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.

Activation

macrophage

Cytolysis

target cell

Opsonization

Bacteria

Phagocytic cell

Three Major Biological Activities of Complement

Complement

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)

C1q-C1r-C1s C3

B

C4 D

C2 properdin

C3

C5

C6, C7, C8

C9

Alternative PathwayClassical

Pathway

Assembly of theTerminal Components

Antigen-antibody complex

recognition unit (C1q-C1r-C1s)

activation unit (C4, C2, C3)

membrane attack (C5-C9)

Bacteria, yeast, virus, or tumor cell

C3b, opsonin, substance that “binds” to surface of target cell

C5a, anaphylatoxin, act as mediator of local inflammatory response

Perforates cell membrane of target cell

“Membrane Attack Complex” (MAC) of Complement

Transmembrane channelTransmembrane channelMicelle

Lipid bilayer

Glycocalyx

Membrane Attack Complex

A Different “View” of Complement Activation

C3

C3b

C5 - C9 Terminal Sequence

Ag/Ab Complex

Classical Pathway (Acquired

)

M’organisms

Alternative Pathway (Innate)

Opsonizing (“coating”)

Opsonization by C3b•C3b coatings of cells: --facilitate adherence of bacteria, viruses and other m'organisms to neutrophils, monocytes and macrophages; --facilitate ingestion of certain bacteria by neutrophils and monocytes; --aids ingestion by activated macrophages; --facilitates IgG-induced phagocytosis and cell cytotoxicity.

Opsonin binding

Ab

PMNFcR Y

+

CR3

PMN

C3b

++

Ab

Y

CR3

PMN

FcR

C3b

+++

“Actions” of Complement

C3a and C5a

C3bC5a

MAC(C5-C9)

Activating Stimuli

Bacterial lysis Phagocytosis Chemotaxis Vasodilation Permeability

Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base- Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane

(tissue injury)

Activating Stimuli

Bacterial lysis Phagocytosis Chemotaxis Vasodilation Permeability

Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane

(tissue injury)

Complement ActivationAlternate Pathway

C3 and C5

C3b and C5b

Membrane attackcomplex

Activating Stimuli

Bacterial lysis Phagocytosis Chemotaxis Vasodilation Permeability

Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane

(tissue injury)

Complement ActivationAlternate Pathway

C3b and C5b

Membrane attackcomplex

C3 and C5

Complement ActivationClassical Pathway

C3b

Opsonization

Activating Stimuli

Bacterial lysis Phagocytosis Chemotaxis Vasodilation Permeability

Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane

(tissue injury)

Complement ActivationAlternate Pathway

C3b and C5b

Membrane attackcomplex

C3 and C5

Complement ActivationClassical Pathway

C3b

Opsonization

C3a C5a

(Anaphalytoxins)

Activating Stimuli

Bacterial lysis Phagocytosis Chemotaxis Vasodilation Permeability

Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane

(tissue injury)

Complement ActivationAlternate Pathway

C3b and C5b

Membrane attackcomplex

C3 and C5

Complement ActivationClassical Pathway

C3b

Opsonization

C3a C5a

(Anaphalytoxins)

Mast celldegranulation

Histaminerelease

Activating Stimuli

Bacterial lysis Phagocytosis Chemotaxis Vasodilation Permeability

Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane

(tissue injury)

Complement ActivationAlternate Pathway

C3b and C5b

Membrane attackcomplex

C3 and C5

Complement ActivationClassical Pathway

C3b

Opsonization

C3a C5b

(Anaphalytoxins)

Mast celldegranulation

Histaminerelease

Activating Stimuli

Bacterial lysis Phagocytosis Chemotaxis Vasodilation Permeability

Microbial Surfaces Ag-Ab Complexes Ag-Ab Complexes Collagen base-Polysaccharides (IgG or IgM) (IgE on Mast cells) membrane

(tissue injury)

Complement ActivationAlternate Pathway

C3b and C5b

Membrane attackcomplex

C3 and C5

Complement ActivationClassical Pathway

C3b

Opsonization

C3a C5b

(Anaphalytoxins)

Mast celldegranulation

Histaminerelease

Hageman factor

Coagulationcascade

KallikreinActivation

Bradykinin

Animations

• Complement Animations & Online Quiz• Complement Animations & Quiz