Effector mechanisms of humoral immunity The Complement System (C’) Activation pathways Effector functions Regulation of complement activation.

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Presentation transcript:

Effector mechanisms of humoral immunity The Complement System (C’) Activation pathways Effector functions Regulation of complement activation

Jules Bordet ( ) Nobel prize For complement-mediated bacteriolysis Complement system (complements i.e. assists functions of antibody)

Consists of serum and cell surface proteins involved in defense against pathogens and tissue damage mediated by antibodies Effector mechanism of both innate and adaptive humoral immunity Complement system

Over 30 serum and cell surface proteins: - Complement components (in serum inactive, activated sequentially as a cascade) - Complement receptors (cell surface, recognize activated components) - Regulatory proteins of complement (both in serum and cell surface, inhibit activated components) Complement system

Pathways of activation - Classical - Alternative - Lectin Complement system

Activation and functions of complement (overview)

Classical Lectin Alternatve C1, C4, C2 Early stepsLate steps MBL, C4, C2 C3, B, D (P) C3, C5, C6, C7, C8, C9 Activation pathway

Classical Lectin Effector functions (elimination of pathogen) C3 convertase Alternatve Ag-Ab complex (microorganism and IgG or IgM Ab) microorganism C5 convertase b a Early stepsLate steps C1 MBL C3 C4 C2 D B

Early steps of complement activation D B P MASP MBL

Late steps of complement activation

C1 Activated C4b2b C3 CONVERTASE C5 C9C8C7C6 Bacterium IgG IgM C4 C2C2 C4aC4b C2bC2bC2aC2a C3C3 C3aC3b C4b2b3b C5 CONVERTASE C5aC5b Lysis MEMBRANE ATTACK COMPLEX C5-C9 MAC

C4b2b C3 CONVERTASE C5 C9C8C7C6 Bacterium C4 C2C2 C4aC4b C2bC2bC2aC2a C3C3 C3aC3b C4b2b3b C5 CONVERTASE C5aC5b Lysis MEMBRANE ATTACK COMPLEX C5-C9 MAC MASP MBL

C3C3b C5 C6C7C8C9 Bacterium Factor D BaBb C3 C3aC3b C3bBb3b Alternative C5 convertase C5b C5a Lysis MEMBRANE ATTACK COMPLEX C5-C9 MAC Factor B C3bB C3bBb Alternative C3 convertase Properdin

Effector functions of activated complement - Cytolysis (MAC)

Cytolysis (MAC)

Effector functions of activated complement - Cytolysis (MAC) - Opsonization (C3b, C4b)

Opsonization and phagocytosis (C3b, C4b)

Effector functions of activated complement - Cytolysis (MAC) - Opsonization (C3b, C4b) - Stimulation of inflammation (C5a, C3a, C4a)

Stimulation of inflammatory rections (C5a, C3a, C4a) Activation of mast cells and neutrophils (anaphylatoxins)

Effector functions of activated complement - Cytolysis (MAC) - Opsonization (C3b, C4b) - Stimulation of inflammation (C5a, C3a, C4a) - Stimulation of humoral response (C3d)

Stimulation of humoral immunity (B cells)

Effector functions of activated complement - Cytolysis (MAC) - Opsonization (C3b, C4b) - Stimulation of inflammation (C5a, C3a, C4a) - Stimulation of humoral response (C3d) - Immune complex clearance (C3b)

Immune complex clearance (C3b)

Regulatory proteins of complement

Complement system (animation)

Laboratory tests for complement assesment Quantification of compoments (C3, C4, MBL - RID, nephelometry) - concentration: g/L (mg/ml) Functional tests for classical and alternative pathway of activation

10.____9.____8.____7.____5._____4._____3._____2._____ C3a, C4a and C5aj.Osmotic lysis of microbes are mediated by10. C3bi.Inflammatory reactions are induced by9. MACh.Important opsonin is 8. C3 componentg.Proteins involved in early steps of classical pathway are 7. IgM and IgG bound to antigenf.Components of alternative pathway are6. C1, C4, C2e.Activators of classical pathway are5. classical, alternative and lectind.First component in lectin pathway is4. factor B, factor D, properdinc.Central role in complement activation belongs to 3. effector mechanism of innate and adaptive immunity b.Complement activation pathways are2. mannose binding lectin (MBL)a.Activation of complement system is1. 1._____6.____ dgafceijbh