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Specialized lymphocytes, mostly T cells, respond to intracellular Ags After differentiating in the thymus, T cells migrate to lymphoid tissue T cells differentiate.

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Presentation on theme: "Specialized lymphocytes, mostly T cells, respond to intracellular Ags After differentiating in the thymus, T cells migrate to lymphoid tissue T cells differentiate."— Presentation transcript:

1 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 Cell-Mediated Immunity CMI

2 Helper T Cells (CD4, T H ) –T H 1 Activate cells related to cell-mediated immunity –T H 2 Activate B cells to produce eosinophils, IgM, and IgE Cytotoxic T Cells (CD8, T C ) –Destroy target cells with perforin T Cells

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

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

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? 1.Only fragments of proteins (peptides) associated with MHC molecules on surface of cells Helper T cells (T H ) recognize peptide associated with MHC class II molecules Cytotoxic T cells (Tc) recognize peptide associated with MHC class I molecules

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

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

10 T-independent Antigens Figure B cell

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

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18 Dendritic cells present antigens Figure 17.12

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22 Helper T Cells Figure 17.13

23 Cell-mediated Cytotoxicity Figure 17.14

24 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

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

26 Self MHC Restriction in the Thymus / TCR low TCR low TCR low TCR low Express MHC I Express MHC II No MHC engagement apoptosis 8+ TCR high 8+ TCR high 4+ TCR high 4+ TCR high

27 Self MHC Restriction in the Thymus No interaction with self antigen Interaction with MHC I and self antigen. Interaction with dendritic cells, macrophages and medullary epithelium Interaction with MHC II and self antigen. Interaction with dendritic cells, macrophages and medullary epithelium No interaction with self antigen 8+ TCR high 4+ TCR high TCR induced apoptosis Mature T cell pool

28 Self MHC Restriction in the Thymus

29 T-Cell clonal selection Animation

30 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

31 Conventional Antigen αCβC CHO βVαV α2β2 β1α1 CHO αCβC CHO βVαV α2β2 β1α1 CHO MHC Class II T cell receptor Antigen Super antigen T lymphocyte Antigen presenting cell Superantigen


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