Download Lecture 9: T-cell Mediated Immunity

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 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.
Naive T cells Express Adhesion Molecules That Target
Their Migration to Lymph Nodes/Peyer’s Patches
Gut-associated Lymphoid Tissue
Lymph Node
GALT
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
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?