Natural killer (NK) cells – Definition, Structure, Function, Mechanism

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What are Natural Killer (NK) Cells? – Definition of NK Cells

  • Large granular lymphocytes are the morphological description of natural killer (NK) cells. These cells are referred to as natural killer cells due to their capacity to eliminate certain virally infected and tumour cells without prior sensitization.
  • Their actions are not improved by exposure and are not virus-specific.
  • 5–10% of peripheral lymphocytes are NK cells, which are located in the spleen and peripheral circulation.
  • NK cells originate in the bone marrow and lack TCR, but have killer activation receptors and killer inhibition receptors.
  • In addition, they possess NK T cells, a subpopulation of T cells that shares some functional properties with NK cells.
  • In contrast to NK cells, these NK T cells are triggered by lipids, glycolipids, and hydrophobic peptides provided by a nonclassical class I molecule CD1D, and they produce significant quantities of cytokines, particularly IL-4.
  • NK cells are primarily responsible for eliminating virus-infected cells and malignancies. They accomplish this via secreting cytotoxins such as perforins and granzymes comparable to those of cytotoxic T cells, as well as by FasL-mediated apoptosis.
  • They eliminate viruses without the presence of particular antibodies through a process known as ADCC. IL-12 and gamma interferons are both powerful NK cell activators.

Properties of natural killer cells

  • Large lymphocytes with granular structures.
  • Lack T-cell receptor, CD3 proteins, surface IgM and IgD, and surface IgM and IgD.
  • Prior exposure has no effect on the level of activity.
  • Thymus is not necessary for growth.
  • In a case of severe combined immunodeficiency, the number remains normal.

NK Cells and T Cells Share Some Features

  • NK cells are lymphoid cells generated from bone marrow that have a common early progenitor with T cells; however, their precise lineage is still being determined. They express membrane markers that are characteristic of monocytes and granulocytes, as well as T-cell-specific markers.
  • NK cells express distinct sets of membrane-bound chemicals. It is unknown whether this variability reflects subpopulations of NK cells or distinct activation or maturation stages of these cells.
  • CD2, the 75-kDa subunit of the IL-2 receptor, is one of the membrane molecules expressed by NK cells. Almost all NK cells also express CD16 (or FcRIII), a receptor for the Fc portion of IgG.
  • Anti-CD16 monoclonal antibody depletion eliminates nearly all NK-cell activity in peripheral blood.
  • Although NK cells share characteristics with T lymphocytes, they do not develop primarily in the thymus. The NK-cell populations of nude mice, which lack a thymus and have few or no T cells, are functioning. Unlike T and B cells, NK cells do not undergo receptor gene rearrangement. This is evidenced by the development of NK cells in mice in which the recombinase genes RAG-1 or RAG-2 have been deleted.
  • In addition, while SCID mice lack T and B cells, functioning populations of NK cells can be readily demonstrated.
  • The capacity of NK cells and other innate immune defence systems to defend animals devoid of adaptive immunity.

Structure of Natural Killer (NK) Cells

  • Natural killer cells are big, granular lymphocytes generated from bone marrow. The cytoplasm of the cell contains azurophilic granules containing hydrolytic and digesting enzymes.
  • NK cells are bigger in diameter than other lymphocytes of a similar kind. These lymphocytes lack the receptors seen on T and B cells.
  • The Wright-Giemsa stain reveals the presence of these cells, which account for around 5% of peripheral circulating lymphocytes.
  • Natural Killer cells exist in a variety of morphologies and display microvilli, particularly in the region of contact between effector and target.
  • These cells have granules with two separate compartments. The outer compartment contains trumetaphosphatase and lysosome-associated phosphatase acid enzymes.
  • The inner compartment is composed of structural components and is devoid of enzyme activity.
  • During degranulation, a specific region of the cytoplasm creates numerous vacuole-like regions made up of granules and granular debris.
  • Additionally, the cytoplasm contains organelles such as mitochondria and polysomes.
  • Against thick granules and pseudopodia, the nucleus is twisted with unique polarity.
  • Different activating and inhibiting receptors that detect distinct membrane proteins are located on the surface of natural killer cells.
Approaches for NK Cell Immunotherapy
Approaches for NK Cell Immunotherapy

Natural killer (NK) cell receptors

  • NK cell receptors can also be distinguished according on their function. Natural cytotoxicity receptors trigger apoptosis (cell death) instantly after attaching to Fas ligands, which signify infection of a cell.
  • The MHC-independent receptors (explained above) trigger apoptosis in infected cells via an alternative mechanism.
  • The activation of natural killer cells is determined by the relative stimulation of inhibitory and activating receptors. If the inhibitory receptor signalling is more predominant, for example, NK cell activity will be repressed; if the activating signal is more apparent, NK cell activity will be activated.
  • NK cell receptor types (including inhibitory and some activating members) are distinguished by their structures, as illustrated by the following examples:

Activating receptors

  • Ly49 (homodimers), receptors belonging to the rather old C-type lectin family, are multigenic in mice, whereas humans have only one pseudogenic Ly49, the receptor for classical (polymorphic) MHC I molecules.
  • Upon stimulation, NCR (natural cytotoxicity receptors), which are type 1 transmembrane proteins of the immunoglobulin superfamily, induce NK death and IFN release. They bind viral ligands such as hemagglutinins and hemagglutinin neuraminidases, as well as certain bacterial ligands and cellular ligands associated with tumour formation, such as PCNA.
  • In particular, CD16 (FcIIIA) plays a role in antibody-dependent cell-mediated cytotoxicity by binding immunoglobulin G.

Inhibitory receptors

  • KIRs are the primary receptors for both classical MHC I (HLA-A, HLA-B, and HLA-C) and nonclassical Mamu-G (HLA-G) in nonhuman primates. Certain KIRs are unique to particular HLA subtypes. Most KIRs are dominant and inhibitory. Regular cells express MHC class 1, so KIR receptors recognise them and block NK cell destruction.
  • CD94/NKG2 (heterodimers), a receptor belonging to the C-type lectin family, is conserved in both rodents and primates and recognises nonclassical (also nonpolymorphic) MHC I molecules, such as HLA-E. Expression of HLA-E at the cell surface is dependent on the presence of a nonamer peptide epitope derived from the signal sequence of classical MHC class I molecules, which is produced sequentially by signal peptide peptidase and the proteasome. This is an indirect method for assessing the amounts of classical (polymorphic) HLA molecules.
  • ILT and LIR (immunoglobulin-like receptor) are newly found Ig receptor family members.
  • There are both activating and inhibiting isoforms of Ly49 homodimers. Although they are physically unrelated to KIRs, they are functional homologues of KIRs in mice, including their expression pattern. Ly49s are receptors for polymorphic (classical) MHC I molecules.

Recognition of Infected and Stressed Cells by NK Cells

Distinguish infected and stressed cells

  • NK cells discriminate infected and stressed cells from healthy cells, and NK cell activation is regulated by a balance of activating and inhibiting receptor signals.
  • Multiple families of these receptors exist. These receptors identify chemicals on the surface of other cells and provide activating or inhibiting signals that stimulate or suppress NK responses, respectively.
  • In general, activating receptors identify ligands on infected and damaged cells, whereas inhibitory receptors identify healthy normal cells.
  • The outcome of an interaction between an NK cell and another cell is controlled by the integration of signals created by the NK cell’s array of inhibitory and activating receptors, which interact with ligands on the other cell.
  • Due to the stochastic nature of their production, the spectrum of activating and inhibiting receptors expressed by various NK cells in a given individual is quite diverse.
  • Consequently, an individual’s NK cells will react to various types of bacteria or infected cells.
  • In addition, the genes encoding the majority of these receptors are polymorphic, meaning that there are multiple variants of the genes in the population, so that each individual expresses a slightly different form of the receptors.

