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Cell-Mediated Immunity CMI

Cell-Mediated Immunity CMI. Specialized lymphocytes, mostly T cells, respond to intracellular Ags After differentiating in the thymus, T cells migrate to lymphoid tissue T cells differentiate into effector T cells when stimulated by an Ag Some effector T cells become memory cells. T Cells.

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Cell-Mediated Immunity CMI

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  1. Cell-Mediated ImmunityCMI • Specialized lymphocytes, mostly T cells, respond to intracellular Ags • After differentiating in the thymus, T cells migrate to lymphoid tissue • T cells differentiate into effector T cells when stimulated by an Ag • Some effector T cells become memory cells

  2. T Cells • Helper T Cells (CD4, TH) • TH1 Activate cells related to cell-mediated immunity • TH2 Activate B cells to produce eosinophils, IgM, and IgE • Cytotoxic T Cells (CD8, TC) • Destroy target cells with perforin

  3. T Cells • Delayed Hypersensitivity T Cells (TD) (CD4) • Associated with allergic reaction, transplant rejection, and tuberculin skin test • Suppressor T cells (TS) (CD8) • Turn off immune response when Ag no longer present

  4. Alphachain Beta chain Variable region “V” CHO CHO CHO CHO Constant region “C” Hinge “H” Disulfide bridge + Transmembrane region + + Cytoplasmic tail Structure of T Cell Receptor

  5. Structure of T Cell Receptor (TCR) • Two polypeptide chains, α and β, of roughly equal length • Both chains consist of a variable (V) and a constant (C) region • α chain V region has a joining (J) segment • β chain V region has both a J and diversity (D) segment

  6. Structure of T Cell Receptor(continued) • Hypervariable regions in V contribute to diversity of TCR • TCR recognizes portions of MHC molecule and peptide bound in the groove

  7. What Does the T Cell Receptor (TCR) Recognize? • Only fragments of proteins (peptides) associated with MHC molecules on surface of cells • Helper T cells (TH) recognize peptide associated with MHC class II molecules • Cytotoxic T cells (Tc) recognize peptide associated with MHC class I molecules

  8. peptide Interactions of TH Cell and APC T helper lymphocyte TCR LFA-2 LFA-1 CD28 TNF-alpha IL-1 IL-6 IL-12 IL-15 TNF-beta IFN-gamma GM-CSF IL-4 CD4 Antigen- presenting cell LFA-3 ICAM-1 B7-1/B7-2 (CD80/CD86 Class II MHC

  9. peptide Interactions of Tc Cell and Target Cell T cytotoxic lymphocyte TCR LFA-1 LFA-2 CD8 Target cell Class I MHC ICAM-1 LFA-3

  10. T-independent Antigens B cell Figure 17.17

  11. T-Dependent Antigens Figure 17.16

  12. T-dependent and independent antigens

  13. Self MHC Restriction • T cells recognize foreign antigen associated with self MHC • No value for individual to have T cells that recognize foreign antigen associated with foreign MHC • Self MHC restriction occurs in thymus

  14. Process of Self MHC Restriction in Thymus • T cells with TCR recognizing self MHC molecules are retained – “positive selection” • Retained T cells with TCR recognizing self peptide associated with self MHC are eliminated – “negative selection” • Self MHC-restricted T cells are released

  15. Dendritic cells present antigens Figure 17.12

  16. Helper T Cells Figure 17.13

  17. Cell-mediated Cytotoxicity Figure 17.14

  18. Nonspecific Cells • Activated macrophages: Macrophages stimulated by ingesting Ag or by cytokines • Natural killer cells: Lymphocytes that destroy virus-infected cells, tumor Figure 17.15

  19. Medulla vessel 4 - 8 + TCR 4 + 8 - TCR Self MHC Restriction in the Thymus 4 low 8 low 4 - 8 low Sub-capsular region Productive TCR rearrangement Non-productive TCR rearrangement APOPTOSIS 4 + 8 + TCR Not recognise self MHC Recognise self MHC macrophage 4 + 8 + TCR TCR recognisesself antigens Cortex TCR does not recognise self antigens Negative selection Cortico-medullary region 4 - 8 - 4 + 8 + TCR

  20. Self MHC Restriction in the Thymus

  21. T-Cell clonal selection Animation

  22. Superantigens • Proteins produced by pathogens • Not processed by antigen presenting cells • Intact protein binds to variable region of β chain on TCR of T cells and to MHC class II on antigen presenting cells (APC) • Large numbers of activated T cells release cytokines having pathological effects

  23. Conventional Antigen Antigen presenting cell α2 β2 α2 β2 CHO CHO MHC Class II α1 β1 α1 β1 CHO CHO CHO CHO Super antigen Antigen αV αV βV βV CHO CHO CHO CHO T cell receptor αC βC αC βC CHO CHO CHO CHO T lymphocyte Superantigen

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