The Complement System(CP)

Noman RezaMasters StudentEhime University

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

Immune System of fish• Specific immune system•Non specific immune system

• Very important in fish• Logical due to aquatic environment

Todays topic

DefinitionThe 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 proteinsThese are mainly made continuously by the liver and

are remain inactive until an infection or another trigger activates them.

Overview Of Complement Protein•Complement protein acts by three ways-•Opsonization :

CP Attach with pathogenMacrophage has special receptor to bind with CPSo macrophage can easily engulf the pathogen

•Membrane attack complex(MAC)CP can break the membrane of the pathogenInrushing the body fluid of pathogenLysis as well as destroy of pathogen

• Enhance inflammation

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

Now the Question is -•How different complement proteins activate through

different pathways?• How the complement proteins act against different

pathogen?

Activation of CP

• These proteins are first to be discovered

Enhance inflammation Cell Lysis,MAC Opsonization

AlternativeC3,Factor

D,B,Propardin

ClassicalC1qrs,C2,C4

LectinMBL/Ficoln,MASP-

2,C4-C2

C3

C3a C3b

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.

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.

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.

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.

Inactive CP to C3 Convertase

A view of different pathways

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

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

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)

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.

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

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

Some Features of Complement Proteins• Complement components shows highest activities at 15-

25º C• Retains activity even at 0-4 0 C• These are inactivated their activity at 45-54 0C• 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)

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 groupChanges in the number of different complement protein.How fast different complement protein number start to

change after pathogen invasion.

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