Transcript Kuby Immunology 6/e - Dr. Jennifer Capers, PhD

Chapter 11
T-cell Activation and Differentiation
Dr. Capers
Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 10
T-Cell Maturation, Activation,
and Differentiation
Copyright © 2007 by W. H. Freeman and Company

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
http://www.youtube.com/watch?v=tMMrTRnFdI4&f
eature=player_detailpage
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