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Updated: Jan 3 2022

Cell-Mediated Immunity

  • Overview
    • Cell-mediated immunity is the result of cooperation between innate and adaptive immunity to
      • destroy virus infected cells before they can produce more virus
      • damage pathogenic bacteria, fungi, and parasites
      • eliminiate cancerous cells that lack normal cell surface proteins
    • Cells involved in immunity can be divided into
      • primary effector cells such as
        • granulocytes
        • macrophages
        • CD8+ T-cells
        • natural killer (NK) cells
      • secondary support cells such as
        • CD4+ helper T-cells
        • dendritic cells
    • Cell-mediated immunity can result from
      • innate immune response
      • activation of T-cells
      • coordination of cells via cytokines
  • Important Cytokines in Cellular Immunity
    • Cytokines are key coordinators of the cellular immune response by promoting
      • vascular changes near the site of inflammation
      • recruiting of other target cells
      • differentiation of target cells
      • signaling to distant organs
    • Cytokines can be secreted by a variety of cells including
      • activated macrophages
      • helper T-cells
      • killer T-cells
      • Important Cytokines in Cellular Immunity
      • Cytokine
      • Function
      • Secreted by
      • Interleukin-1
      • Causes fever and acute inflammation
      • Activates endothelial expression of adhesion molecules
      • Macrophages
      • Interleukin-2
      • Stimulates growth and survival of T-cells and NK cells
      • All T-cells
      • Interleukin-3
      • Stimulates the growth and differentiation of bone marrow cells
      • All T-cells
      • Interleukin-4
      • Induces differentiation of helper T-cells into Th2 subtype cells
      • Promotes growth of B-cells and enhances class switching to IgG and IgE
      • Th2 cells
      • Interleukin-5
      • Promotes growth and differentiation of B cells and eosinophils
      • Promotes class switching to IgA
      • Th2 cells
      • Interleukin-6
      • Stimulates fever
      • Causes increased production of acute phase proteins by liver
      • Macrophages
      • Interleukin-8
      • Stimulates chemotaxis by neutrophils to sites of infection
      • Macrophages
      • Interleukin-10
      • Decreases inflammatory response by inhibiting macrophages and dendritic cells
      • Decreases expression of MHC molecules and Th1 cytokines
      • Regulatory T-cells
      • Interleukin-12
      • Promotes differentiation of T-cells into Th1 cells
      • Activates killing by NK cells
      • Macrophages
      • Tumor necrosis factor-α
      • Alters vascular endothelium to promote leakage
      • Recruits diverse white blood cells to site of release
      • Induce fever
      • Macrophages
      • Interferon-α/β
      • Activates antiviral defense system of cells
      • Down regulates protein synthesis
      • Upregulates MHC expression for easy recognition of infected cells
      • All cells
      • Activates macrophages to kill ingested organisms
      • Promotes granuloma formation
      • Increases MHC and antigen presentation by all cells
      • Increases killing by NK cells
      • Th1 cells
  • Effector Mechanisms
    • Macrophage and neutrophil killing depends upon
      • oxygen-dependent mechanisms such as respiratory burst
      • oxygen-independent mechanisms including
        • hydrolytic enzymes that destroy peptides
        • defensins that form holes in bacterial membranes
        • lactoferrin that binds iron and denies it to bacteria
        • lysozyme that cleaves bacterial peptidoglycan walls
    • NK and cytotoxic CD8+ T-cell killing depends upon three mechanisms including
      • exocytosis of cytotoxic granules containing
        • granzymes that are apoptosis activating serine proteases
        • perforin that makes a hole in membranes
      • Fas ligand that directly signals target cells to undergo apoptosis
      • cytokine signaling mainly through TNF pathways that also induce apoptosis
    • Notably NK cells are inhibited by MHC complexes on the surface of cells
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