1. C4d: Good or Bad?

2. C4C4b C4d C1qrs C4b Factor I C4d C2

4. Saadi et al. J Exp Med 182: 1807, 1995

6. How to Detect Humoral Rejection Dysfunction of graft Anti-donor antibodies in the blood Ig deposits Complement deposits Platelet count Fibrin RBC morphology

7. What Could Be Good About C4d? Complement, particularly C4, inhibits humoral immunity Complement removes immune complexes C4d blocks reactive sites Complement repairs endothelium Complement and/or Ab induces Accommodation

8. CR2 (C4b receptor) suppresses auto-immunity C4 Facilitates clearance of immune complexes SLE associated with C4 deficiency C4 deficiency Impairs clearance of apoptotic cells Regulation of Humoral Immunity by C4 and its Receptors

9. Healthy ECSick EC Complement Removes Immune Complexes

10. Normal LungTransplanted Lung

11. vWFC3 Liver Spleen

12. Saadi and Platt J Exp Med 181: 21, 1995 Complement Repairs Endothelium

13. C4d C4C4bC4d Complement Bocks Reactive Sites

14. Anti-A titer 1:64 Accommodation

16. C4d in Accommodation

17. Complement Pre-treated No Complement

18. Nucleus Ca 2+ Gi STAT MAC Raf Ras MEK-1 PI-3K ERK-1 Atk S6k STAT Raf JAK STAT MAC cAMP ADENYL CYCLASE Gi PLCb2 PKC Ca 2 + GG ? C5a DAG IP 3 PI- 3K ERK- 1 PLCb2 PKC DAG

19. Caveats of Accommodation May allow organ to survive long enough to acquire chronic rejection May fail to avert whatever causes chronic rejection May cause chronic rejection

22. C1q C1rs MBP MASP C3b Bb H

25. Organ Transplantation Hyperacute Rejection Acute Vascular Rejection Accommodation Cellular Rejection Chronic Rejection

26. Collins BA, et. al. JASN 10:2208, 2000 C4d deposition in peritubular capillaries

27. C4d: Good or Bad? How C4d helps How complement harms How complement benefits

30. Cardiac Xenograft After Kidney Perfusion

32. The Need for C4d Kidneys absorb Ig very well Bound Ig disappears by endocytosis and shedding Some Ig binds “non-specifically”

33. Lung Heart IgM Binding