Kuby Immunology 6/e
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Transcript Kuby Immunology 6/e
Chapter 11
T-cell Activation and Differentiation
Initiating event of adaptive immune
response
○ Interaction between niave T cell and an
antigen-presenting cell
○ Signal 1 – provided by antigen-specific TCR
engagement
○ Signal 2 – provided by contact with
costimulatory ligand expressed by APC
- Example - CD28
○ Signal 3 - cytokines
T cell Activation
Initiated by TCR-CD3 complex with
processed antigen on MHC molecule
○ CD8+ cells with Class I
○ CD4+ cells with Class II
Initiates cascade of biochemical events
○ Inducing resting T cell to enter cell cycle,
proliferate, differentiate into memory and
effector T cells
T cell Activation
Cascade of biochemical events leading
to gene expression:
Interaction of signal and molecule (example:
TCR + MHC and antigen)
Generation of “second messenger” that
diffuses to other areas of cell
Protein kinases and protein phosphatases
are activated or inhibitied
Signals are amplified by enzyme cascades
Click on link to see example
https://www.youtube.com/watch?v=tMMrTRnFdI4
T cell Activation
Gene products after activation
○ Immediate genes (1/2 hour of recognition)
Transcription factors (c-Myc, NFAT, NF-κB)
○ Early genes (1-2 hours from recognition)
IL-2, IL2R, IL-6, IFN-γ
○ Late genes (more than 2 days later)
Encode adhesion molecules
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Superantigens
Bind to BOTH the TCR and
MHC
Can cause over-activation
Overproduction of TH-cell
cytokines, leading to
systemic toxicity
Exogeneous
Variety of exotoxins
secreted by some Gram+
bacteria
Endogeneous
Cell membrane proteins
encoded by viruses
T-Cell Differentiation
CD4+ and CD8+ cells leave thymus and enter circulation in
G0 phase
○ Naïve cells (condensed chromatin, little cytoplasm)
○ About twice as many CD4+
Naïve cell recognized MHC-antigen complex
○ Initiated primary response
○ After 48 hours, enlarges into blast cell and undergoes
repeated rounds of cell division
○ Differentiate into:
- Effector cells – cytokine secretion, B-cell help
- Memory cells – long lived, respond with heightened
activity (secondary response)
Treg Cells
Shown to inhibit proliferation of other T
cells in vitro
CD4+CD25+
Shown to inhibit development of
autoimmune diseases
Cell Death and T Cell Populations
Apoptosis plays critical role
Deletion of potentially autoreactive
thymocytes
Deletion of T cell populations after activation
○ Fas and FasL pathway to induce self death