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Complement

The complement system consists of approximately 30 soluble proteins that are crucial for the innate immune response, activated through classical, alternative, and lectin pathways. Each pathway leads to the formation of a membrane attack complex that lyses target cells. The document details the mechanisms of activation and regulation of these pathways, highlighting their roles in identifying and responding to pathogens.

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Twinkle Tiwana
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3 views

Complement

The complement system consists of approximately 30 soluble proteins that are crucial for the innate immune response, activated through classical, alternative, and lectin pathways. Each pathway leads to the formation of a membrane attack complex that lyses target cells. The document details the mechanisms of activation and regulation of these pathways, highlighting their roles in identifying and responding to pathogens.

Uploaded by

Twinkle Tiwana
Copyright
© © All Rights Reserved
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
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COMPLEMENT

SYSTEM
• TEACHER MICHELLE
SUBMITTED Submitted by
TO Twinkle
NEETU M.SC. Biotech(1)
MAM 248346
COMPLEMENT SYSTEM
 It is known to be comprised of around 30 soluble proteins, together which
constitute around 10% of total serum proteins.
 Most of these proteins are synthesized by liver and remain in inactive form in
the absence of infection.
Complement system is the major component of innate system which is
encountered by pathogens that enter our body after breaching physical barriers
and antimicrobial defenses.
 It consists of three different pathways i.e. classical pathway, alternative
pathway and lectin pathway. All these pathways ultimately lead to a common
terminal pathway, leading to formation of membrane attack complex which
subsequently lyses the target cell.
CLASSICAL PATHWAY

• The classical pathway of complement activation starts when the


complement C1 recognizes a microbial surface directly or indirectly
via antibody bound to pathogen.
ALTERNATIVE PATHWAY
Alternative pathway is antibody-independent, innate immune system component. It is
activated by foreign cell surface and does not require antibody to initiate. In alternative
pathway, serum C3, containing an unstable thioester bond, undergoes slow, spontaneous
hydrolysis to generate C3a and C3b.
The C3b component cannot differentiate host surface from foreign surface but because of
high sialic acid present on host surface, it rapidly deactivates and does not lead to further
cascade. Whereas, on foreign surfaces such as bacteria, yeast and virus; low sialic acid is
present and thus C3b remains active.
C3b then binds factor B by a Mg2+ dependent bond which provides a surface for serum
protein D to bind. Factor D cleaves factor B, releasing Ba. Remaining complex C3bBb
possesses C3 convertase activity but it is very unstable. Another factor, properdin stabilizes
this complex.
The C3 convertase further activates C3 to generate more C3b leading to formation of C5
convertase, C3bBb3b. The C5 is cleaved by C5 convertase to C5a that diffuses away and
C5b, which binds to C6 and starts the membrane attack complex formation
Overview of the complement activation by alternative
pathway, leading to formation of C5b, which eventually leads
to formation of membrane attack complex.
(A) Self and slow activation of small amount of C3 results in
C3b formation that binds on microbial surface.
(B) Factor B is cleaved to Bb and Ba in the presence of factor
D. Bb binds with C3b to form c3 convertase.
(C) Properdin stabilizes the C3bBb i.e. C3 convertase.
(D) C3 is cleaved by C3 convertase, resulting in formation of
C5 convertase (C3bBb3b)
(E) C5 convertase cleaves C5 to C5b and C5a.
Further, C5b participates in membrane attack complex
formation by terminal pathway
LECTIN
PATHWAY
Lectin pathway is also antibody-independent, innate
immune system component.
Lectins are the proteins that bind to carbohydrates. This
pathway initiates with binding of mannose binding lectin
(MBL) to mannose residues on surface of microorganisms.

MBL is an acute phase protein, analogous to C1q of


classical pathway. MBL binding leads to binding of MBL-
associated serine protease (MASP) which further cleaves
and activates C4.
MASP is structurally similar to C1r and C1s.

Rest of the mechanism is similar to classical pathway for


generating C3- and C5-convertase leading to membrane
attack complex formation
Overview of the complement activation by
lectin pathway, leading to formation of C5b,
which eventually leads to formation of
membrane attack complex.

(A)Mannose binding lectin (MBL) binds to


mannose present on microbial surface.

(B) Activation of MBL associated serine


protease (MASP) takes place.
(C) to (F) MBL activated MASP acts like
C1qr2s2 of classical pathway and rest all the
steps are like classical pathway only.
TERMINAL
PATHWAY
C5 convertase upon activation in all the three pathways, cleaves C5 into C5a
and C5b. C5a diffuses away whereas C5b binds to the target surface. C5b
being very labile, is stabilized by C6. Upon binding of C7, C5b67 complex
undergoes hydrophilic-amphiphilic structural transition exposing
hydrophobic regions that serve as binding sites for membrane phospholipids.
If this reaction takes place on target cell surface, C5b67 inserts into
phospholopid bilayer.

Whereas, if it occurs on immune complexes, then the released C5b67


complex enters into membrane of nearby cells causing „Innocent Bystander
Lysis‟, an autoimmune damage. Next C8 binds to C5b67, which creates a
small pore of 10Å. 10-17 molecules of C9 polymerize around C5b678
complexand increase the pore size from 10Å to 70-100Å. This pore causes
osmotic instability in the target cell because of water influx and loss of
electrolytes, ultimately leading to cell lysis
REGUL ATORY
SYSTEM
THANKS

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