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Complement_system

The complement system is a crucial component of innate immunity, consisting of over 20 plasma proteins that enhance the ability of antibodies and phagocytic cells to eliminate pathogens. It can be activated through three pathways: classical, alternative, and lectin, each leading to a common terminal pathway that results in opsonization, inflammation, and cell lysis. The main functions of the complement system include opsonization, chemotaxis, cell lysis, and agglutination of pathogens.

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3 views

Complement_system

The complement system is a crucial component of innate immunity, consisting of over 20 plasma proteins that enhance the ability of antibodies and phagocytic cells to eliminate pathogens. It can be activated through three pathways: classical, alternative, and lectin, each leading to a common terminal pathway that results in opsonization, inflammation, and cell lysis. The main functions of the complement system include opsonization, chemotaxis, cell lysis, and agglutination of pathogens.

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noureldintamereisa2004
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Dr/Sarah Samy

Lecturer of
Microbiology&Immunology
Faculty of Medicine
Suez University

Complement system
INTRODUCTION
• Complement is a central part of the innate immunity that
serves as a first line of defense against foreign and altered host
cells.

• The complement system helps or “complements” the ability of


antibodies and phagocytic cells to clear pathogens from an
organism.

• The complement system is composed of plasma proteins


produced mainly by the liver or membrane proteins expressed
on cell surface
• The complement system refers to a series of >20proteins,
circulating in the blood and tissue fluids. Most of the
proteins are normally inactive, but in response to the
recognition of molecular components of microorganisms
they become sequentially activated in an enzyme cascade

• Complement proteins collaborate as a cascade to opsonize


pathogens and induce a series of inflammatory responses
helping immune cells to fight infection and maintain
homeostasis

• The complement system can be initiated depending on the


context by three distinct pathways – classical (CP), lectin
(LP), and alternative (AP), each leading to a common
terminal pathway.
Classical Pathway

• This pathway involves complement components C1, C2 and C4.

• The pathway is triggered by antibody(either IgM or IgG) antigen


complexes binding to C1, which itself has three subcomponents C1q,
C1r and C1s.

• C1 is actually a complex that consists of three different types of subunits


- the C1q, C1r and C1s. The antibody that is bound to the antigen binds
onto the C1q region of the C1 protein complex and that activates the
C1r and C1s regions.

• The C1s protein is a serine protease and can go on to cleave and activate
the C2 and C4 complement proteins

• . C2 is broken down into C2a and C2b while C4 is broken down into C4a
and C4b.

• C2b diffuses into the plasma as a protein inflammatory mediator while


C2a remains attached with C4b, forming the C3-convertase (C4b2a).

• This complex, also known as C3 convertase, goes on to cleave and


activate yet another complement protein called C3. C3 is broken down
• the large fragment, C3b, can covalently
attach to the surface of microbial
pathogens and opsonise them;
•
• The small fragment, C3a, activates mast
cells, causing the release of vasoactive
mediators such as histamine.

• Some of the C3b binds to C4b2a to form


a trimolecular complex C4b2a3b called
C5 convertase. The C5 convertase splits
C5 into C5a and C5b. C5a diffuses away,
while C5b attaches to C6 and initiates
formation of C5b–9 complex otherwise
known as membrane attack complex
(MAC).
The Alternative Pathway
• Unlike the classical pathway, the
alternative pathway is triggered when
the C3b protein directly binds a
microbe. It does not require the
presence of antibody-antigen
complexes to activate itself .

This is because one of the major proteins of the


complement system, the C3 protein, can activate
itself spontaneously via a hydrolysis process.
Under normal conditions (in the absence of
pathogenic agents), the spontaneous breakdown
of C3 into C3a and C3b is not a problem because
our healthy cells contain an inhibitory protein on
their membrane that can quickly bind C3b and
inactivate it <not from memorization>χχ
• It can also be triggered by foreign materials and damaged tissues..
For example microbial inflammatory mediators e,
lipopolysaccharide, the toxin of gram-negative bacteria, may
activate this pathway.

• This pathway involves various factors, B, D, H & I, which interact with


each other, and with C3b, to form a C3 convertase, C3bBb

• The pathogenic antigen (such as LPS) activates C3 so it creates a C3b


complex

• Factor D cleaves the C3B complex so that C3bBb is created.

• C3bBb is a C3 convertase, which converts more C3 into C3a and C3b.

• When a second C3b adds to it, it will form the C3b-Bb-C3b complex,
called C5 convertase
•
Lectin Pathway
• lectin pathway is identical to the Classical pathway (CP)
except for the components involved in the initiation of the
complement cascade. Instead of a C1q/C1 complex the LP
initiation is done by the binding of mannose-binding lectin
(MBL) to mannose residues on the pathogen surface.

• This pathway is activated by the binding of mannose-


binding lectin (MBL) to mannose residues on the pathogen
surface.

• This in turn activates the MBL-associated serine proteases,


which activate C4 and C2, to form the C3 convertase,
C4b2a.

• Functionally, C4b and C2b forms the C3 convertase (C4b2a)


identical to the one formed in the CP. The C3 convertase
later joins with C3b to make the C5 convertase (C4b2a3b)..
Lytic Pathway
• This pathway is initiated by the
splitting of C5, and attachment of C5b
to a target.

• C6, C7, C8 and C9 unite with C5b,


and this membrane-attack complex
(MAC), when inserted into the outer
membrane of some bacteria, can
contribute to their death by lysis.

•
• . Membrane Attack Complex (MAC) is
the terminal complex of the
complement system of the innate
immune system
Main functions of the Complement System

1. Opsonization: Increases phagocytosis by opsonins (C4b and


C3b) binding to foreign organisms .
2. Chemotaxis: Attracts macrophages and neutrophils via
inflammation by inflammatory mediators; C5a, and to a
lesser extent C3a and C4a
3. Cell lysis: Ruptures membranes due to formation of a
membrane attack complex (MAC)
4. Agglutination: Causes clustering and binding of pathogens
REFERNCES
• https://
www.frontiersin.org/articles/10.3389/fimmu.2015.00262/full
• https://
www.immunology.org/public-information/bitesized-immunolo
gy/systems-and-processes/complement-system

• https://microbenotes.com/lectin-pathway-complement-syste
m
/

• https://www.svarlifescience.com/knowledge/focus-areas/
complement-system-overview

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