Transcript 05 T-Cell
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 • 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 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 Structure of T Cell Receptor Alpha Beta chain chain CHO CHO CHO CHO Variable region “V” Constant region “C” Hinge “H” Disulfide bridge + + + Transmembrane region Cytoplasmic tail 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 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 What Does the T Cell Receptor (TCR) Recognize? 1. 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 Interactions of TH Cell and APC T helper LFA-2 lymphocyte TNF-alpha IL-1 IL-6 IL-12 IL-15 Antigen- LFA-3 presenting cell LFA-1 TCR CD4 peptide ICAM-1 CD28 Class II MHC TNF-beta IFN-gamma GM-CSF IL-4 B7-1/B7-2 (CD80/CD86 Interactions of Tc Cell and Target Cell T cytotoxic lymphocyte LFA-1 TCR CD8 peptide Target cell ICAM-1 LFA-2 Class I MHC LFA-3 T-independent Antigens B cell Figure 17.17 T-Dependent Antigens Figure 17.16 T-dependent and independent antigens • 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 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 Dendritic cells present antigens Figure 17.12 Helper T Cells Figure 17.13 Cell-mediated Cytotoxicity Figure 17.14 Nonspecific Cells • Activated macrophages: Macrophages stimulated by ingesting Ag or by cytokines • Natural killer cells: Lymphocytes that destroy virusinfected cells, tumor Figure 17.15 Self MHC Restriction in the Thymus 4 low 8 low 48 low Productive TCR rearrangement 4+8+ TCR Sub-capsular region Non-productive TCR rearrangement Not recognise self MHC APOPTOSIS Recognise self MHC TCR recognises 4+8+ self antigens TCR TCR does not recognise self antigens Negative selection 4-8- macrophage Cortex Cortico-medullary region 4+8+ TCR Medulla vessel 4+8TCR 4-8+ TCR Self MHC Restriction in the Thymus T-Cell clonal selection Animation 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 Conventional Antigen Superantigen Antigen presenting cell CHO α2 β2 CHO α2 β2 MHC Class II CHO α1 β1 CHO CHO α1 β1 CHO CHO αV βV CHO CHO αV βV CHO CHO αC βC CHO Antigen T cell receptor CHO αC βC CHO T lymphocyte Super antigen