Complement system

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A brief description of complement pathways

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Complement system:

Varun C N www.microboids.net Complement system

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Varun C N- Complement system 2

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Complement system pathways: Classical pathway Alternative Pathway Lectin pathway Varun C N- Complement system 3

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Daniel Ricklin & John D Lambris Nature Biotechnology 25, 1265 - 1275 (2007 ) Varun C N- Complement system 4

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Varun C N- Complement system 5 Activation of complement system C3 convertase C5 convertase MAC

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Complement system 6 Structure of C1 molecule Source: Kuby; 5 th ed Classical Pathway

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Varun C N- Complement system 7

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Varun C N- Complement system 8 Alternative pathway

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Varun C N- Complement system 9 http://www.crystal.chem.uu.nl/~gros/figs/cvf-b-large.jpg

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Varun C N- Complement system 10 http://www.crystal.chem.uu.nl/~gros/figs/c3bbd-large.jpg

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Varun C N- Complement system 11 Activation of the terminal complement pathway results in formation of membrane-attack-complexes (MAC) that form large (100 Å wide) pores in the target membrane. http://www.crystal.chem.uu.nl/~gros/complement.html

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Varun C N- Complement system 12

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Varun C N- Complement system 13 Classic Alternative First reactant C1q C3b Reaction trigger Antigen Antibody complex Microbial products C3 convertase C14b2a C3bBb C5 convertase C14b2a3b C3bBb3b

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Varun C N- Complement system 14 Component Biological Activity C2b Prokinin ; cleaved by plasmin to yield kinin , which  results in edema C3a Anaphylotoxin ; can activate basophils and mast cells to degranulate resulting in increased vascular permeability and contraction of smooth muscle cells, which may lead to anaphylaxis C3b Opsonin ; promotes phagocytosis by binding to complement receptors Activation of phagocytic cells C4a Anaphylotoxin (weaker than C3a) C4b Opsonin ; promotes phagocytosis by binding to complement receptors

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Varun C N- Complement system 15 Kuby; 5 th ed

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Complement system 16 Thurman etal. Laboratory Investigation (2011) 91, 4–11 Nature Publishing group

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Varun C N- Complement system 17 Kuby; 5 th ed Functions of complement system

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18 Complement system Disease Mechanism C1INH Hereditary angioedema Overproduction of C2b ( prokinin ) C1, C2, C4 Predisposition to SLE Opsonization of immune complexes help keep them soluble, deficiency results in increased precipitation in tissues and inflammation Classical Pathway Gene Mayer; Immunology Deficiency of complement components and associated disease

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Complement system 19 Factors B or D Susceptibility to pyogenic (pus-forming) bacterial infections Lack of sufficient opsonization of bacteria C3 Susceptibility to bacterial infections Lack of opsonization and inability to utilize the membrane attack pathway C5 , C6, C7 C8, and C9 Susceptibility to Gram-negative infections Inability to attack the outer membrane of Gram-negative bacteria Properdin (X-linked) Susceptibility meningococcal meningitis Lack of opsonization of bacteria Factors H or I C3 deficiency and susceptibility to bacterial infections Uncontrolled activation of C3 via alternative pathway resulting in depletion of C3 Alternative Pathway Gene Mayer; Immunology

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