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Complement
- 3. LEARNING OBJECTIVE • Define complement • Components of complement • Activation of complement • Check points • Deficiencies
- 4. HISTORY • Buchner (1889) – Destruction of bactericidal activity of serum when heated at 55 C for one hour. • Pfeiffer phenomenon (1894)- Lysis of cholera vibrio – Immunised guinea pig. • Bordet – Heat stable factor & Heat labile factor ( Alexine) • Ehrlich – Complement for the heat labile factor.
- 5. PROPERTIES OF COMPLEMENT • Omnipresent – all living things. • Non specific and inter-species reactable. • 5% of the normal serum proteins • Destroyed when heated at 56 C for 30 minutes.
- 6. • Never ever increased by immunisation. • They are antibody related ; not antigen. • Normally in inactivated form; Activated by Ag – Ab combination. PROPERTIES OF COMPLEMENT
- 7. IMMUNOGLOBULIN & COMPLEMENT • Not all imunoglobulins are complement fixators. • Binding site – Fc portion of Ab ( when binds with antigen) • IgM > IgG3 > IgG1 > IgG2. • IgG 4, Ig A, IgD & IgE – DONOT FIX.
- 8. Ag
- 10. COMPONENTS • Nine different fractions – C1 to C 9. • C1 – Calcium ion – dependent + EDTA = C1q, C1r, C1s --------11 fractions. • C1 -----C4-------C2. • Activated ------ C3 • Inactivated – i C3 • Fragments – C3a (Smaller), C3b (Bigger)
- 11. BIOSYNTHESIS OF COMPLEMENT • C1 – Intestinal epithelium • C2,C4 – Macrophages • C5,C8 – Spleen • C3,C6,C9 – Liver. • Acute phase of inflammation – C3,C4,C5,C6
- 12. PATHWAYS • Classical pathway ( Specific; active) • Alternative (Properdin )pathway • Lectin Pathway - ( Non specifc; Innate) Series of reactions known as CASCADE
- 14. CLASSICAL PATHWAY The sequence of events following the activation of C1 resulting in immune response Activators 1. Ag – Ab complex 2. DNA 3. CRP 4. Trypsin 5. Retroviruses
- 15. Calcium ions
- 16. C2b , C4a,C3a
- 19. ALTERNATE PATHWAY The activation of C3 without participation of C4b2a known as alternate pathway Activators 1. Zymosan ( Yeat cell wall) 2. Bacterial endotoxins 3. Cobra venom 4. Nephritic factor (GN pts) 5. Ig A, Ig D
- 21. LECTIN PATHWAY A pathway where lectin & mannose activates the complement ACTIVATORS Lectin – Mannose complex to pathogens (Mannose specific protease – MASP 1 & MASP 2)
- 25. 1. Which of the following pathway is antidody independent? a. Classical pathway b. Properdin pathway c. Lectin pathway d. Alternate pathway Ans: b & d
- 26. 2. Which one of these is called as classical C3 convertase? a. C4b2b b. C4b2a c. C5a6b d. C5b6a Ans: b
- 27. 3. Which one of these is classical C5 convertase? a. C4b2a3b b. C1a2a3a c. C4a2a3a d. C56789 Ans: a
- 28. EFFECTOR FUNCTIONS • Lysis of cells or bacteria. • Viral neutralisation • Opsonisation & Phagocytosis • Immune clearance – deposition in liver & spleen • Amplify inflammatory response, increase vascular permeability,release of histamine.
- 31. REGULATION 1. Inhibitors – Halts further progression C1s INH – C1 S protein – act C67 2. Inactivators – Destroys complement proteins. Factor I – C3 Factor H – C3 C4 binding protein – C4b Anaphylotoxin inactivator – C3a,C4a & C5a
- 33. Deficiencies of the complement system GROUP DEFICIENCY SYNDROME I C1 inhibitor Hereditary angioneurotic edema II Early components of classical pathway C1,C2,C4 SLE & other collagen vascular diseases III C3 and C3b inactivator Severe recurrent pyogenic infections IV C5 to C8 Bacteremia – GN diplococci, toxoplasmosis V C9 -----------
- 35. QUANTITATION OF COMPLEMENT 1. Radial immunodiffusion 2. Hemolytic system
- 36. PATHOGEN EVADING COMPLEMENT 1. Cell wall lipopolysacchride 2. Peptidoglycan 3. Capsule 4. Proteins
- 39. Questions??????? Short notes 1. Classical pathway 2. Alternate pathway 3. Lectin pathway 4. Complement deficieny 5. Biological effects of complement 2 marks 1. Inhibitors & inactivators 2. Pfeiffer phenomenon 3. Activators of complement pathway 4. Hereditary angioneurotic edema