Complement System.pptx

Elaborate about the complement system, the pathway of complement system, the Membrane Attack Complex.

1. SEMINAR PRESENTATION TOPIC: PATHWAYS OF COMPLEMENT SYSTEMS PAPER: 403-C PRESENTED BY:- PARAG PATGIRI MSC. ZOOLOGY ZOOLOGY DEPARTMENT BODOLAND UNIVERSITY GUIDED BY Dr. ANANTA SWARGIARY ASSTT. PROFESSOR ZOOLOGY DEPARTMENT BODOLAND UNIVERSITY 1

2. CONTENTS INTRODUCTION COMPLEMENT SYSTEMS (CS) PATHWAYS OF CS- CLASSICAL PATHWAYS ALTERNATIVE PATHWAYS LECTIN PATHWAYS MEMBRANE ATTACK COMPLEX (MAC) CONCLUSION REFERENCES 2

3. INTRODUCTION The complement system is a biochemical cascade that helps clear pathogens from an organism . Complement is a system of plasma proteins that enhances the ability of antibody and phagocytic cells to clear microbes from an organism and attack the pathogen’s cell membrane. It is a part of innate immune system . Complement activation pathways involves the activation of one components that triggers the activation of next component in the sequences. Complement activation leads to the lysis of cell. 3

4. COMPLEMENT PATHWAYS There are three pathways of complements systems: Classical pathways Alternative pathways Lectin pathways 4

5. 1. CLASSICAL PATHWAYS Begin with the formation of antigen-antibody interaction. Only IgM and subclasses of IgG can activate thses pathway. When Ag- Ab complexes occur, conformation changes in the Fc portion of antibody molecule that exposes a binding site for the C1 component. C1 has three different proteins: C1q , C1r , C1s . First C1q binds to the Ag- ab complexes and activate C1s and C1r. C1s and C1r act asproteases that cleaves other C proteins. 5 1 2

6. C1s cleaves C4 into C4a and C4b and C2 into C2a and C2b. C4b and C2a bind together and form C4b2a complex called c3 convertase . The C4a and C2b ,which is the smaller fragments are diffuses away. Then C3 convertase hydrolyzes C3 into C3a and C3b. C3b binds to C4b2a and form C4b2a3b, called C5 convertase . Again C5 convertase hydrolyzes C5 into C5a and C5b. C5a diffuses away and C5b attaches toC6 and C7 that interact wiuth C8 and C9 and form membrane attack complex (MAC). 6 3 4 FIG.: stages of classical pathway of complement system

7. 7 FIG.: Flowchart of classical pathway of complement system

8. 2. ALTERNATIVE PATHWAY It is an antibody independent pathway. It is activated by some bacterial cell surfaces. Activation of this pathway involves four serum proteins : C3, factor B, factor D and factor P. C3b component of C3 binds to foreign antigen . Factor D cleaves factor B into Ba and Bb. C3b bind Bb , forming C3bBb,called C3 convertase . C3 convertase hydrolyzes C3 into C3a and C3b . 8 1

9. Bb attaches to the complex and form (C3b)2Bb, called C5 convertase . Ba smaller fragment diffuses away C5 convertase work on C5 and hydrolyzes it into C5a and C5b. C5a diffuses away and C5b attaches to C6 and C7 that interact with C8 and C9 and form membrane attack complex (MAC). 9 C5 convertase 2 Fig .: Stages of alternative pathway

10. 3. LECTIN PATHWAY C4a and C2b diffuses out. Antibody independent pathway. Mannose residue are present on the bacterial cell wall. Mannose binding lectin (MBL) recognize and bind to the mannose residues. MBL-associated serine proteases ( MASP1, MASP2) bind to MBL and form complex. This complex activates C4 and C2 and cleaves and together form C4b2a ,called C3convertase, where smaller fragments 10 1

11. Then C3 convertase hydrolyzes C3 into C3a and C3b. C3b binds to C4b2a and form C4b2a3b, called C5 convertase . Again C5 convertase hydrolyzes C5 into C5a and C5b. C5a diffuses away and C5b attaches toC6 and C7 that interact wiuth C8 and C9 and form membrane attack complex (MAC). 11 2 FIG.: activation of lectin pathway

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13. MEMBRANE ATTACK COMPLEX (MAC) 13 The terminal stage of classical pathway involves the creation of pores on the pathogen’s membrane called membrane attack complex (MAC). The complement proteins (C5b, C6,C7,C8,C9) assemble together to form MAC on the target cell membrane. Multiple C9 proteins bind to the complex and form pore or channel on the target cell. This pore allows water and ions to enter the cell , ultimately lysis of target cell. FIG.: Membrane attack complex (MAC)

14. FIG .: Flowchart of activation of complement systems through three different pathways . 14 1 2 3

15. CONCLUSION Complement plays a central role in the immune systems by its supporting roles in the clearances of apoptotic cells. The complement systems plays a vital role in enhancing the ability of antibody and phagocytic cells to clear pathogens and damaged cells from the host body. Deficiency of complement factors may lead to complement associated diseases, on the contrary regulation of complement activation is also necessary to avoid damage to host tissues and normal functioning of the immune system. 15

16. REFERENCES Charles A Janeway ,Mark Shlomchik . The immune system in health and disease . 5 th edition. Abdul K. Abbas , Andrew H. Lichtman . Basic Immunology . 5 th edition. Goldsby , R.A. , Kindt , T.J., B.A., Kuby . Immunology . 5 th edition. 16

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