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Jan ew ay 9.4 9 par t 2. Roi tt 12. 22 Roi tt 4.1.

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Presentation on theme: "Jan ew ay 9.4 9 par t 2. Roi tt 12. 22 Roi tt 4.1."— Presentation transcript:

1 Jan ew ay par t 2

2 Roi tt

3 Roi tt 4.1

4 The Classical Activation Pathway Some large fragments function by binding to membranes (esp. pathogen membranes) Some small fragments act as soluble mediators C1s C4 Ab C4a C4b C3 C3a C5 C5a C5b C6C7 C8 C9 C6 C7C8C9 MAC Membrane Ucker, 2003 Classical Activation Pathway C2 C2b C4b C2a C3b C1

5 Roi tt 4.2

6 Jan ew ay 9.3 6

7 Activation of C4 A CTIVATION O F C4 C4b C4 C1s Ucker, 2003 C4a C4 C1s

8 Thioester mediated binding of C4b Pathogen C4 C4a C4b T HIOESTER- M EDIATED B INDING O F C4b T O T HE S URFACE O F A P ATHOGEN Ucker, 2003 C4b

9 Activati on of a C3 Convert ase A CTIVATION O F A C3 C ONVERTASE C2 C4b Pathogen Thioester-mediated binding to the pathogen: Ucker, 2003 C1s C2a C2b C4b C2 C4b

10 Roi tt 4.7

11 Thioester mediated binding of C3b Pathogen C3 C3a C3b T HIOESTER- M EDIATED B INDING O F C3b T O T HE S URFACE O F A P ATHOGEN Ucker, 2003 C3b

12 Roi tt 4.1 6

13 Roi tt A

14 Roi tt pan el 1

15 Jan ew ay par t 2 & Ma yer Fig ure s 6,8 Relative sensitivity of nucleated and non-nucleated cells to membrane attack C6 (relative concentration) Cells stained by vital dye (%) Time (minutes)Channels remaining (%) Temperature-dependent repair by nucleated cells of Complement channels (M. Mayer 1984)

16 Jan ew ay 9.3 2

17 Gly can stru ctur es N-Acetyl Glucosamine Complex Sialylated Fucosylated Glycan Sialic Acid Galactose Mannose Fucose High Mannose Glycan Ucker, 2003

18 Roitt4.8Roitt4.8

19 Thioester mediated binding of C3b Pathogen C3 C3a C3b T HIOESTER- M EDIATED B INDING O F C3b T O T HE S URFACE O F A P ATHOGEN Ucker, 2003 C3b

20 R o itt

21 Amplification Loop C3b B C3bB D Ba C3bBb C3 C3a (C3 convertase) C3 One C3 convertase molecule cleaves many C3 molecules. Properdin stabilization C3b interacts with factor B, and more C3 convertase is generated. Amplificat ion Loop Hanley, 1998

22 Roitt12.13bRoitt12.13b

23 Three families of Complement proteins Ucker, 2003

24 Ucker, 2000 Complement is a self-limiting cycle

25 Regulators Of Complement Activation Regulators of C3 convertase assembly and destruction: C4b-BP, MCP, CR1, Factor H, DAF (assembly), Factor I (destruction) Regulators of the lytic pathway (MAC assembly inhibitors): HRF, MRL Regulators of C1 esterase activity: C1 INH (Deficiency = Hereditary Angioneurotic Edema) Ucker, 2000 Regulators Of Complement Activation

26 Roitt4.7Roitt4.7

27 Roitt4.12Roitt4.12

28 Com plem ent Contr ol Prote ins (adap ted from Jane way 9.50)

29 ComplementReceptors (adapted from Roitt4.15)ComplementReceptors (adapted from Roitt4.15)

30 Activati on of C3 A CTIVATION O F C3 C3 C2a4b C3a C3b Ucker, 2003 Pathogen

31 Roitt18.16Roitt18.16

32 Roitt12.22Roitt12.22

33 C1 C4 C2 B D Properdin C3 (I, H) C5 C6 C7 C8 C9 Pyogenic infections Immune Complex Disease Neisserial infections Severe pyogenic infections Immune Complex Disease Neisserial infections Deficiencies of components within the same pathway result in similar clinical manifestations. Hanley, 1998

34 Jan ew ay 9.3 1


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