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Updated: Jan 3 2019

T-Cell Activation


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  • Introduction
    • The activation of T-cells must be tightly controlled to allow for
      • selective proliferation of pathogen specific T-cells
      • anergy of self-reactive T-cells
      • prevention of autoimmune disorders
    • Four events are required for proper T-cell activation including
      • antigen processing and presentation by antigen presenting cells that
        • display antigens as peptides bound to MHC
        • migrate to draining lymph nodes
      • specific binding of the T-cell receptor to the antigen concurrently with
        • binding of CD4 coreceptors to MHC class II in helper T-cells
        • binding of CD8 coreceptors to MHC class I in killer T-cells
      • costimulation of the T-cell by antigen presenting cells through interaction between
        • B7 (CD80/CD86) on dendritic cells
        • CD28 on T-cells
      • differentiation through cytokine signaling pathways at the time of activation
    • After T-cell activation, activated cells migrate to the periphery where
      • killer T-cells identify infected cells and release toxic substances
      • helper T-cells undergo further differentiation into subtypes
  • Three Signal Hypothesis
    • Antigen presenting cells interact with naive T-cells in secondary lymphoid organs where
      • they allow T-cells to recognize their ingested antigens
      • they provide costimulatory input
    • T-cells require all signals to be present in order to activate
    • T-cells will undergo apoptosis or become anergic (state of inactivity) if
      • they receive only one of the activation signals so that
        • autoreactive cells can be removed
        • benign materials are not mistakenly recognized as harmful
      • they receive signals that the infection is cured and inflammation has subsided
      • Three Signal Hypothesis
      • Feature
      • Signal 1
      • Signal 2
      • Signal 3
      • Function
      • Leverage specificity of T-cell receptors to detect antigen
      • Ensure binding to antigen presenting cell with antigen of interest
      • Distinguish between erroneous binding of T-cell receptors and real pathogenic recognition
      • Ensure that the recognized antigen is on an activated antigen presenting cell
      • Convey information about the surrounding environment of the activation site
      • Ensure proper differentiation of the activated T-cells
      • Interacting proteins
      • Antigen bound to MHC type I or II proteins
      • T-cell receptor
      • CD4 or CD8
      • B7 (CD80 and CD86) that are only expressed on activated antigen presenting cells
      • CD28
      • IL-2 (T-cell survival signal)
      • Diverse cytokines
      • Cytokine receptors
      • Associations
      • Super antigens can artificially induce binding of T-cell receptor with MHC
      • Induced anergy or apoptosis if not present in conjuction with signal 1
  • Helper T-Cell Differentiation
    • After activation, helper T-cells further differentiate in response to
      • cytokine signals released by the innate immune system
      • the inflammatory environment of the activation site
      • cross talk with other adaptive cells such as regulatory T-cells
    • Each helper T-cell subtype differs in several ways including
      • general function of the class
      • signals (usually cytokines) required for differentiation
      • secreted factors produced
      • Helper T Cell Subtypes
      • Feature
      • Th1
      • Th2
      • Th17
      • Function
      • Promote cell based immunity
      • Activate macrophages and cytotoxic T-cells
      • Promotes humoral immunity
      • Recruits eosinophils as part of parasite defence
      • Activate neutrophils
      • Differentiation
      • IFN-γ
      • IL-12
      • IL-2
      • IL-4
      • IL-6
      • TGF-β
      • Associations
      • Granuloma formation
      • Tuberculous leprosy
      • Lepromatous leprosy
      • IgE production by B cells
      • Chronic inflammatory conditions
      • Secreted Factors
      • IFN-γ
      • IL-2
      • IL-4
      • IL-5
      • IL-13
      • IL-17
      • IL-21
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