CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS Department of Systems Biology Technical University of...

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Department of Systems Biology

Technical University of Denmark

Immunological Bioinformatics

Introduction tothe immune system

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Vaccination

• Vaccination

• Administration of a substance to a person with the purpose of preventing a disease

• Traditionally composed of a killed or weakened micro organism

• Vaccination works by creating a type of immune response that enables the memory cells to later respond to a similar organism before it can cause disease

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Figure 1-20

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Effectiveness of vaccines

1958 start of small pox eradication program

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The Immune System

The innate immune system

The adaptive immune system

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The innate immune system

• Unspecific• Antigen independent• Immediate response• No training/selection hence no memory• Pathogen independent (but response

might be pathogen type dependent)

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The adaptive immune system

Pathogen specific

– Humoral

– Cellular

http://www.uni-heidelberg.de/zentral/ztl/grafiken_bilder/bilder/e-coli.jpg

Bacteria

http://en.wikipedia.org/wiki/Image:Aids_virus.jpg

Virus

http://tpeeaupotable.ifrance.com/ma%20photo/bilharzoze.jpg

Parasite

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Adaptive immune response

Signal induced– Pathogens

• Antigens– Epitopes

B Cell

T Cell

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Antibody - Antigen interaction

Fab

Antigen

Epitope

Paratope

Antibody

The antibody recognizes structural properties of the surface of the antigen

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Technical University of DenmarkCartoon by Eric Reits

Humoral immunity

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The immune response

starts with an antigen

approaching a cell of

the immune system,

here a macrophage.

antigen

macrophage

http://www.pfizerlearninglab.co.uk/

The Humoral Response - Activation Phase

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The macrophage

engulfs the antigen

by phagocytosis.

Lysosome containing enzymes

Antigen engulfed in vesicle


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The vesicle containing an

antigen fuses with a lysosome.

The enzymes in the lysozome

break down the antigen into

fragments. This is antigen

processing.

antigen processing


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Inside the macrophage, the processed

antigens combine with special

class II MHC proteins. These

proteins can move to the cell surface

membrane.

enzymes andproteins combining

Class IIMHC proteins


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The antigen/MHC protein complex is

displayed on the immune cell surface

membrane. The macrophage is now known

as an antigen presenting cell.

Processed antigen/MHC protein complex

Antigen-presenting cell


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The next stage involves a helper T cell (also know as a T-helper

cell) as well as the macrophage

T helper cell (TH)

macrophage (antigen-presenting cell)

receptors which bind to specificantigen/MHC protein complex


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The receptors on the helper T cell enable it to bind to the specific

antigen-MHC complex of the antigen presenting cell.

macrophage (antigen-presenting cell)

helper T cell


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The binding of the helper T cell with the antigen - MHC protein complex triggers the

macrophage to release proteins (cytokines) that activate the helper T cell.

Cytokines from macrophage


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The activated helper T cell now releases its own cytokines

Cytokines from helper T cell


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The released cytokines stimulate the helper T cell to reproduce and

form a clone of cells. Each new cell has the same receptors as the

original helper T cell, so they are specific for the original antigen.

Clone of helper T cells


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Another phase of the immune

response begins with a B cell.

The B cell has membrane

bound globular receptor

proteins (called IgM). Some of

these are specific for the same

antigen presented earlier by the

antigen presenting cell.

antigen

B cell

IgM receptor


The Humoral Response - Effector Phase

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The B cell’s receptor

protein (an IgM)

binds to the antigen,

and the cell engulfs

the antigen by

endocytosis.

IgM bound to antigen engulfed by cell

lysosome


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The vesicle formed

inside the B cell fuses

with a lysosome. This

contains digestive

enzymes which break

down the antigen.

Fused vesicles containing antigen and enzymes from lysosome

B cell


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Fragments of the

digested antigen

remain after

processing within

the vesicle.

Processed antigen

Class IIMHCprotein


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The processed

antigen is attached to

Class II MHC receptors

within the B cell, and

is transported to the

membrane.


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The MHC proteins form a

complex with the

antigen which is

displayed on the surface

of the B cell. It has

become another type of

antigen presenting cell

Antigen/MHC protein complex

B cell (antigen presenting cell)


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A helper T cell from the clone of cells produced earlier specifically recognises the antigen presented by the B cell.

Antigen-presenting B cell

Helper T cell clone


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The helper T cell cell binds to the antigen/MHC

protein complex displayed by the B cell.

This triggers the release of cytokines from the T cell.

Once the cytokines are released the helper T cell no

longer binds to the B cell.

Cytokines released by helper T cell

helper T cell binds to antigen complex on B cell


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The cytokines released by the helper

T cell stimulate the B cell to divide

and form a clone of identical cells

B cell clones


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The B cells continue to divide and form

two groups of clones. Some are long –

lived MEMORY cells. Most are antibody-

secreting PLASMA cells. Plasma cells

have extensive endoplasmic reticulum

and many ribosomes.

Memorycell

Plasma cells


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Plasma cells are essentially antibody factories. They produce and secrete antibodies identical to those of the surface receptors of the original parent B cell

antibodies


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Like the IgM surface receptors on the parent B cell,

the antibodies can bind to and inactivate the

antigens, forming an antibody-antigen complex.

This complex makes it easier for other white blood

cells to engulf the antigen (phagocytosis).

Antibody-antigen complex


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Cellular Immunity

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Diversity is a hallmark of the (adaptive) immune system

Diversity of lymphocytes– Huge diversity within a host– At least 108 different T & B cell clones

Receptors made by recombination & N-additions

Somatic mutation during immune response

Repertoires are (partly) random– Randomness requires self tolerance

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MHC-I molecules present peptides on the surface of most cells

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CTL response

Healthy cell

Virus-infectedcell

MHC-I

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Anchor positions

MHC class I with peptide

CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS Department of Systems Biology Technical University of...

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