Killer cell immunoglobulin-like receptors (KIRs)

Definition

Killer cell immunoglobulin-like receptors (KIRs) are a family of receptors expressed on natural killer (NK) cells and some T cells, playing a critical role in regulating immune responses. They are primarily involved in distinguishing between healthy and infected or transformed cells, thereby influencing the cytotoxic activity of NK cells. KIRs interact with specific molecules on target cells, providing a balance between activating and inhibitory signals that determine whether an NK cell will attack a target.

5 Must Know Facts For Your Next Test

1. KIRs can be categorized into two main groups: those that deliver inhibitory signals and those that provide activating signals to NK cells.
2. The interaction between KIRs and their ligands, often MHC class I molecules, is crucial for maintaining self-tolerance and preventing autoimmunity.
3. Different individuals have varied KIR genotypes, which can influence susceptibility to infections, cancer development, and response to therapies.
4. KIRs are encoded by a cluster of genes on chromosome 19 and show significant diversity in the population.
5. The balance between activating and inhibitory signals from KIRs is essential for the effective functioning of NK cells during immune surveillance.

Review Questions

• How do KIRs influence the activity of natural killer (NK) cells in recognizing target cells?
  • KIRs influence NK cell activity by providing a balance of activating and inhibitory signals when they interact with their ligands on target cells. When KIRs bind to MHC class I molecules on healthy cells, they typically send inhibitory signals to NK cells, preventing them from attacking. However, if a target cell lacks MHC class I expression or presents stress-induced ligands, activating KIRs may signal NK cells to initiate cytotoxic action. This regulatory mechanism is crucial for distinguishing between healthy and abnormal cells.
• Discuss the significance of the diversity of KIR genotypes among individuals and its implications for immune responses.
  • The diversity of KIR genotypes among individuals significantly impacts immune responses, including susceptibility to diseases such as infections and cancer. Different KIR haplotypes can influence how effectively NK cells respond to various pathogens or tumors. For example, certain KIR alleles are associated with better control of viral infections or improved outcomes in cancer immunotherapy. Understanding these differences can help tailor personalized treatments based on an individual's KIR genotype, enhancing the effectiveness of therapeutic strategies.
• Evaluate how KIR interactions with MHC molecules contribute to the overall balance of the immune response in health and disease.
  • KIR interactions with MHC molecules play a pivotal role in maintaining the balance of the immune response by regulating NK cell activity. In healthy states, this interaction helps prevent unnecessary destruction of normal tissues by ensuring that NK cells recognize self-cells as safe. However, in disease conditions like infections or cancers, altered expression of MHC molecules can disrupt this balance, allowing NK cells to become activated and eliminate damaged or infected cells. This dual function highlights the importance of KIR-MHC interactions in both protecting the body from pathogens while also safeguarding against autoimmunity.

Related terms

Natural Killer (NK) Cells: A type of lymphocyte that plays a crucial role in the innate immune system by identifying and killing virus-infected cells and tumors.

Major Histocompatibility Complex (MHC): A set of molecules displayed on cell surfaces that help the immune system recognize foreign molecules, which KIRs often interact with.

Cytotoxic T Lymphocytes (CTLs): A subtype of T cells that kill cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways.