U01.02.009 Natural killer cells

Natural Killer (NK) cells are a unique type of lymphocyte that is an integral part of the innate immune system. They play a crucial role in the early defense against viral infections and tumor formation by recognizing and destroying abnormal cells.

Mechanism of Action

Cytotoxic Activity
NK cells kill their targets by releasing cytotoxic granules containing perforin and granzymes. Perforin forms pores in the target cell membrane, allowing granzymes to enter and induce apoptosis (programmed cell death).
Antibody-Dependent Cellular Cytotoxicity (ADCC)
NK cells also kill cells through a process called ADCC. This occurs when NK cell surface receptor CD16 binds to the Fc region of an IgG antibody attached to a target cell, triggering NK cell activation and cytotoxicity.
Activation and Enhancement
- NK cell activity is enhanced by cytokines such as IL-2, IL-12, IFN-α, and IFN-β.
- NK cells are activated by either the absence of MHC class I molecules on the target cell surface or the presence of stress-induced ligands.

Key Features of NK Cell Function

Function	Description
Perforin and Granzyme Release	NK cells use these proteins to create pores and induce apoptosis in target cells.
Cytokine-Enhanced Activity	IL-2, IL-12, IFN-α, and IFN-β enhance NK cell activity.
MHC Class I Absence Detection	NK cells kill cells lacking MHC class I molecules, often a sign of viral infection or malignancy.
Antibody-Dependent Cytotoxicity	NK cells bind to antibodies coating target cells and induce cell death.

Key Features of NK Cell Function

Points to Remember

NK cells are part of the innate immune system and act without prior sensitization.
Their cytotoxicity is directed against virus-infected cells and tumor cells.
Perforin and granzymes are essential for NK cell-mediated apoptosis.
NK cells are activated by both cytokines and the absence of MHC class I molecules on target cells.
NK cells can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) through CD16 binding.

Bibliography Reference Links

Abbas, A.K., & Lichtman, A.H. (2018). Basic Immunology: Functions and Disorders of the Immune System. Link
Murphy, K., Weaver, C. (2016). Janeway’s Immunobiology. Link

USMLE Step 1 Review Series

Curriculum

U01.02.009 Natural killer cells

Mechanism of Action

Key Features of NK Cell Function

Points to Remember

Bibliography Reference Links

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