Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of

M Eriksson1, G Leitz, E Fällman

  • 1Umeå Center for Molecular Pathogenesis (UCMP), Umeå University, S-901 87 Umeå, Sweden. mikael.eriksson@ucmp.umu.se

Inhibitory receptors expressed on natural killer (NK) cells abrogate positive signals upon binding corresponding major histocompatibility complex (MHC) class I molecules on various target cells. By directly micromanipulating the effector-target cell encounter using an optical tweezers system which allowed temporal and spatial control, we demonstrate that Ly49-MHC class I interactions prevent characteristic cellular responses in NK cells upon binding to target cells. Furthermore, using this system, we directly demonstrate that an NK cell already bound to a resistant target cell may simultaneously bind and kill a susceptible target cell. Thus, although Ly49-mediated inhibitory signals can prevent many types of effector responses, they do not globally inhibit cellular function, but rather the inhibitory signal is spatially restricted towards resistant targets.

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
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...
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...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...