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Kush Shrivastava PhD Scholar Division of Animal Genetics I.V.R.

I Izatnagar , Bareilly

Meaning - help, make complete In Immunology - The complement system


helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism.

Primarily the part of Innate Immune System of


an organism.

Hans Ernst August Buchner -

Alexin

Jules Bordet Properties of Alexin Paul Ehrlich Coined term

Complement

Group of about 30 different proteins.

Found free in serum or as cell bound receptors. Named with prefix C (e.g. C1, C2, C3 etc) or designated by letters. Synthesis Various sites like liver, macrophages. Three pathways of activation Classical pathway
Alternative pathway Lectin pathways

C3 convertase A protease , central to all three pathways.

C1

C1q

C4

C2

C3

C1r

C1s

C5

C7

C9

C6

C8

C3 Central components of complement system Has highly reactive thioester group. Needs activation, can bind to surface of many pathogens (as well as normal tissue) & mark them for destruction by immune cells. Highly regulated molecule Factors I & H are involved in regulation of C3 level

ALTERNATIVE PATHWAY OF COMPLEMENT ACTIVATION & REGULATION OF C3 C3b C3 C3a


SPONTANEOUS BREAKDOWN

In the presence of an activating surface

C3b
Under Normal Circumstances (No activating surface)

Ba B
C3bBb

H
C3bBb

D
C3bH

I
C3bBbP

Inactivated C3b P

BASIC FEATURES OF CLASSICAL COMPLEMENT PATHWAYS


Ag + Ab

Inactive C1

Active C1

C4a

C4

C4b

C2

C4b2b C4b2a C4b2

C3b C3a C3

COMPLEMENT ACTIVATION BY LECTIN PATHWAY


Bacterial surface C2

Mannose Binding Lectin

C4b C4a C4

Inactive MASP-2

Active MASP- 2

C4b2b C4b2a C4b2 C3b C3a C3

THE TERMINAL COMPLEMENT PATHWAY


C3b
C5

C3b5b C3b5 5a

C3b5b C3bBb C4B2b

C7

C6

C8

C9

Various fractions formed have different functions.

Regulated by complement control proteins. Present at a higher concentration in the blood plasma than the complement proteins. Some are present on membrane of self cells.

For e.g., CD59, (protectin) which inhibits C9


polymerisation during the formation of the membrane attack complex, C1 inhibitor inhibits the activity if C1 during the classical pathway.