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Immunological Bioinformatics
Introduction to
the immune system
Department of Systems Biology
Technical University of Denmark
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
Department of Systems Biology
Technical University of Denmark
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•
Figure 1-20
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Effectiveness of vaccines
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1958 start of small pox
eradication program
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Technical University of Denmark
The Immune System
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The innate immune system
The adaptive immune system
Department of Systems Biology
Technical University of Denmark
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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Technical University of Denmark
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•
•
•
•
•
The adaptive immune system
– Humoral
Parasite
– Cellular
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Virus
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Bacteria
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Technical University of Denmark
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Pathogen specific
Adaptive immune response
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Signal induced
– Pathogens
• Antigens
– Epitopes
B Cell
T Cell
Department of Systems Biology
Technical University of Denmark
Antibody - Antigen interaction
The antibody recognizes
structural properties of the
surface of the antigen
Fab
Epitope
Paratope
Antibody
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Technical University of Denmark
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Antigen
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Humoral immunity
Department of Systems Biology
Cartoon by Eric Reits
Technical University of Denmark
The Humoral Response - Activation
Phase
The immune response
starts with an antigen
approaching a cell of
the immune system,
here a macrophage.
macrophage
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antigen
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Antigen engulfed in vesicle
The macrophage
engulfs the antigen
by phagocytosis.
Lysosome
containing
enzymes
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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.
Class II
MHC proteins
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enzymes and
proteins combining
The antigen/MHC protein complex is displayed on
the immune cell surface membrane. The
macrophage is now known as an antigen
presenting cell.
Antigen-presenting cell
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Processed antigen/
MHC protein complex
The next stage involves a helper T cell (also know as a T-helper cell) as
well as the macrophage
T helper cell (TH)
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macrophage (antigen-presenting cell)
Technical University of Denmark
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receptors which bind to specific
antigen/MHC protein complex
The receptors on the helper T cell enable it to bind to the specific antigenMHC complex of the antigen presenting cell.
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helper T cell
macrophage (antigen-presenting cell)
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Cytokines from
macrophage
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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.
The activated helper T cell now releases its own cytokines
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Cytokines
from helper
T cell
cell, so they are specific for the original antigen.
Clone of helper T cells
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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
The Humoral Response - Effector Phase
IgM). Some of these are specific for
the same antigen presented earlier
by the antigen presenting cell.
IgM receptor
antigen
B cell
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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 bound to
antigen engulfed
by cell
lysosome
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The B cell’s receptor
protein (an IgM) binds to
the antigen, and the cell
engulfs the antigen by
endocytosis.
B cell
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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
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Fragments of the
digested antigen
remain after
processing within the
vesicle.
Processed antigen
Class II
MHC
protein
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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
B cell (antigen presenting cell)
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Antigen/MHC protein complex
A helper T cell from the clone of cells produced earlier specifically
recognises the antigen presented by the B cell.
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Helper T cell clone
Antigen-presenting B cell
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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.
helper T cell binds to
antigen complex on B cell
Cytokines released by
helper T cell
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The helper T cell cell binds to the antigen/MHC protein
complex displayed by the B cell.
B cell clones
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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
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.
Plasma cells
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Memory
cell
antibodies
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Technical University of Denmark
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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
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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Like the IgM surface receptors on the parent B cell, the
antibodies can bind to and inactivate the antigens, forming
Cellular Immunity
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Department of Systems Biology
Technical University of Denmark
Diversity is a hallmark of the
(adaptive) immune system
– Huge diversity within a host
– At least 108 different T & B cell clones
Receptors made by recombination & Nadditions
Somatic mutation during immune response
Repertoires are (partly) random
– Randomness requires self tolerance
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Diversity of lymphocytes
MHC-I molecules present peptides on
the surface of most cells
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CTL response
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Healthy
cell
MHC-I
Virusinfected
cell
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MHC class I with peptide
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Anchor positions
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