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Principles of Immunology T Cell-Mediated Immunity 3/28/06

Principles of Immunology T Cell-Mediated Immunity 3/28/06. “Each of us needs to be the change we wish to see in the world” Ghandi. Word/Terms List. ADCC Effector cells GVH reaction Perforin. T Cell-mediated Immunity.

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Principles of Immunology T Cell-Mediated Immunity 3/28/06

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  1. Principles of ImmunologyT Cell-Mediated Immunity3/28/06 “Each of us needs to be the change we wish to see in the world” Ghandi

  2. Word/Terms List • ADCC • Effector cells • GVH reaction • Perforin

  3. T Cell-mediated Immunity Principal function-Response to intracellular pathogens and cells expressing foreign antigens Recirculation-Naïve T cells circulate between the blood stream and the lymphatic system Antigen presentation-Naïve T cell cells only respond to APCs

  4. Priming of T Cells • Three types of effector T cells • CD8 (TC) • CD4 (TH1) • CD4 (TH2) • Each type • Responds to different types of Ags • Activated by different Ag presentation • Has different effector function

  5. T Cell Effector Types • CD8 • Viruses and intracellular bacteria • MHC I • Cytotoxic effector cells • CD4 TH1 • Bacteria and parasites in APCs • MHC II • Effectors activate macrophages, CTLs and induce B cells to produce opsonins • CD4 TH2 • Extracellular bacteria and toxin producers • MHC II • Activate B cells to produce multiple antibody classes

  6. T Cell Adhesion • T cells pass through endothelial cells (extravasation) • Endothelial cells and T cells both have cell adhesion molecules (CAMs) • Various CAMs

  7. Cell Adhesion Molecules • Selectins • Mucins • Integrins • Immunoglobulin superfamily

  8. APCs • Dendritic cells • Macrophages • B cells

  9. Dendritic Cells • Antigen presentation is sole function • Antigenic uptake is followed by migration to lymph nodes • Expression of MHC I, MHC II and B7 • Loses phagocytic property • Secretes chemokines

  10. Macrophages • Involved in both innate and adaptive immunity • May destroy pathogens or present Ag to T cells • Expression of MHC I, MHC II and B7 • Scavenges dead cells

  11. B Cells • Binds soluble antigens • Constitutively expresses MHC II • Induced to express B7

  12. NK Cells • ~5% of lymphocytes • Nonspecific cytotoxicity • No TCR/CD3 • Not MHC restricted • No memory

  13. CTL Cytotoxicity • Conjugate formation • Membrane attack • Dissociation • Target cell death

  14. Conjugate Formation • Cell adhesion • Recognition of MHC I:Ag on target cell

  15. Membrane Attack • Granules in CTLs • Perforin • Granzymes • Exocytosis of granule contents • Perforin action similar to C9 • Granzymes act as nucleases • Fas ligand to Fas triggers target cell death

  16. Dissociation and Target Cell Death • CTL interacts for about five minutes • Dissociates and can conjugate with other target cells • Target dies after several hours

  17. Antibody-Dependent Cell-Mediated Cytotoxicity • NK cells, macrophages, neutrophils • Bind to Fc region of Ab • Multiple cytotoxic mechanisms

  18. Graft vs. Host Reaction • Immunocompromised recipient • Lymphocytes of donor attack allogeneic antigens of recipient • Splenomegaly

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