Natural Killer Cell

Aka: Natural Killer Cell, NK cell, Large Granular Lymphocyte

1. See Also
   1. Major Histocompatibility Complex 1 (MHC-1)
   2. White Blood Cell (Leukocyte)
   3. Lymphocyte
   4. Immune System
   5. B-Lymphocyte (B Cell)
   6. T-Lymphocyte (T-Cell)
2. Physiology
   1. Background
      1. Lymphocytes providing protection against Intracellular Bacteria and viruses, as well as cancer cells
         1. Respond to intracellular Viral Infections within first 3 days
         2. Similar destruction of virally infected cells as with Cytotoxic T Cells
      2. Part of Innate Immunity in which response is not based on prior exposure to pathogen
         1. Contrast with antibodies, B-Cells and T-Cells which have a learned pathogen response (Adaptive Immunity)
         2. Lack the Specificity of Adaptive Immunity
         3. Do not require MHC markers on Target Cells (unlike other Lymphocytes)
            1. In contrast, NK cells appear to Target Cells without MHC proteins
      3. Natural Killer Cell Markers
         1. CD56 positive
         2. CD3 negative
         3. Lack other markers found on B Cells and T Cells
   2. Activation of Natural Killer Cells
      1. Macrophage and Dendritic Cell derived Cytokines (e.g. Interleukin 12, type 1 Interferons)
   3. Deactivation of Natural Killer Cells
      1. Natural Killer Cells bind Major Histocompatibility Complex 1 (MHC-1)
      2. MHC-1 is present on normal cells and it inactivates NK cells
      3. MHC-1 is NOT expressed by infected cells
         1. NK activating receptor Ligand is expressed
         2. NK cells bind infected cells and destroy them
   4. NK cell mechanisms of infected cell destruction
      1. Cytoplasmic granules released, resulting in Target Cell lysis
         1. Perforin
            1. Generates pores on cells targeted for destruction
         2. Granzyme
            1. Induces programmed cell death (apoptosis) on entry into Target Cells
      2. Cytokines
         1. Tumor Necrosis Factor A (TNFa)
         2. Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
         3. Chemokines (CCL1-5 and CCL-8)
         4. Interferon-Gamma (IFN-g)
            1. Activates Macrophages for Phagocytosis
   5. Image: NKC Mediated Destruction of Infected Host Cells
      1. 
3. References
   1. Guyton and Hall (2006) Medical Physiology, p. 419-50
   2. Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL