Scribd
Upload
4 views

Complement System

The complement system is a crucial part of the immune response, consisting of over 30 serum and cell surface proteins that help defend against pathogens. It operates through three main pathways: classical, alternative, and lectin, each with distinct activation mechanisms and functions such as opsonization, cell lysis, and inflammation. The system enhances the ability of antibodies and phagocytic cells to clear microbes and promote inflammation, ultimately leading to pathogen destruction.

Uploaded by

zulkifalayazllc
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
4 views

Complement System

The complement system is a crucial part of the immune response, consisting of over 30 serum and cell surface proteins that help defend against pathogens. It operates through three main pathways: classical, alternative, and lectin, each with distinct activation mechanisms and functions such as opsonization, cell lysis, and inflammation. The system enhances the ability of antibodies and phagocytic cells to clear microbes and promote inflammation, ultimately leading to pathogen destruction.

Uploaded by

zulkifalayazllc
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
You are on page 1/ 47

COMPLEMENT SYSTEM

DR MUSARRAT
ZAHRA
LEARNING OBJECTIVES
Define complement system
Outline different types of pathways in complement system
Describe the functions of complement system
Functions of membrane attack complex
HISTORY

 Research in complement started in 1890s when Jules
Bordet at the Institut Pasteur of Paris conducted
experiment using sheep antiserum.

 He named those substances as

Alexins.

 Paul Ehrlich coined the

e
tm
r complement.
INTRODUCTION

 It is named “complement system” because it was first
identified as

a heat-labile component of serum that “complemented”


antibodies

in the killing of bacteria.

 Consists of serum and cell surface proteins involved in


defense

against pathogens and tissue damage mediated by antibodies

 The Complement system is the major effector of

humoral branch of immune system.


Functions of the
complement

system
 Opsonisation

 Chemotaxis

 Cell lysis

 Immune clearance

 Activation of inflammatory response


The components of
complement

system
 Over 30 serum and cell surface proteins:
- Complement components

(in serum inactive, activated sequentially as a cascade)


- Complement receptors

(cell surface, recognize activated components)


- Regulatory proteins of complement

(both in serum and cell surface, inhibit activated


components)

Components are designated by numbers (E.g. ; C1 – C9) or


latters (E.g. : Factor D).
 They are mainly synthesized by hepatocytes
 Also produced by blood monocytes, tissue macrophages and
epithelial cells of he gastrointestinal and genitourinary tract.
 Complement proteins: Made as zymogens - activation by
cleavage.

 Exampl C
e: 4

C4 C4
a b

a = smaller b= larger fragment.


fragment Diffusion remains bound to
& signaling microbe

 Exception: C2a = large


C2: fragment C2b =
small fragment
Three pathways for
Complement

activation:
1. Classical Pathway
 2. Alternative Pathway
 3. Lectin or MBL Pathway

 Pathways for activation require multiple


steps categorized as:

 1. Recognition Unique proteins


 2. Enzyme for 1st 2 steps
activation
common
 3. Biological
proteins
THE CLASSICAL PATHWAY

 Part of immune system


 Relies on Ag – Ab complex to get
activated
 The classical pathway is initiated by:

1.Ab binding to the pathogen.

2. C1 proteins binds to the Fc of


Ab.

C1 Protein

C1q- 18 polypeptides
6 arms with globular heads-
Binds Fc on IgG or IgM to get
activated

2 C1r + 2 are activated


C1s
by activated
C1q.
Pathoge Pathoge
n n

Cleavage of C3 reveals a thioester bond


and it will bind to cell surface of
pathogen.
C3
b
C3b is an opsonin
microb
e
Opsonins are molecules
that bind both to
bacteria and
phagocytes

Opsonization
phagocytosis increases
by 1,000
C3b s attached
to microbial fold.
surface
 C4b-2a-3b functions as the
classical C5 convertase:
FORMATION OF MEMBRANE ATTACK COMPLEX

C5
b

Cell
membrane

Pathoge
n
C
6

Cell
membrane

Pathoge
n
C
7

Cell
membrane

Pathoge
n
Cell
membrane
C
8
Cell
membrane

Pathoge
n
C
9
Cell
membrane

Pathoge
n
Cell
membrane

Pathoge
n
Cell
membrane

Pathoge
n
Cell
membrane

Pathoge
n
Cell
membrane

Pathoge
n
Cell
membrane

Pathoge
n
Cell
membrane

Pathoge
n
Functions of C3a
and C5a
Neutrophi
Granules l
containin
g
inflammat
o ry
agents
like
histamine

Macrophag
e

 C3a and C5a increases the inflammatory response by binding to


mast cells and causing them to release histamine.

 Most powerful chemotactic factor known for leukocytes.


The Alternative
Pathway


Also called as Properdin pathway

 Part of innate immunity.

 Antibody Independent.

 The alternative pathway is slower


than h
te Classical pathway.

 Molecules of C3 undergo cleavage at


continuous low level in normal plasma.
Activation of
Alternative
pathway
 C3 contains in unstable
thioester bond.
 This unstable bond
makesC3 subject to slow
spontaneous hydrolysis
to C3b and C3a
 The C3b is able to bind to
foreign surface antigens.
 Mammalian cells contain
sialic acid which
inactivates C3b
Factor
B
 C3b on the surface of
a foreign cells binds
to another plasma
protein called factor
B
 This binding of Factor
B results in the
exposure of a binding
site for another
enzyme called Factor
D
Factor
D
 The binding of factor B
to C3b allows a protein
enzyme called Factor D
to cleave Factor B to Ba
and Bb.
 Factor Bb remains bound
to C3b while Ba and
Factor D disperse away.
 The complex C3bBb
B
is C3 convertase a
of alternative
pathway
Properdin-
Factor P

 Stabilizes C3b-Bb so it may cleave more


C3.
May cleave over a million C3 molecules!
 Protects Bb-C3b from inactivation
by complement control
C5
activation

 C3b-C3b-Bb functions as the C5 convertase in


the alternative pathway.
MAC
formation
Lectin Binding
Pathway



Independent of antibodies.

Lectins are proteins that bind to specific cb


targets.

 Activated by Mannose binding lectin (MBL) –


lectin h
tat binds to mannose residues on the
microbes.

 MBL is similar to C1q in structure and function.


Activation of
lectin
pathway
 First step is binding of Mannose
Binding Lectin (MBL) to mannose
residue on the surface of microbes.
 To the MBL bound to microbe, MBL –
Associated Serine Proteases (MASP – 1
and MASP – 2) will bind.
 MASP 1 and 2 is similar in structure
and function to C1s andC1r
 This complex will cleave C4 and C2
Effector functions of
complement

system
 1. Facilitates Opsonization :
Extremely important when pathogen
carries a
capsule.
2.Cell
lysis
3. Immune complex
clearance
4. Inflammatory response and
chemotaxis
and
C3b
OVERVIEW

You might also like