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Immunology

Chapter 11 T-cell Activation and Differentiation Dr. Capers. Immunology. Initiating event of adaptive immune response Interaction between niave T cell and an antigen-presenting cell Signal 1 – provided by antigen-specific TCR engagement

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Immunology

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

  2. 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

  3. 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

  4. 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

  5. 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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  7. 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 • Watch this video: https://www.youtube.com/watch?v=ByZ-DK5DNdM

  8. 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)

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

  10. 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

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