opsonization (Anaphalytoxins)
complex

Bacterial lysis Phagocytosis Chemotaxis Vasodilation

Permeability
 Activating Stimuli
Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-
Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane
(tissue injury)
Complement Activation Mast cell
Complement Activation
Alternate Pathway degranulation
Classical Pathway

C3 and C5
Histamine
C3b and C5b release
C3b C3a
Membrane attack C5b
Opsonization (Anaphalytoxins)
complex

Bacterial lysis Phagocytosis Chemotaxis Vasodilation

Permeability
 Activating Stimuli
Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-
Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane
(tissue injury)
Complement Activation Mast cell
Complement Activation
Alternate Pathway degranulation
Classical Pathway Hageman factor

C3 and C5
Histamine Coagulation Kallikrein
C3b and C5b release cascade Activation
C3b C3a
Membrane attack C5b Bradykinin
Opsonization (Anaphalytoxins)
complex

Bacterial lysis Phagocytosis Chemotaxis Vasodilation

Permeability
 Animations
• Complement Animations & Online Quiz
• Complement Animations & Quiz