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
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2. CONTENTS
1. INTRODUCTION
2. COMPLEMENT SYSTEMS (CS)
3. PATHWAYS OF CS-
a. CLASSICAL PATHWAYS
b. ALTERNATIVE PATHWAYS
c. LECTIN PATHWAYS
4. MEMBRANE ATTACK COMPLEX (MAC)
5. CONCLUSION
6. REFERENCES
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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.
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4. COMPLEMENT PATHWAYS
There are three pathways of complements
systems:
1. Classical pathways
2. Alternative pathways
3. Lectin pathways
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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.
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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).
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3
4
FIG.: stages of classical pathway
of complement system

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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 .
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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).
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C5 convertase
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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
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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).
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2
FIG.: activation of lectin pathway

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13. MEMBRANE ATTACK COMPLEX (MAC)
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 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 .
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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.
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16. REFERENCES
 Charles A Janeway ,Mark Shlomchik . The immune system
in health and disease . 5th edition.
 Abdul K. Abbas, Andrew H. Lichtman . Basic Immunology .
5th edition.
 Goldsby, R.A. ,Kindt, T.J., B.A., Kuby . Immunology . 5th
edition.
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