Expression of inhibitory receptors

  • The majority of natural killer (NK) cells carry inhibitory receptors that detect class I major histocompatibility complex (MHC) molecules, which are ordinarily found on the cell surface of virtually all healthy cells in the body.
  • In addition to their involvement in regulating NK cell activation, class I MHC molecules show on the cell surface peptides originating from cytoplasmic proteins, including microbial proteins, for identification by CD8+ T lymphocytes.
  • For the time being, it is essential to realise that NK cells and T cells use fundamentally different types of receptors to recognise class I MHC molecules. In contrast to T cells, the majority of NK receptors for class I MHC suppress NK activation.
  • This is advantageous because normal cells express class I MHC molecules, but many viruses and other causes of cell stress inhibit class I MHC expression on the cell surface.
  • Consequently, NK cells perceive the presence of class I MHC molecules as indicators of a normal, healthy self, whereas their absence indicates infection or harm.
  • Infected or stressed cells will not transmit inhibitory signals to NK cells. NK cells are also likely to receive activating signals via activating receptors from the same infected cells.
  • In the end, the NK cell will be activated to emit cytokines and kill the infected or stressed cell. This capacity of NK cells to become activated by host cells lacking class I MHC is referred to as “recognition of missing self.”
Functions of activating and inhibitory receptors of NK cells
Functions of activating and inhibitory receptors of NK cells – A, NK activating receptors identify ligands on target cells and activate protein tyrosine kinase (PTK), the activity of which is regulated by inhibitory receptors that recognise class I MHC molecules and activate protein tyrosine phosphatases (PTP). NK cells cannot effectively eliminate healthy cells expressing class I MHC. B. If a virus infection or other stress inhibits class I MHC expression on infected cells and induces the expression of additional activating ligands, the NK cell inhibitory receptor is not activated and the activating receptor functions unopposed to trigger NK cell responses, such as killing of target cells and cytokine secretion. C. Cells stressed by infection or neoplastic transformation may express higher levels of activating ligands, which bind NK cell activating receptors and stimulate more tyrosine phosphorylation than can be eliminated by inhibitory receptor related phosphatases, leading in cell death. The structural characteristics and ligands of inhibiting and activating NK cell receptors.

Immunoreceptor tyrosine-based inhibition motif (ITIM)

  • Immunoreceptor tyrosine-based inhibition motif (ITIM) is a structural motif in the cytoplasmic tails of NK cell inhibitory receptors that interacts with substances that impede the signalling pathways of activating receptors.
  • ITIMs contain phosphorylated tyrosine residues upon ligand interaction to the inhibitory receptor. This results in the recruitment and activation of phosphatases, which remove phosphates from a number of signalling proteins or lipids produced by signalling pathways downstream of NK activating receptors.
  • In the end, the signalling functions of activating receptors are inhibited. ITIMs are located in the cytoplasmic tails of receptors other than NK inhibitory receptors.
  • The main group of NK inhibitory receptors is composed of killer cell immunoglobulin-like receptors (KIRs), which are immunoglobulin (Ig) superfamily members.
  • Antibody (also known as Ig) molecules were the first to possess a structural domain called an Ig fold, which is shared by all members of this family. KIRs bind diverse molecules of class I MHC.
  • As noted previously, a second major group of NK inhibitory receptors belongs to the C-type lectin family, which contains proteins with carbohydrate-binding capabilities.
  • One of these receptors is the heterodimer CD94/NKG2A, which detects the HLA-E molecule of class I MHC. Intriguingly, HLA-E shows peptides generated from other class I MHC molecules, so CD94/NKG2A is essentially a surveillance receptor for numerous class I MHC molecules.
  • Leukocyte Ig-like receptors (LIRs), a third family of NK inhibitory receptors, are likewise Ig superfamily members that bind class I MHC molecules, albeit with lesser affinity than the KIRs, and are more abundantly expressed on B cells than NK cells.
Structure and ligands of activating and inhibitory receptors of NK cells
Structure and ligands of activating and inhibitory receptors of NK cells – Examples of inhibitory and activating NK cell receptors and their ligands. CD16 and the natural cytotoxic receptors (NCRs) associate with ζ chain homodimers, FcεRIγ homodimers, or ζ-FcεRIγ heterodimers. There are multiple different KIRs, with varying ligand specificities.

Recognition of a heterogeneous group of ligands

  • Activating receptors on NK cells identify a heterogeneous array of ligands, some of which may be expressed on normal cells and others of which are produced primarily on stressed, infected, or altered cells.
  • For several of these receptors, the molecular characteristics of the ligands are inadequately defined.
  • The enhanced expression of ligands on unhealthy cells that bind to activating receptors on NK cells may result in signals that overwhelm the signals from inhibitory receptors, particularly if class I MHC is also diminished or absent from the unhealthy cell.

Promote target cell killing and cytokine secretion

  • The majority of activating NK receptors share a structural motif in their cytoplasmic tails known as an immunoreceptor tyrosine-based activation motif (ITAM) that engages in signalling processes that boost target cell death and cytokine production.
  • In some of these receptors, the ITAM as well as the extracellular ligand-binding region are included on a single polypeptide chain.
  • In other receptors, such as FcεRIγ, ζ,, and DAP12, the ITAMs are in distinct polypeptide chains that do not bind ligand but are noncovalently connected with the ligand-binding chain.
  • ITAMs are also found in the cytoplasmic tails of other multichain immunological signalling receptors, such as the antigen receptors on T and B cells.
  • After ligand attachment to NK cell activating receptors, cytoplasmic kinases phosphorylate tyrosine residues inside the ITAMs, other protein kinases are attracted to the changed ITAMs and activated, and these kinases contribute to further signalling by phosphorylating other proteins.
  • As previously noted, numerous NK cell activating receptors are members of the C-type lectin or KIR families, which also contain inhibitory receptors. Some of the activating receptors appear to bind class I MHC molecules, similar to the inhibitory receptors, although it is unknown how infected or injured cells selectively activate these receptors.

How NK Cells Kill infected cells and phagocytosed microbes?

  • NK cells have the effector activities of destroying infected cells and activating macrophages to eliminate phagocytosed microorganisms.
  • The NK cell–mediated cytotoxic mechanism is largely identical to that of CD8+ CTLs.
  • Similar to CTLs, NK cells contain granules carrying substances that facilitate the death of target cells. Granule exocytosis releases these proteins near to the target cells when NK cells are activated.
  • Perforin, a granule protein of NK cells, enhances the entry of granzymes, another granule protein, into the cytoplasm of target cells. Granzymes are enzymes that trigger a series of signalling events that result in the apoptotic death of target cells.
  • The signalling pathways responsible for apoptosis. By destroying infected viral and intracellular bacterial cells, NK cells eradicate infection reservoirs.
  • Some cancers, particularly those of hematopoietic origin, are targets for natural killer (NK) cells, possibly because tumour cells do not exhibit typical quantities or types of class I MHC molecules.
  • Similarly to IFN- produced by T cells, IFN- produced by NK cells activates macrophages and enhances their ability to destroy phagocytosed bacteria.
  • IFN- generated by NK cells in lymph nodes can also direct naive T cells to differentiate into TH1 cells.
  • NK cells play various critical roles in defence against intracellular pathogens. They eliminate virally infected cells before antigen-specific CTLs may become completely active, i.e., within the initial few days of viral infection.
  • Early in the course of a viral infection, IL-12 and IL-15 stimulate the expansion and activation of NK cells, which then destroy infected cells, particularly those with diminished amounts of class I MHC molecules.
  • Moreover, NK cell-secreted IFN-γ stimulates macrophages to kill phagocytosed microorganisms. This IFN-γ–dependent NK cell–macrophage response can control an intracellular bacterial infection, such as Listeria monocytogenes, for several days or weeks, allowing T cell–mediated immunity to develop and remove the infection.
  • NK cell depletion increases vulnerability to infection by some viruses and intracellular microorganisms. In the absence of T cell–mediated immunity, the NK cell response of T-cell-deficient mice may be adequate to control infection with such microorganisms for a time, but the animals eventually perish.
  • By eliminating infected cells that have evaded CTL-mediated immune attack by lowering production of class I MHC molecules, NK cells may also play a crucial role later in the body’s response to infection.
  • Because NK cells are capable of killing specific tumour cells in vitro, it has been hypothesised that they also serve to eliminate malignant clones in vivo.
Functions of NK cells.
Functions of NK cells – A, NK cells identify ligands on infected or otherwise stressed cells and eliminate the host cells. NK cells remove infectious reservoirs and defective cells in this manner. B, in response to IL-12 generated by macrophages, NK cells emit IFN-γ, which activates macrophages to destroy phagocytosed microorganisms.

