Innate immune system is very important in case of fish. Complement system is the part of innate immune system. In this presentation there is a overview of the complement system.

1. The Complement
System(CP)
Noman Reza
Masters Student
Ehime University

2. Outline
• Immunity system of fish
• Definition
• Overview of CP
• Activation Of CP
• CP way of work
• Why not act against host cell
• Deactivation of complement protein
• Some Features of Complement Proteins
• CP of Fish

3. Immune System of fish
• Specific immune system
• Non specific immune system
• Very important in fish
• Logical due to aquatic environment

6. Todays topic

7. Definition
The blood and other extracellular fluids contain
numerous proteins with antimicrobial activity, some of
which are produced in response to an infection. The
most important of these are components of the
complement system.
The complement system is a part of the immune
system that enhances (complements) the ability of
antibodies and phagocytic cells to clear pathogens from
an organism.
It is now known that it consists of over 30 proteins
These are mainly made continuously by the liver and
are remain inactive until an infection or another trigger
activates them.

8. Overview Of Complement
Protein
•Complement protein acts by three ways-
• Opsonization :
CP Attach with pathogen
Macrophage has special receptor to bind with CP
So macrophage can easily engulf the pathogen
• Membrane attack complex(MAC)
CP can break the membrane of the pathogen
Inrushing the body fluid of pathogen
Lysis as well as destroy of pathogen
• Enhance inflammation

9. Overview Of Complement
Protein
• Three distinct pathways of
complement activation—the
classical pathway, the lectin
pathway, and the alternative
pathway.
• The early components of all
three pathways activate C3.C3
is very important components.
The deficiency of C3 indicates
the repeated bacterial infection.
• On Complement system,
activation of one CP help
another CP to activate. In these
way almost all CP are activated
on the Infected place. These
process is called Cascade system
Ovarview of Cascade system

10. Now the Question is -
• How different complement proteins activate through
different pathways?
• How the complement proteins act against different
pathogen?

11. Activation of CP
• These proteins are first to be discovered
Enhance inflammation Cell Lysis,MAC
Opsonization
Alternative
C3,Factor
D,B,Propardin
Classical
C1qrs,C2,C4
Lectin
MBL/Ficoln,MASP-
2,C4-C2
C3
C3a C3b

12. Activation of CP
• After Pathogen insert into the body, antibody bound to
the surface of the pathogen thus activate the classical
pathway.
• Recognition of fungal glycolipids and glycoproteins
bearing terminal mannose activate the lectin pathway
• These two pathway cause the activation of
Complement component C3(C3a,C3b) and with the help
of these C3, alternative pathway activate.

13. CP activation on Classical
Pathway
• Classical Pathway : Its
activated when
antigen/pathogen insert into
the body and antibody bind
with it. Then CP C1qrs
attached with it make
protein complex C4b2a
that’s called C3 convertase.
• C4b2a/C3 convertase is on
the surface of pathogen that
activate the C3 that means
production of C3a and C3b.

14. CP activation on Lectin
Pathway
• Lectin pathway: Ficolin
bind with
oligosaccharide ,MBL
bind with mannose and
produce protein
complex C4b2a or C3
convertase
• C4b2a/C3 convertase is
on the surface of
pathogen that activate
the C3 that means
production of C3a and
C3b.

15. CP activation on Alternative
Pathway
• Activation of C3 on Classical and Lectin pathway produce lots of
C3a and C3b.
• These C3b binds to the pathogen and with the help of factor D and
B it produces another complex C3bBb that’s also called C3
convertase.
• Also on lectin pathway, activate C3b with another protein
Properdin produce C3 convertase C3bBb
• C3bBb/C3 convertase is on the surface of pathogen that activate
the C3 that means production of C3a and C3b.

16. Inactive CP to C3 Convertase

17. A view of different pathways

19. C3a way of work
• C3a(Enhance
inflammation):Activate C3a
bind with C5a and stimulate the
production of mast cell which
secret the histamine
• Histamine-Enhance
inflammation, Attract
leucocytes

20. C3b way of work
• C3b:
• Opsonization
• Membrane Attack Complex(MAC)
Opsonization:
 C3b can do thioester bond. With
this bond C3b bind with pathogen.
• On the other way Macrophage has
two receptor CR1 and C5a receptor.
For binding with pathogen it needs
CP C5a.CP C5a bind with C5a
receptor and allows CR1 to bind with
C3b which attached with pathogen.
• This way Macrophage can perform
phagocytosis by eating up the
pathogen

21. Activation of C5-C5a,C5b
• So how C5 is activated?
• C3b can bind with the C3 convertase(C4b2a, C3bBb) and can
produce 2 proteins.
• C3(C3a,C3b)
• C5(C5a,C5b)

22. Membrane attack
complex(MAC)
• C5a help in enhance inflammation, Opsonization
• C5b with other higher CP like C7,C8,C9 format the MAC
.Formation of MAC can break the cell membrane of
pathogen ,inrushing the body fluid of pathogen as well as
lysis of pathogen.

23. Why not act against Host
cell
• Host cells have various plasma membrane molecules that
prevent complement reactions from proceeding against
their cell.
• Among these molecules most important is Sialic
acids(carbohydrate moieties).
• Generally pathogen are lack of these sialic acid

24. Deactivation of Complement
Protein
• There are two ways of CP deactivation-
• Specific inhibitor proteins in the host cell terminate the
cascade after completing work
• Many protein are unstable,unless they bind immediately
to either the next component in the complement, so
without pathogen activity they rapidly inactivate

25. Some Features of Complement
Proteins
• Complement components shows highest activities at 15-
25º C
• Retains activity even at 0-40
C
• These are inactivated their activity at 45-540
C
• Fish complement system display bactericidal activity
against non-virulent strains of gram negative bacteria.
• Typically CP has C Infront of each(C1,C2,C3..)
• They are tend to be activated when they are cleaved by
something.(Ex-C3-C3a,C3b.C5-C5a,C5b)

26. Study of CP in fish
• The most important Complement protein is C3 that’s mean
C3a and C3b.These protein with other CP do enhance
inflammation, opsonization and MAC. So Increasing number
of these protein on blood serum indicates some pathogen
on fish body. Also decreasing number indicates the innate
immune deficiency of the fish. As for example the deficiency
of C3 indicates the repeated bacterial infection. So
• By comparing between two group fish(1.before pathogen
infection,2after pathogen infection)
Different complement protein content in both group
Changes in the number of different complement protein.
How fast different complement protein number start to
change after pathogen invasion.

27. Thank You