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C4d: Good or Bad?

C4d: Good or Bad?. C4b. C4b. C4. C4b. C4d. C4d. C4b. C1qrs. Factor I. C2. Saadi et al. J Exp Med 182: 1807, 1995. How to Detect Humoral Rejection. Dysfunction of graft Anti-donor antibodies in the blood Ig deposits Complement deposits Platelet count Fibrin RBC morphology.

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C4d: Good or Bad?

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  1. C4d: Good or Bad?

  2. C4b C4b C4 C4b C4d C4d C4b C1qrs Factor I C2

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

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

  5. 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

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

  7. Healthy EC Sick EC Complement Removes Immune Complexes

  8. Normal Lung Transplanted Lung

  9. vWF C3 Liver Spleen

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

  11. C4 C4b C4d C4d C4d C4d C4d C4d C4d Complement Bocks Reactive Sites

  12. Accommodation Anti-A titer 1:64

  13. C4d in Accommodation

  14. No Complement Complement Pre-treated

  15. Ca2+ Ca2+ Ca2+ C5a ? MAC MAC Gi Raf Ras Ca2+ Raf JAK STAT Gi STAT Gq ADENYL CYCLASE PLCb2 STAT PI-3K Atk STAT PLCb2 MEK-1 PI-3K cAMP DAG IP3 DAG ERK-1 S6k ERK-1 PKC Ca2+ PKC Nucleus

  16. 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

  17. MASP C1rs MBP C1q H C3b Bb

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

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

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

  21. Cardiac Xenograft After Kidney Perfusion

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

  23. IgM Binding Lung Heart

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