1. Chapter 11 T-cell Activation and Differentiation Dr. Capers
Immunology

2. Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 10
T-Cell Maturation, Activation,
and Differentiation
Copyright © 2007 by W. H. Freeman and Company

3. 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

4. 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

5. 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

6. 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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9. Superantigens Exogeneous Endogeneous 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

11. 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)

13. Treg Cells Shown to inhibit proliferation of other T cells in vitro
CD4+CD25+
Shown to inhibit development of autoimmune diseases

14. 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