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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 class switching to IgG
  • 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
  •  Macrophages
Interferon-γ
  • 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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