immunology 2 nd med 2009 some revision points con feighery
TRANSCRIPT
Lecture content
• How to recognise T cells and B cells• Structure of the T cell receptor• The different types of T cells• The role of MHC in activation of T cells• How cytokines influence the immune system
B cell identification
B cells have a specific receptorfor antigen
antigen can bind directlyto this receptor
TCR - alpha, beta chains
The shape of the variable region binds to the shape of different antigens.
variable region
variable region
constant region
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
For T cells to function ….
• Need TCR - binds antigen• Need CD3 - signals binding• Need antigen to be “presented” APC• Antigen has to be bound to “MHC” mols.• Co-stimulation signal to T cell ….
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
APCT cytxTARGET
CELL
CD8
CD8+ T cells interact with antigen bound to MHC class IThe CD8 molecule binds exclusively to MHC class I
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
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
I'm sorry, but I just don't understand anything in biology unless I know what it looks like.'
Scientist, crystallographer
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.…”
CD4+ T cells - MHC II interaction
APCT h
CD4
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 cellsAll these cells present antigen = antigen
presenting cells or APC
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 !
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 !
Immunoglobulin super-family
Many molecules in the immune system have an Ig-like structure and hence, belong to the “Ig superfamily”.
Alberts et al.
CYTOKINES
Cells of the immune system ‘talk’ to each other by producing cytokines - like
‘text messages’ informing cells what their function should be!
Cytokine product of cells
APCT h
IL-1
IL-2Cells interact through the productionand release of cytokines - these bind to cells and affect their function
CD28 B7
Cytokines
• Small protein molecules c. 20,000 aa• Specific types produced by different cells• Bind to cells and affect cell function• Some are called “interleukins” or IL
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
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
Stimulated T cell - IL-2 produced
APCT h
CD4
CD28 B7
IL-2
IL-2 receptor
IL-2 binds to receptor on cell - causes cell growth, division
CTLA-4 - negative signal
APCT h
CD4
T cell receptor binding to antigen = signal 1
CTLA-4 B7
CTLA-4 binds to B7 - inhibits stimulation
CD4+ T cells interact with APC and other cells by releasing cytokines. APC also release cytokines.
APCT h
cytokines
The type of cytokines that are released are crucial to the type of immune response which results
T cell cytokines affect B cells
T h B
IL-4, IL-5, IL-6
IL-4, 5 and 6 allinvolved in B cellstimulation and Igproduction
Interferon gamma helps kill intracellular infections
MOT h
TB
Interferon - gammaIFN-
IFN- activates macrophage killingmechanisms
Cytotoxic T cells
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
T cytotoxic cell - recognition of antigen, role of CD8
APCT cytx
T cytotoxic cell reacting with virus antigen presented by MHC class I molecule
CD8
MHC I
Target cell
virus
T cytotoxic cell - cytolytic mechanism
APCT cytx
Target cell
virusLytic granules
perforinEnzymes, water, salts
Granules - contentperforin,enzymes
Types of T helper cells
• Cytokine production by T helper cells varies• Effect on the immune system varies• Sub-types of T helper cells• Th1 cells – interferon gamma product• Th2 cells – IL-4, IL-5, IL-6• Th17 cells – IL-17• T regulatory cells – IL-10