Natural Killer Cell

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NK Cell

Natural Killer Cells(NK Cells) are a kind of cytotoxic lymphocyte in the innate immune system. They are a type of large granular lymphocyte(LGL) that belongs to the expanding family of innate lymphoid cells(ILC). The name “natural killer” suggests they do not require activation to kill cells lacking MHC class I self-markers. This is critical because harmful cells without MHC I markers cannot be detected and destroyed by other immune cells, like T lymphocyte cells.

Based on the signals from several activating and inhibitory receptors, NK cells have a rapid response to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens. They can recognize and kill stressed cells without antibodies and MHC (major histocompatibility complex I), which allows for faster immune reaction than most immune cells.

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NK Cell Types

NK Cells are classified as CD56-bright, CD-56-dim.

CD56- bright NK cells exert the influence by cytokine releasing, this is similar to T helper cells. This kind of NK cells are the majority of NK cells in bone marrow, secondary lymphoid tissue, liver, and skin. They have preferential killing of highly proliferative cells with immuno-regulatory tole.
CD56-dim NK cells have cell killing ability in peripheral blood, CD56-dim NK cells are CD16 positive (CD16 is the key mediator of antibody-dependent cellular cytotoxicity – ADCC).

CD56-bright can transition into CD56-dim by acquiring Cd16. Therefore, NK cells eliminate virus-infected cells by CD16-mediated ADCC.

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Cell Reference

NK Cell Receptors

NK cell receptor are different from the function. Natural cytotoxicity receptors induce cell apoptosis and death after directly indicate infection of cells. MHC-independent receptors apply the alternative pathway to induce apoptosis of infected cells. The activation of natural kill cell is determined by the balance of inhibitory and activating receptor stimulation. NK cell receptor types:

Activating Receptors

  • Ly49
  • NCR
  • CD16
  • TLR
Antimicrobial

Inhibitory Receptors

  • Killer-cell immunoglobulin-like receptors (KIRs)
  • CD94, NKG2
  • ILT, LIR
  • Ly49
Immunomodulatory
Cell Application

Function

  • Cytolytic granule mediated cell apoptosis
  • Antibody-dependent cell-mediated cytotoxicity (ADCC)
  • Cytokine-induced NK and Cytotoxic T lymphocyte (CTL) activation
  • Tumor cell surveillance
  • Clearance of senescent cells

Application

  • Anticancer therapy
  • CAR-NK cells
  • NK-92 cells
  • NKG2D-Fc fusion protein
  • TLR ligands
Disease Treatment
Natural Killer Cells
Cell Application

NK Cell Therapy

NK cell therapy can boost levels of enhanced NK cells in cancer patients, as NK cell function is compromised in cancer. NK cell therapy is allogeneic, donated blood in the laboratories are applied for treatment rather than the patients’ own. This option make NK cell therapy readily available for medical treatment. NK Cell Therapy Advantages:

  • NK cells are faster to prepare, as it only takes 24 hours to ready.
  • It is a treatment option for chemotherapy-resistant acute myeloid leukemia (AML).
  • Cytokine-induced NK and Cytotoxic T lymphocyte (CTL) activation
  • NK cell therapy has few side effects, comparing to other cancer treatments, like: chemotherapy, radiation.