1. Complement Male, Immunology, 2006 Zipfel, Nature, 2009 Mobeen Syed ب Dr. Yıldıran1

2. Objectives You should say: Basic functions How works Its place and importance in immune reactions Dr. Yıldıran2

3. Non-specific immunity (Innate) Specific immunity (Adaptive) Immune System Delayed reaction MEMORY! Fast reaction Dr. Yıldıran3

4. Immune Response Abbas, 2003 Dr. Yıldıran4

5. Serum vs Plasma If you wait blood in a glass tube, blood coagulated, serum separated It does not contain fibrinogen Dr. Yıldıran5

6. Complement System Many plasma proteins, nine are essential. 10% of plasma proteins as pro-enzymes It was named as ‘Complement’ in 19th century because of thinking about it completes bactericidal feature of serum. Dr. Yıldıran6

7. Complement Proteins C1, C2, C3, C4, C5, C6, C7, C8, C9 Underlined parts do not cleaved When cleaved; C2b (big part) and C2a (anaphylaxis part) C6, C7, C8, C9 are not enzymes C6, C7, C8 binded with C9 Main activating molecule is C3 Dr. Yıldıran7

8. Basic Function Recognizing and clearing the FOREIGN For this, Complement –Starts and increases inflammation –Increases chemotaxis and phagocytosis –Cleares immune complexes –Activates cells –Kills directly –Provides antibody response. Dr. Yıldıran8

9. Functions in Inflammation C3b Dr. Yıldıran9

10. Four Plasma Cascades Pain Plug DIC Inflam. Dr. Yıldıran10

11. Simple Mechanism IgG and IgM C1 C4  Innate arm Spontaneous activation Endotoxin C3 and B C3  Adaptive arm Antibody activation Dr. Yıldıran11

12. Dr. Yıldıran12 EDEMA

13. C1qrs Electron Microscobe Dr. Yıldıran13

14. Membran activating complex Elektron Mikroskobu ile Dr. Yıldıran14

15. Some Functions C5a → Chemotaxis, inflammation C3a and C5a (Anaphylotoxins) → Mast cell and basophil activation (Anaphylaxis), inflammation C3b → –Opsonisation, –Clearing immune complexes, –B cell activation –Clearing apopitotic cells –Asplenic patients can not grab C3b-bacteria complex –Increases plasma cell antibody secretion MAC → Lysis of Gr negative (Especially Neisseria) some viruses Dr. Yıldıran15

16. Clinical evaluation C3 (0.75-1.61 g/L) C4 (0.2-0.5 g/L) CH50 → Classical pathway AH50 → Alternative pathway Dr. Yıldıran16

17. Control of Complement System IF not Autoimmunity Dr. Yıldıran17

18. CD18CD11b,c PNH Dr. Yıldıran18

19. Regulation P (Properdin)stabilizes C3bBb and prevent inactivation by H,I D cleaves B to Bb Properdin and Factor D deficiencies are PID Factor H binds C3b Factor I destroys C3b-factor H complex C1 inh, regulates classical pathway inhibiting C1q and s Dr. Yıldıran19

20. In disease Atypical HUS (no diarrhea): heterozygot factor H mutation Dense deposite disease (MPGN II): homozygot or compound heterozygot C3 or factor B (C3 convertase stage), otoantikor oluşumu (C3 nephritic factor) Age-related macular degeneration: retinal Bruch membrane or glomerule basal membrane; factor H or C3 mutation Dr. Yıldıran20

21. Autoimmune diseases C1q and C4 deficiency: clearing of apopitotic cells impairs. Homozygot defects in C1q, C1r, C1s, C2, C3 or C4 genes: rheumatic diseases, especially SLE. C1qinh defect → Hereditary angioedema Dr. Yıldıran21

22. Tumors In some tumors, inhibitors of complement on cell membrane (CD46, CD55, CD59) changed. soluble regulators (factor H, factor I, C4BP) expression increased on lung, ovary, glial and bowel cancer cell membranes and plasma. Namely, tumor cells hide from CD8 cytotoxic cells. Dr. Yıldıran22

23. Eculizumab C5 monoclonal antibody Inhibits complement system on C5 convertase. Dr. Yıldıran23

24. Hereditary angioedema Dr. Yıldıran24

25. Neonatal Lupus Dermatology.cdlib.org Dr. Yıldıran25

26. Meningococcemia Dr. Yıldıran26