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 Pathway Classical Pathway Assembly of the Terminal 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 channel Micelle 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 PMN FcR Y + CR3 PMN C3b ++ Ab Y CR3 PMN FcR C3b +++

“Actions” of Complement C3a and C5a C3b C5a 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 Activation Alternate Pathway C3 and C5 C3b and C5b Membrane attack complex

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 Activation Alternate Pathway C3b and C5b Membrane attack complex C3 and C5 Complement Activation Classical 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 Activation Alternate Pathway C3b and C5b Membrane attack complex C3 and C5 Complement Activation Classical 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 Activation Alternate Pathway C3b and C5b Membrane attack complex C3 and C5 Complement Activation Classical Pathway C3b Opsonization C3a C5a (Anaphalytoxins) Mast cell degranulation Histamine release

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 Activation Alternate Pathway C3b and C5b Membrane attack complex C3 and C5 Complement Activation Classical Pathway C3b Opsonization C3a C5b (Anaphalytoxins) Mast cell degranulation Histamine release

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 Activation Alternate Pathway C3b and C5b Membrane attack complex C3 and C5 Complement Activation Classical Pathway C3b Opsonization C3a C5b (Anaphalytoxins) Mast cell degranulation Histamine release Hageman factor Coagulation cascade Kallikrein Activation Bradykinin

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