complement system - ruhr university bochum · janeways’ immunobiology 9th edition, garland...

Presented by Innas SultanaMolecular Immunology Seminar

Date: 15.05.2019

Complement SystemActivation of Membrane attacking complex (Mac), Role of Complement

Receptors and Role of small fragments of complement proteins

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CONTENT

Introduction

Overview of Complement pathways

C3-the key component of complement system

Activation of Membrane attacking complex (MAC) and its effects

Complement receptors (CRs)

Small fragments of Complement proteins (C3a, C4a, C5a)

Multiple activities of Complement system

Summary

2 Activation of MAC, Role of Complement Receptors and Small frgaments| Innas Sultana |15.05.2019| Molecular Immunology Seminar

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Introduction

The term “complement” refers to a system of factors present in the

normal serum activated in the presence of pathogens

mediate a number of biologically significant consequences

Discovered in1890s by Jules Bordet as a heat-labile substance in normal plasma

Major component of innate immunity

Composed of more than 30 different plasma proteins, produced mainly by liver

3 major pathways: 1) Classical 2)Alternative 3) Lectin

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Activation of MAC, Role of Complement Receptors and Small frgaments| Innas Sultana|15.05.2019| Molecular Immunology Seminar

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Overview of Complement pathways

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Figure:

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Activation of MAC, Role of Complement Receptors and Small frgaments| Innas Sultana |15.05.2019| Molecular Immunology Seminar

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C3- the key component of complement system

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C3 C3a + C3b

C3

convertase

Local

inflammatory

response

Up to 1000 molecules of C3b bind

covalently on the pathogen surface in

the vicinity of single active C3

convertase

Deposition of large

quantities of C3b on the

pathogen surface

Destruction of pathogen by

phagocytosis/ Lysis of

cells by MAC formation

Most abundant

complement protein

in plasma

Conc: 1.2 mg/ml of

plasma

Destruction of

pathogens


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Formation of C5 convertase

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1

• Binding of C3b to C3 convertase to form C5 convertase

2

• Binding of C5 to the C5 convertase enzyme

3

• Cleavage of C5 into C5a and C5b by C5 convertase

Figure 2.25

Immunobiology,

9/e (Garland

Science 2012)

C5b

C5a

C5


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Activation of Membrane attacking complex (MAC)

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Figure 2.31 Immunobiology,9/e (Garland Science 2012)

MAC pore

C5b

C6

C7

C5b67

complex

C8 C9


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Effects of Membrane attacking complex on target cells

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Figure 2.31 Immunobiology,9/e (Garland

Science 2012)


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Complement Receptors (CRs)

Receptors Cell types Binding

specificity

Functions

CR1 Erythrocytes, macrophages,

monocytes, B cells, FDC,

polymorphonuclear

leukocytes

C3b, C4bi Stimulates phagocytosis,

promotes C3b and C4b

decay

CR2 B cells, FDC iC3b,

C3d, C3dg,

Epstein-Barr

virus

Part of B cell co-receptor,

Epstein bar virus receptor

CR3 Macrophages, monocytes,

FDC, polymorphonuclear

leukocytes

iC3b Stimulates phagocytosis

CR4 Macrophages, monocytes,

FDC, polymorphonuclear

leukocytes

iC3b Stimulates phagocytosis

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Complement Receptors (CRs)

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Receptors Cell types Binding

specificity

Functions

CRIg Macrophages iC3b, C3b Phagocytosis of

circulating pathogens

C3a receptor Endothelial cells,

mast cells, phagocytesC3a Binding of C3a

activates G protein

C5a receptor Endothelial cells,

mast cells, phagocytesC5a Binding of C5a

activates G protein



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Role of Complement Receptor (CR1)

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Stimulation of phagocytosis by CR1 receptors with the help of C5a


PhagosomePhagolysosome


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Role of Complement Receptors (CR2, CR3, CR4)

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Ligand for CR2, CR3,

CR4 and CRIg

receptors present on

phagocytes

C3dg

C3f

Recognized by

CR2 receptors on

B cells


Stimulates

PhagocytosisStimulates antibody

response

iC3b


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Small fragments of complement proteins

C3a, C4a, C5a

C3a, C5a

Act on specific receptors on mast cells and endothelial cells

Produce local inflammatory responses

Often referred to as anaphylatoxins

C5a has highest specific biological activity

C4a

Not potent at inducing inflammation, is inactive at C3a and C5a

receptors, and seems to lack a receptor of its own.


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Role of C5a fragments in phagocytosis

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Enhancement of

phagocytosis by

anaphylatoxin

C5a


C3b

C5a receptor

CR1

C5a


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Effect of C3a, C5a fragments on mast cells

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C3a and C5a bind to mast cells and

causes them to release histamine

and tumor necrosis factor (TNF-α)

Figure:

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Histamine increases permeability

of blood vessel and stimulates

further inflammatory response

Activation of MAC, Role of Complement Receptors and Small frgaments| Innas Sultana|15.05.2019| Molecular Immunology Seminar

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Local inflammatory responses by C3a, C5a fragments

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Figure 2.29 Immunobiology,9/e (Garland

Science 2012)

C3a, C5a act on blood

vessels and increase

vascular permeability

Increased vascular

permeability causes fluid

leakage and recruitment

of antibody, complement

and phagocytic cells to

the site of infection


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Multiple activities of Complement system

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Summary


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Reference

Murphy, K. and Weaver, C. (2012). Janeways’ Immunobiology 9th edition, Garland Science.


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Thank you

for your attention!

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complement system - ruhr university bochum · janeways’ immunobiology 9th edition, garland...

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