immunology molecular medicine 3 conleth feighery
TRANSCRIPT
Immunology molecular medicine 3
Conleth Feighery
Learning objectives
• T cell binding to APC essential for T cell stimulation
• T cell cytokines – determine their effect
• APC use pattern recognition receptors
• The structure of the T cell receptor
CYTOKINES
Cells of the immune system ‘talk’ to each other by producing cytokines - like ‘text messages’ informing cells
what their function should be!
CD4+ T cells - MHC II interaction
APCT h
cytokines
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
Cytokine products of cells
APCT h
IL-1IL-2
CD28 B7
Cytokine product of cells
APCT h
IL-1IL-2
Cells interact through the productionand release of cytokines - these bind to cells and affect their function
CD28 B7
Cytokine products of cells
APCT h
IL-1
IL-2 Receptors - cytokines bind to specific cell receptors
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
IL-1 helps T cell activation
APCT h
IL-1 producedby APC
T cell co-stimulation
Essential to T cell activation, division and replication
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
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
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
IL-2 required for T cell growth
APCT h
IL-2
CD28 B7
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
T cell cytokines affect B cells
T h B
IL-4,5,6
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
Lymph node - cartoon
Alberts et al.
T cell activation takes place in lymph node tissueT cell help for B cells takes place in lymph. follicles
Lymph node - histology
Lymphoid follicles
Interferon gamma helps kill intracellular infections
MOT h
TBInterferon - gamma
IFN-
IFN- activates macrophage killingmechanisms
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
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 - cytolytic mechanism
APCT cytxTarget cell
virusLytic granules
perforinEnzymes, water, salts
Granules - contentperforin,enzymes
Pattern recognition receptors
Various stimulibind to receptorson APC and influence APC reaction
APC
TOLL Stimulus
Pattern recognition receptors
Various stimulibind to receptorson APC and influence APC reaction
Different cytokinesAPC
B7
Toll-like receptors
Stimulus
APC –effect on T cell response
APC
StimulusTH 1
TH 2
T reg
IFN-
IL-4
IL-10
APC - effect on T cell response
TH 1
TH 2
T reg
IFN-
IL-4
IL-10
APC
Stimulus
Cytokines and T cells
• Depending on the antigen, APC may produce different sets of cytokines
• These cytokines determine the type of T cell that proliferates
• Different types of T cells produce specific sets of cytokines
Structure of molecules of IS
• T cell receptor or TCR• MHC class I• MHC class II• Antibody molecules
Knowledge of these structures is helpful in understanding how immune system functions
TCR - alpha, beta chains
alpha chain
beta chain
variable region
variable region
constant region
T cell receptor structure
Alberts et al.
TCR - gamma, delta chains
gamma chain
delta chain
variable region
variable region
constant region
Immunoglobulin super-family
Many molecules in the immune system have an Ig-like structure and hence, belong to the “Ig superfamily”.
Alberts et al.
MHC I and II structure
Albertset al.