Functions of Natural Killer (NK) Cells

Natural Killer (NK) cells are a vital part of the body’s immune system that play a crucial role in fighting against infections, cancer cells, and other abnormal cells. These cells are a type of lymphocyte and are a part of the innate immune system. In this section, we will discuss the different functions of NK cells and how they work to protect the body from harmful invaders.

  1. Cytolytic activity of NK cells: One of the primary functions of NK cells is to exhibit cytolytic activity against antigens. NK cells are equipped with granules that are present in their cytoplasm. These granules contain perforin and granzymes, which are proteins that help in killing the infected cells. When NK cells come in contact with an infected cell, they release the contents of their granules onto the infected cell, causing the cell to undergo apoptosis or programmed cell death.
  2. Antibody-dependent cell-mediated cytotoxicity (ADCC): NK cells are also involved in ADCC, where antibodies bound to antigens are recognized by specific receptors present on the surface of NK cells. The antibody-coated antigens bind to the NK cells’ receptors, causing the release of granules, leading to the death of the infected cells. This process helps the body to fight against viral infections, especially when the viral load is high.
  3. Activation by cytokines: NK cells can also be activated by cytokines released by stressed cells as a result of viral infection. The activated NK cells, along with activated cytotoxic T cells, activate macrophages for phagocytosis. This process helps to clear the infected cells from the body and promote healing.
  4. Lack of antigen-specific cell surface receptors: NK cells usually lack antigen-specific cell surface receptors, which enables them to react with antigens immediately without any prior exposure. This feature makes them important in the early stages of infections when the body has not yet developed an immune response.
  5. Immunotherapy: NK cells have become a popular target for cancer immunotherapy. They are known to play a crucial role in the immunosurveillance of tumor cells. They can directly induce the death of tumor cells even in the absence of surface adhesion molecules and antigenic molecules. Immunotherapeutic approaches are aimed at enhancing the cytolytic activity of NK cells to target cancer cells effectively.
  6. Innate and Adaptive immune response: Although NK cells are considered part of the innate immune system, recent studies have revealed that NK cells display different adaptive features like the expansion of subsets, increased longevity, and a more potent response on the second exposure. This shows that NK cells not only have innate but also adaptive immune features that help the body in the long term.
  7. Uterine NK cells: Uterine NK cells are a distinct group of NK cells found in the uterus. These cells have lesser cytotoxicity, which is essential for a successful pregnancy. These cells suppress the mother’s immune system as pregnancies involve two parents with tissue that does not match. This feature helps prevent the mother’s immune system from attacking the developing fetus.

In conclusion, NK cells are an important part of the immune system, playing a vital role in fighting infections and cancer cells. Their cytolytic activity, ADCC, and activation by cytokines, lack of antigen-specific cell surface receptors, and ability to work with other immune cells, make them important in the early stages of infections. Furthermore, their ability to display both innate and adaptive immune features makes them a valuable target for immunotherapy. Finally, uterine NK cells play a crucial role in the success of pregnancy by suppressing the mother’s immune system.

Natural killer (NK) cells Summary

  • Immunologists found natural killer cells by accident while assessing the in vitro activity of tumor-specific cells isolated from animals with tumours.
  • Mice that had not been inoculated and mice with unrelated tumours served as negative controls.
  • To the investigators’ consternation, the controls also demonstrated considerable tumour cell lysis. Characterization revealed that a population of big granular lymphocytes was responsible for this nonspecific tumour cell death.
  • The cells, dubbed natural killer (NK) cells due to their nonspecific cytotoxicity, account for 5–10% of the recirculating lymphocyte population.
  • These cells contribute to the immune system’s defence against viruses and malignancies. Due to the fact that NK cells produce a variety of immunologically significant cytokines, they play crucial functions in immune regulation and have a significant impact on both innate and adaptive immunity.
  • Specifically, IFN-γ production by NK cells can influence macrophage participation in innate immunity by stimulating phagocytic and microbicidal activities.
  • IFN-γ generated from NK cells can affect the TH1 vs TH2 commitment of helper T cell populations by inhibiting TH2 expansion and stimulating TH1 development via macrophage and dendritic cell production of IL-12.
  • The Chediak-Higashi syndrome described in the Clinical Focus exemplifies the catastrophic effects of an NK cell deficiency.
  • NK cells participate in the first immune response to some viruses and intracellular bacteria. IFN-, IFN-, and IL-12 each promote NK activity.
  • In the course of a viral infection, the concentration of these cytokines increases rapidly, followed by a wave of NK cells that reaches its peak in around three days.
  • NK cells are the initial line of defence against virus infection, limiting viral replication for approximately 7 days while CTL-P cells undergo activation, proliferation, and differentiation into functional CTLs.
  • A young woman who was completely devoid of NK cells exemplifies the significance of these cells in the fight against viral infections. Despite having normal T- and B-cell counts, this patient suffered from severe varicella virus and life-threatening CMV infections.

Natural killer cells vs Cytotoxic t cells

Natural killer (NK) cells and cytotoxic T cells (CTLs) are two types of immune cells that play important roles in defending the body against infections and cancer. While both NK cells and CTLs are capable of killing infected or abnormal cells, there are some key differences between the two cell types.

  1. Origin and Development: NK cells are a type of lymphocyte that originates from the bone marrow and matures in the peripheral blood and lymphoid tissues. In contrast, CTLs originate from T cells and mature in the thymus.
  2. Cell Surface Receptors: NK cells are characterized by the presence of surface receptors that allow them to recognize and kill infected or abnormal cells without prior exposure. In contrast, CTLs require prior exposure to specific antigens before they can recognize and kill infected or abnormal cells.
  3. Specificity: NK cells have a broad specificity and can recognize and kill a wide variety of target cells, including virus-infected cells and cancer cells. In contrast, CTLs have a narrow specificity and can only recognize and kill cells that present a specific antigen.
  4. Killing Mechanism: NK cells use a variety of mechanisms to kill target cells, including the release of cytotoxic granules and the production of cytokines. In contrast, CTLs use cytotoxic granules that contain molecules like perforin and granzyme to induce cell death in target cells.
  5. Role in Immune Response: NK cells are an important part of the innate immune system and are involved in the early defense against infections and cancer. In contrast, CTLs are part of the adaptive immune system and are involved in the elimination of specific pathogens or abnormal cells.

In summary, while both NK cells and CTLs are capable of killing infected or abnormal cells, they differ in their origin and development, cell surface receptors, specificity, killing mechanisms, and role in the immune response.

What kills cancer cells in the body naturally?

