Immunol mol med 2 Conleth Feighery 2010. This lecture ….. Importance of lymphocytes in immune...
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Transcript of Immunol mol med 2 Conleth Feighery 2010. This lecture ….. Importance of lymphocytes in immune...
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Immunol mol med 2
Conleth Feighery
2010
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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
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Medical journals
• It is never too early to start …. dipping into journals
2 you might consider -
• New England Journal of Medicine
• Lancet
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Major cells of the immune system
T cell
B cell
lymphocytes
neutrophil
monocyte
dendritic cell
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2 types of lymphocytes
T
B
Mature in thymus - regulate, kill
Mature in the bursa - antibody
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Neutrophils
ingest foreign materialdigest it
“phagocytosis”
• Neutrophils most numerous white cell in circulation
• Short lived - 1 day
• Non-specific
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Monocytes
Macrophage in tissue“present” antigen
monocyte
Phagocytic cells5 % of circulating cells
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Macrophage
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Dendritic cells
T cell- help- suppress- kill
B cell
antibodyIngested antigen is
presented
Major antigen presenting cell in tissues
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Monocytes / macrophages
T cell- help- suppress- kill
B cell
antibodyIngested antigen is
presented
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Antigen presenting cells - APC
• Dendritic cells
• Macrophages
• B cells
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B cell identification
B cells have a specific receptor
for antigen
antibody molecule
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B cell identification
B cells have a specific receptor
for antigen
antibody receptorbinds antigen directly
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T cell identification
T cells have a specific receptorfor antigen
TCR = T cell receptor
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CD3 on T cells
CD3 molecule bound to TCR
CD3 signals to cell interior
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T cell receptor - 2 chains
alpha chain
beta chain
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TCR - alpha, beta chains
alpha chain
beta chain
variable region
variable region
constant region
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TCR - alpha, beta chains
The shape of the variable region binds to shape of different antigens.
variable region
variable region
constant region
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B cell receptor
The shape of the variable region binds to shape of different antigens.
Variable region
Variable region
constant
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T helper cells -CD4+ T cells
CD4 molecules on T helper cells
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T cytotoxic cells -CD8+ T cells
CD8 molecules on T cytotoxic cells
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T cell molecules
• 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
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For T cells to function ….
• Need TCR - binds antigen
• Need CD3 - signals binding via TCR
• Need antigen to be “presented” APC
• Antigen has to be bound to “MHC” mols.
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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
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CD8+ T cells - MHC I interaction
APCT cytxTARGET
CELL
CD8
CD8+ T cells interact with antigen bound to MHC class IThe CD8 molecule binds exclusively to MHC class I
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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
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Don Wiley, died 2001
I'm sorry, but I just don't understand anything in biology unless I know what it looks like.'
Scientist, crystallographer
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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.…”
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MHC class I on target cell
APC
MHC I molecule
TARGETCELL
peptide
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CD4+ T cells - MHC II interaction
APC
MHC IIwith peptide
T h
CD4
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CD4+ T cells - MHC II interaction
APCT h
CD4
CD4+ T cells interact with antigen bound to MHC class II molecules
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MHC class II
Found on few cells in body -
• Macrophages
• Dendritic cells
• B cells
All these cells present antigen = antigen presenting cells or APC
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MHC class II on APC
APC
MHC IIwith peptide
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MHC class II on B cells
MHC IIwith peptide
B
antibody
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B cells act as APC
T h B
antibody
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T cell stimulation
• T cells bind to antigen and MHC
• Need to bind to a second molecule for full stimulation
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CD4+ T cells - activation requires 2 signals
APCT h
CD4
T cell receptor binding to antigen = signal 1
CD28 B7
CD28 binds to B7 = signal 2
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Activation of T cells
• 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
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CD8+ T cells can kill target cells by inserting a ‘perforating hole’ in the cell, through which enzymes enter, damaging the cell
APCT cytxTARGET
CELL
CD8
• perforin• enzymes
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CD4+ T cells - MHC II interaction
cytokines
APCT h
CD4
CD28 B7
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CD4+ T cells interact with APC and other cells by releasing cytokines. APC also release cytokines.
cytokines
The type of cytokines that are released are crucial to the type of immune response which results
APCT h
CD4
CD28 B7
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Structure of molecules of IS
• T cell receptor
• MHC class I
• MHC class II
• Antibody molecules
Knowledge of these structures helps understand how the immune system works !