Complement system:key features, role of the C3

convertases and activation ofpathways

Immunologie SeminarFabian Schulze Bisping

27.10.2014

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The complement system

Part of the innate immune system

Also influences adaptive immune system

Comprised of more than 30 soluble proteins

Proteases initially circulating aszymogens

Activation of complement zymogensresults in proteolytic cascade

Janeway, Immunology p 50 fig 2.11

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The C3 convertases

Janeway, Immunology p 51 fig 2.12

All 3 pathways utilize a C3 convertase toachieve complement activation

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The C3 convertases

Janeway, Immunology p 52 fig 2.13

Cleaving of C3 by C3 convertase reveals thioester bound to C3b

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The lectin pathway

Janeway, Immunology p 53 fig 2.14

Janeway, Immunology p 54 fig 2.15

Carbohydrate patterns on yeast and vertebrateglycoproteins

mannose-binding lectin (MBL) and ficolincomplexes

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The lectin pathway of activation

Janeway, Immunology p 55 fig 2.16

Activation of the C3 convertase through MBL/ficolin-MASP-complexes

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The classical pathway

Janeway, Immunology p 55 fig 2.18

Janeway, Immunology p 55 fig 2.17

C1 complex comprisedof C1q, C1s and C1r

Proteins of the classical pathway activation

Classical pathway activation is highlysimilar to lectin pathway activation

C1 binds either directly to pathogensurface or to pathogen-bound antibodies

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Confinement of complement activation to activatingsurface

C4 cleaving by C1s or MASP-2 occurs close to pathogen surface- C4b more probable to bind to pathogen surface

C2 binding to C4b and subsequent cleaving of C2 by C1s or MASP-2- C2a remains bound to C4b confining C4b2a to pathogen surface

Confiment of C4b2a C3 convertase to pathogen surface- C3 cleaving in close proximity to initially activating surface

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Proteins of the alternative pathway

Janeway, Immunology p 59 fig 2.22

Proteins of the alternative pathwayof activation

2 mechanisms for initiation of thealternative pathway

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Activation of the alternative pathwayas as a result ofclassical or lectin pathway

Janeway, Immunology p 58 fig 2.19

Surface-bound C3b binds factor B- creation of alternative C3 convertase C3bBb

Amplification of the C3b deposition on the surface

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Spontaneous activation of the alternative pathway

Janeway, Immunology p 58 fig 2.20

Spontaneous hyrdolysis of C3 enables binding of factor B

Creation of shortlived C3 convertase

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Alternative C3 convertase is stabilized byproperdin (factor P)

Janeway, Immunology p 59 fig 2.21

Properdin (factor P) can stabilize C3bBb

May posses pattern recognition properties

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