Lecture 9: T-cell Mediated Immunity

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1 Lecture 9: T-cell Mediated Immunity

2 Questions to Consider How do T cells know where to go?

3

4 Questions to Consider How do T cells know where to go? How does antigen get targeted to a T cell expressing the appropriate TCR? How is T cell response to self-antigens prevented?

5 The T Cell Response Involves Activation, Proliferation and Differentiation Into Effector Cells

6 Anatomical Localization of Lymphocytes is Determined by Exposure to Antigen Primary lymphoid tissues generate naïve lymphocytes that enter the circulation. These cells must home to an environment wherein they wait for exposure to the antigen that they are preprogrammed to recognize. After exposure to the antigen they proliferate, leave the lymph node and migrate to infected tissues where they function as effector cells.

7 Naive T cells Express Adhesion Molecules That Target Their Migration to Lymph Nodes/Peyer s Patches Lymph Node Gut-associated Lymphoid Tissue GALT

8 Divergent Expression of Adhesion Molecules Differentially Target Migration of Naïve and Effector T Cells All T cells Mucosally-targeted Naïve T cell Antigen-exposed T cell

9 Naïve and Effector T Cells Express Different Levels of Membrane Proteins

10 L-Selectin-expressing Naive T Cells Home To CD34-expressing HEV in Lymph Nodes

11 Antigen Presentation Occurs in Tissues Wherein Naive Lymphocytes Interact With APC Naïve T and B lymphocytes localize to lymph nodes or mucosal Peyer s patches. Antigenic activation of these cells requires interaction with APC. A mechanism is required whereby antigen derived from pathogens infecting peripheral tissues is brought into the lymph nodes for presentation and activation of the appropriate naïve lymphocyte.

12 There is Functional Variation Among Different Antigen Presenting Cells

13 There is Divergent Anatomical Localization of Different Antigen Presenting Cells in Lymph Nodes

14 T Cell Activation Requires A Specific Antigenic Signal and a Generic Co-stimulatory Signal

15 T Cell-expressed CD28 Binding to APC-expressed B7 Provides a Co-Stimulatory Signal

16 T Cell-expressed CTLA-4 Binding to APC-expressed B7 Provides a Inhibitory Signal

17 Langerhans Cells Transport Antigen Into the Lymph Node and Differentiate Into Dendritic Cells

18 PAMP= Pathogen-associated molecular patterns CCR7 is Induced and Directs DC Migration to the Lymph Node

19 Conventional DCs Express B7 and Activate T cells Plasmacytoid DCs Express TLR-7/9 and Produce IFN

20 Adhesion Molecule Interaction Stabilizes the Binding of T Cells to APCs

21 Antigen Recognition Increases T Cell Binding to APCs by Increasing Adhesion Molecule Interaction

22 High Level Expression of B7 by Dendritic Cells Permits Them to Activate Naïve T Cells

23 T cell Tolerance Results From Antigen Recognition Without Costimulatory Signal

24 Transduction of Co-stimulatory Signal Determines Whether T Cell Will Activated or Anergized

25 Adhesion Molecule Interaction Involved in CD8 CTL Immune Surveillance

26 Once Activated, CTLs Can Become Serial Killers

27 Requirement For Co-stimulatory Signal Prevents Induction of CD4 T Cell Response to Self

28 B Cells Focus T Cell Help To Stimulate Production of Its Antibody and to Switch to IgG

29 The T Cell Response Involves Activation, Proliferation and Differentiation Into Effector Cells

30 IL-2 Binds to the Interleukin 2 Receptor and is the Major T Cell Growth Factor

31 Differential Expression of Multichain IL-2 Receptor Permits Variable IL-2 Receptor Affinity

32 Activated CD4 Helper Cells Produce a Broad Range of Cytokines With Diverse Functions

33 Questions to Consider How do T cells know where to go? How does antigen get targeted to a T cell expressing the appropriate TCR? How is T cell response to self-antigens prevented?

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