Role of natural killer cells in immunotoxicity: an update

Jacques Descotes1, Guillaume Ravel

  • 1Poison Center and Pharmacovigilance Unit, 162 Avenue Lacassagne, 69424 Lyon Cedex 03, France. jacques-georges.descotes@chu-lyon.fr

Insights

Measuring natural killer cell activity is debated for predicting chemical-induced immunotoxicity due to inconsistent results. New methods are needed to identify reliable markers for assessing immune system risks.

Area of Science:

  • Immunology
  • Toxicology
  • Innate Immunity

Background:

  • Natural killer (NK) cells are crucial for innate immunity against viral infections and cancer.
  • NK cell activity measurement is a standard nonclinical test for immunotoxicity evaluation.
  • Chemicals like agrochemicals and environmental agents can impair NK cell function, but human health impacts are unclear.

Purpose of the Study:

  • To evaluate the utility of measuring natural killer cell activity in predicting chemical-induced immunotoxicity.
  • To address the ambiguous situation regarding the value of NK cell activity assays in safety assessments.
  • To highlight limitations in current NK cell activity analyses and suggest future directions.

Main Methods:

  • Review of existing literature on NK cell activity and chemical exposure.
  • Analysis of data regarding the correlation between NK cell function and clinical outcomes.
  • Discussion of current guidelines for nonclinical safety assessment of pharmaceuticals.

Main Results:

  • A lack of direct evidence links chemical-induced NK cell activity impairment to significant human health issues like infections or cancers.
  • Few pharmaceuticals, even potent immunosuppressants, consistently depress NK cell activity.
  • The predictive value of NK cell activity measurement for immunotoxicity remains debatable.

Conclusions:

  • Current methods for measuring natural killer cell activity may have limitations, contributing to debatable predictive value.
  • Further research using advanced techniques to identify relevant NK cell activation markers is warranted.
  • Investigating the underlying mechanisms of NK cell modulation by chemicals is essential for improved immunotoxicity assessment.

Related Concept Videos

Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...