immunology lecture 7: complement

complement

- a group of serum proteins circulating in an inactive form

- complement proteins cooperate with both immune systems

- once activated, complement plays a role in amplification, opsonization, inflammation, + lysis

initiators

- initiate specific reactions after binding soluble or membrane-bound molecules

enzymatic mediators

- proteolytic enzymes or zymogens

opsonins

- bind covalently to microbial cells + serves as ligands for phagocytic cells

inflammatory mediators

- anaphylatoxins cause vascular permeability + leukocyte chemotaxis

membrane attack proteins

- punch holes in the membranes of invading pathogens

- complement receptors

- bind complement + signal specific cell functions (phagocytosis, neutrophil degranulation)

regulators

- protect host cells from unintended consequences

complement activation pathways

- complement cascade can be initiated by 3 major pathways: classical, lectin, + alternative

- all pathways converge in the generation of C3 convertase

- addition of C3b to C3 convertase results in generation of C5 convertase

C3b complement protein

- protects host through:

- opsonization: C3b binds covalently to microbial surfaces, providing a tag allowing recognition by phagocytes

- antigen-antibody complexes: C3b can attach to the Fc portions of Abs allowing for phagocytosis or movement to liver for elimination

- C5 convertase: C3b can bind to complement protein complexes to form C5 convertase

classical pathway

- initiated by antibodies (either IgM or IgG) binding to antigen

- C1 binds to Ag-AB complex which cleaves C4 + C2, forming C2a, C2b, C4a, C4b

- C2a and C4b combine to form C3 convertase

- C3 convertase combines with C3b to form C5 convertase

lectin pathway

- initiated by binding of lectins (MBL) to microbial carbohydrates

- MBL binding to microbe activates MASPs which cleave C4 and C2 to create C3 convertase which cleaves C3 and forms + cleaves C5

alternative pathway

- may be initiated by tickover pathway

- results in generation of enzymes that cleave C3 and C5

C5 convertase

- C5 generates membrane attack complex (MAC)

- MAC is the result of C5b, C6, C7, C8, and C9 deposition on target cell membranes

- the pore structure disrupts osmotic integrity, resulting in cell lysis + death