Lecture 9: T-cell Mediated Immunity

Questions to Consider

How do T cells know where to go?

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?

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

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 pre- programmed to recognize.

After exposure to the antigen they proliferate, leave the lymph node and migrate to infected tissues where they function as effector cells.

Naive T cells Express Adhesion Molecules That Target Their Migration to Lymph Nodes/Peyer’s Patches

Lymph NodeGut-associated Lymphoid Tissue

GALT

Divergent Expression of Adhesion Molecules Differentially Target Migration of Naïve and Effector T Cells

Antigen-exposedT cell

Mucosally-targetedNaïve T cell

All T cells

Naïve and Effector T Cells Express Different Levels of Membrane Proteins

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

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.

There is Functional Variation Among Different Antigen Presenting Cells

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

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

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

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

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

CCR7 is Induced and Directs DC Migration to the Lymph Node

PAMP= Pathogen-associated molecular patterns

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

Adhesion Molecule Interaction Stabilizes the Binding of T Cells to APCs

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

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

T cell Tolerance Results From Antigen Recognition Without Costimulatory Signal

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

Adhesion Molecule Interaction Involved in CD8 CTL Immune Surveillance

Once Activated, CTLs Can Become Serial Killers

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

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

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

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

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

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

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?