Transcript Immunol-molec-med-3-2ndmed

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
APC
Th
cytokines
CD4+ T cells interact with APC and other cells by
releasing cytokines. APC also release cytokines.
APC
Th
cytokines
The type of cytokines that are released are crucial to the
type of immune response which results
Cytokine products of cells
APC
Th
CD28 B7
IL-1
IL-2
Cytokine product of cells
APC
Th
CD28 B7
IL-1
IL-2
Cells interact through the production
and release of cytokines - these bind
to cells and affect their function
Cytokine products of cells
APC
Th
IL-1
IL-2
Receptors - cytokines bind to
specific cell receptors
Cytokines
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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
Th
APC
IL-1 produced
by APC
T cell co-stimulation
Essential to T cell activation, division
and replication
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
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
Stimulated T cell - IL-2 produced
CD4
APC
Th
IL-2 receptor
CD28
B7
IL-2
IL-2 binds to receptor on cell - causes cell growth, division
IL-2 required for T cell growth
APC
Th
CD28 B7
IL-2
CTLA-4 - negative signal
CD4
APC
Th
CTLA-4 B7
T cell receptor binding to antigen = signal 1
CTLA-4 binds to B7 - inhibits stimulation
T cell cytokines affect B cells
B
Th
IL-4,5,6
T cell cytokines affect B cells
B
Th
IL-4, 5 and 6 all
involved in B cell
stimulation and Ig
production
IL-4, IL-5, IL-6
Lymph node - cartoon
Alberts et al.
T cell activation takes place in lymph node tissue
T cell help for B cells takes place in lymph. follicles
Lymph node - histology
Lymphoid
follicles
Interferon gamma helps kill
intracellular infections
MO
Th
IFN-g activates
macrophage killing
mechanisms
TB
Interferon - gamma
IFN-g
T cytotoxic cell - recognition of
antigen, role of CD8
CD8
virus
APC
T cytx
Target cell
MHC I
T cytotoxic cell reacting with virus antigen
presented by MHC class I molecule
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
T cytotoxic cell - cytolytic
mechanism
Lytic granules
Granules - content
perforin,
enzymes
virus
APC
T cytx
Target cell
Enzymes, water, salts
perforin
Pattern recognition receptors
TOLL
Stimulus
APC
Various stimuli
bind to receptors
on APC and influence
APC reaction
Pattern recognition receptors
Toll-like
receptors
Stimulus
B7
APC
Various stimuli
bind to receptors
on APC and influence
APC reaction
Different cytokines
APC –effect on T cell response
Stimulus
APC
TH 1
IFN-g
TH 2
IL-4
T reg
IL-10
APC - effect on T cell response
Stimulus
APC
TH 1
IFN-g
TH 2
IL-4
T reg
IL-10
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
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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
constant region
variable region
alpha chain
beta chain
variable region
T cell receptor structure
Alberts et al.
TCR - gamma, delta chains
constant region
variable region
gamma chain
delta chain
variable region
Immunoglobulin super-family
Alberts et al.
Many molecules in the immune system have an Ig-like
structure and hence, belong to the “Ig superfamily”.
MHC I and II structure
Alberts
et al.