Download Immunol-mol-med-3

Immunol mol med 2
Conleth Feighery
2010
This lecture …..
• Importance of lymphocytes in immune
system
• Identification of T and B cells
• How these cells bind antigen - receptors
• How cells become activated
• The involvement of MHC molecules in T
cell function
Medical journals
• It is never too early to start …. dipping into
journals
2 you might consider • New England Journal of Medicine
• Lancet
Major cells of the immune
system
lymphocytes
monocyte
T cell
neutrophil
B cell
dendritic cell
2 types of lymphocytes
T
B
Mature in thymus - regulate, kill
Mature in the bursa - antibody
Neutrophils
ingest foreign material
digest it
“phagocytosis”
• Neutrophils most numerous white cell in circulation
• Short lived - 1 day
• Non-specific
Monocytes
monocyte
Macrophage in tissue
“present” antigen
Phagocytic cells
5 % of circulating cells
Macrophage
Dendritic cells
Major antigen presenting cell in tissues
Ingested antigen is
presented
T cell
B cell
- help
- suppress
- kill
antibody
Monocytes / macrophages
Ingested antigen is
presented
T cell
B cell
- help
- suppress
- kill
antibody
Antigen presenting cells - APC
• Dendritic cells
• Macrophages
• B cells
B cell identification
B cells have a specific receptor
for antigen
antibody molecule
B cell identification
B cells have a specific receptor
for antigen
antibody receptor
binds antigen directly
T cell identification
T cells have a specific receptor
for antigen
TCR = T cell receptor
CD3 on T cells
CD3 molecule bound to TCR
CD3 signals to cell interior
T cell receptor - 2 chains
alpha chain
beta chain
TCR - alpha, beta chains
constant region
variable region
alpha chain
beta chain
variable region
TCR - alpha, beta chains
constant region
variable region
variable region
The shape of the variable
region binds to shape of
different antigens.
B cell receptor
constant
Variable region
Variable region
The shape of the variable
region binds to shape of
different antigens.
T helper cells CD4+ T cells
CD4 molecules on T helper cells
T cytotoxic cells CD8+ T cells
CD8 molecules on T cytotoxic cells
T cell molecules
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T cell receptor = TCR
CD3 - signaling molecule
CD4 - on T helper cells
CD8 - on T cytotoxic cells
• “CD” = cluster of differentiation - used in
describing many molecules of immune
system
For T cells to function ….
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•
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Need TCR - binds antigen
Need CD3 - signals binding via TCR
Need antigen to be “presented” APC
Antigen has to be bound to “MHC” mols.
MHC molecules
Major Histocompatability Complex = MHC
• 2 types
• MHC class I
• MHC class II
• Enable T cells to react with antigen
• MHC = transplantation antigens - also
called HLA molecules = human leucocyte
antigens
CD8+ T cells - MHC I
interaction
CD8
T cytx
TARGET
APC
CELL
CD8+ T cells interact with antigen bound to MHC class I
The CD8 molecule binds exclusively to MHC class I
MHC class I
• Found on all cells in the body
• Essential for function of T cytotoxic cells
• Viral peptides bind to MHC I
Top end of a MHC class I molecule
Don Wiley, died 2001
Scientist,
crystallographer
I'm sorry, but I just don't understand anything in biology
unless I know what it looks like.'
Don Wiley - appreciation
"Wiley was a crystallographer: this is the ultimate
molecular biology. ...The image of a class I MHC
protein with its peptide cargo firmly in place will
stand as a landmark Wiley discovery that forever
changed the field of immunology.…”
MHC class I on target cell
peptide
TARGET
APC
CELL
MHC I molecule
CD4+ T cells - MHC II
interaction
CD4
APC
Th
MHC II
with peptide
CD4+ T cells - MHC II
interaction
CD4
Th
APC
CD4+ T cells interact with antigen bound to MHC
class II molecules
MHC class II
Found on few cells in body • Macrophages
• Dendritic cells
• B cells
All these cells present antigen = antigen
presenting cells or APC
MHC class II on APC
APC
MHC II
with peptide
MHC class II on B cells
B
MHC II
with peptide
antibody
B cells act as APC
Th
B
antibody
T cell stimulation
• T cells bind to antigen and MHC
• Need to bind to a second molecule for full
stimulation
CD4+ T cells - activation
requires 2 signals
CD4
APC
Th
CD28
B7
T cell receptor binding to antigen = signal 1
CD28 binds to B7 = signal 2
Activation of T cells
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Requires 2 signals
Signal 1 - TCR, MHC, antigen
Signal 2 - CD28 binding to B7
Both signals must be from the same APC
ONLY now can T cell proliferation start
CD8+ T cells can kill target cells by inserting a
‘perforating hole’ in the cell, through which enzymes
enter, damaging the cell
CD8
TARGET
APC
CELL
T cytx
• perforin
• enzymes
CD4+ T cells - MHC II
interaction
CD4
APC
Th
CD28
B7
cytokines
CD4+ T cells interact with APC and other cells by
releasing cytokines. APC also release cytokines.
CD4
APC
Th
CD28
B7
cytokines
The type of cytokines that are released are crucial to the
type of immune response which results
Structure of molecules of IS
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T cell receptor
MHC class I
MHC class II
Antibody molecules
Knowledge of these structures helps
understand how the immune system works !