Activation of T Lymphocytes

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Chapter 9

• Activation of T Lymphocytes

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• Activation and effector phases of T cell-mediated
  adaptive immune responses are triggered by
  antigen recognition by T lymphocytes
• Naive T lymphocytes home to secondary lymphoid
  organs, where they may encounter antigens
  presented by mature dendritic cells on class I or
  class II MHC molecules and thus become activated
• Antigen-stimulated T cells that have received
  both "signal one" through the antigen receptor
  and "second signals" via co-stimulatory receptors
  may be induced to secrete cytokines and to
  express cytokine receptors (like IL-2)
• T cell responses decline after the antigen is
  eliminated by effector cells

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Activation of Naive and Effector T Cells by
Antigen
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Phases of T Cell Responses
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SIGNALS FOR T LYMPHOCYTE ACTIVATION
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• The proliferation of T lymphocytes and their
  differentiation into effector and memory cells
  require antigen recognition, costimulation, and
  cytokines

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Recognition of Antigen

• Antigen is always the necessary first signal for
  the activation of lymphocytes, ensuring that the
  resultant immune response is specific for the
  antigen
• Activation of naive T cells requires recognition
  of antigen presented by dendritic cells

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Role of Costimulation in T Cell Activation
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Mechanisms of T cell costimulation by CD28
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The major members of the B7 and CD28 families
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Role of CD40 in T cell activation
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The mechanism of therapeutic costimulatory
blockade
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FUNCTIONAL RESPONSES OF T LYMPHOCYTES
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Changes in surface molecules after T cell
activation
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Cytokines in Adaptive Immune Responses
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Regulation of IL-2 receptor expression
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Biologic actions of IL-2
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Development of Memory T Cells
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Clonal expansion of T cells
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Development of memory T cells
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DECLINE OF T CELL RESPONSES
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• Elimination of antigen leads to contraction of
  the T cell response, and this decline is
  responsible for maintaining homeostasis in the
  immune system
• Costimulation and growth factors like IL-2
  stimulate expression of the anti-apoptotic
  proteins Bcl-2 and Bcl-XL in the activated
  lymphocytes, and these proteins keep cells viable
• The inhibitory receptors CTLA-4 and PD-1,
  apoptosis induced by death receptors of the TNF
  receptor superfamily (such as TNFRI and Fas), and
  regulatory T cells

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