1 IMMUNOLOGY NF2252, Introduction of Immunology and Immune System
Immunology molecular medicine 3 Conleth Feighery.
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Transcript of Immunology molecular medicine 3 Conleth Feighery.
![Page 1: Immunology molecular medicine 3 Conleth Feighery.](https://reader036.fdocuments.net/reader036/viewer/2022062314/56649f1c5503460f94c32770/html5/thumbnails/1.jpg)
Immunology molecular medicine 3
Conleth Feighery
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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
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CYTOKINES
Cells of the immune system ‘talk’ to each other by producing cytokines - like ‘text messages’ informing cells
what their function should be!
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CD4+ T cells - MHC II interaction
APCT h
cytokines
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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
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Cytokine products of cells
APCT h
IL-1IL-2
CD28 B7
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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
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Cytokine products of cells
APCT h
IL-1
IL-2 Receptors - cytokines bind to specific cell receptors
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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
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IL-1 helps T cell activation
APCT h
IL-1 producedby APC
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T cell co-stimulation
Essential to T cell activation, division and replication
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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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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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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
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IL-2 required for T cell growth
APCT h
IL-2
CD28 B7
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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
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T cell cytokines affect B cells
T h B
IL-4,5,6
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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
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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
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Lymph node - histology
Lymphoid follicles
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Interferon gamma helps kill intracellular infections
MOT h
TBInterferon - gamma
IFN-
IFN- activates macrophage killingmechanisms
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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
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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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T cytotoxic cell - cytolytic mechanism
APCT cytxTarget cell
virusLytic granules
perforinEnzymes, water, salts
Granules - contentperforin,enzymes
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Pattern recognition receptors
Various stimulibind to receptorson APC and influence APC reaction
APC
TOLL Stimulus
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Pattern recognition receptors
Various stimulibind to receptorson APC and influence APC reaction
Different cytokinesAPC
B7
Toll-like receptors
Stimulus
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APC –effect on T cell response
APC
StimulusTH 1
TH 2
T reg
IFN-
IL-4
IL-10
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APC - effect on T cell response
TH 1
TH 2
T reg
IFN-
IL-4
IL-10
APC
Stimulus
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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
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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
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TCR - alpha, beta chains
alpha chain
beta chain
variable region
variable region
constant region
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T cell receptor structure
Alberts et al.
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TCR - gamma, delta chains
gamma chain
delta chain
variable region
variable region
constant region
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Immunoglobulin super-family
Many molecules in the immune system have an Ig-like structure and hence, belong to the “Ig superfamily”.
Alberts et al.
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MHC I and II structure
Albertset al.