The body has several natural mechanisms to kill cancer cells, including:

  1. Natural Killer (NK) Cells: NK cells are a type of white blood cell that can recognize and directly kill cancer cells. They do this by recognizing specific proteins on the surface of cancer cells that are not present on normal, healthy cells.
  2. Cytotoxic T Cells: Cytotoxic T cells are another type of white blood cell that can kill cancer cells. They do this by recognizing cancer cells that are displaying abnormal proteins on their surface, which are often the result of DNA mutations that occur during the development of cancer.
  3. Apoptosis: Apoptosis is a process of programmed cell death that occurs in normal cells as well as cancer cells. In normal cells, apoptosis helps to eliminate damaged or old cells from the body. In cancer cells, apoptosis can be induced by various treatments like chemotherapy, radiotherapy, and immunotherapy.
  4. Immune System Modulation: The immune system can also be modulated to target cancer cells more effectively. For example, immune checkpoint inhibitors can block certain proteins on cancer cells that inhibit the immune response, allowing the immune system to better recognize and attack the cancer cells.

Overall, the body has several natural mechanisms to kill cancer cells. However, in some cases, these mechanisms may not be sufficient to eliminate all cancer cells, and additional treatments like chemotherapy, radiation therapy, and immunotherapy may be necessary.

FAQ

Where Are Natural Killer Cells Found?

Natural killer cells are sentinels of the immune system that patrol the body in search of contaminated and malignant cells. Consequently, NK cells are ubiquitous and present in the majority of human organs. The largest quantities are found in the bloodstream, the uterus, the lungs, and the liver.

From where NK cells are Originated?

Stem cells in the bone marrow, lymph nodes, spleen, or tonsils differentiate into natural killer cells. 5 to 20% of circulating white blood cells in the human body are mature NK cells.

What are natural killer cells?

Natural killer (NK) cells are a type of lymphocyte, which is a white blood cell that plays a crucial role in the immune system. NK cells are called “natural killers” because they are able to recognize and kill infected or abnormal cells without prior exposure to a specific antigen.
NK cells are part of the innate immune system, which provides the first line of defense against infections and cancer. They are found in the blood, lymphoid tissues, and various organs throughout the body. NK cells are capable of killing a wide range of target cells, including virus-infected cells, tumor cells, and cells that have been damaged or stressed.
NK cells use several mechanisms to recognize and kill target cells. They have surface receptors that can detect changes in the expression of molecules on the surface of infected or abnormal cells, allowing them to distinguish between healthy and unhealthy cells. Once activated, NK cells can release cytotoxic granules that contain molecules like perforin and granzyme, which induce cell death in the target cell. NK cells can also produce cytokines that help to activate other cells of the immune system.
NK cells play an important role in immunosurveillance, which is the process by which the immune system identifies and eliminates abnormal cells before they develop into cancer. In addition, NK cells are involved in the response to viral infections and in the regulation of immune responses during pregnancy.
Overall, natural killer cells are a critical component of the immune system that helps to defend the body against infections and cancer by recognizing and killing infected or abnormal cells.

Are natural killer cells innate or adaptive?

Natural killer (NK) cells are generally considered a part of the innate immune system, which is the first line of defense against infections and cancer. Unlike adaptive immune cells such as T cells and B cells, which require specific recognition of antigens and clonal expansion to become activated, NK cells can respond to a wide variety of pathogens and abnormal cells without prior exposure.
However, recent studies have suggested that NK cells may also possess some adaptive features. For example, some studies have shown that NK cells can undergo clonal expansion in response to certain viral infections or cytokine stimulation, similar to what is seen with adaptive immune cells. In addition, certain subsets of NK cells have been found to display memory-like properties, which allows for a more rapid and potent response to subsequent infections.
Overall, while natural killer cells are typically considered to be innate immune cells, their ability to display some adaptive features suggests a more complex role in the immune system.

Are natural killer cells lymphocytes?

Yes, natural killer (NK) cells are a type of lymphocyte, which is a white blood cell that plays a crucial role in the immune system. Lymphocytes are divided into two main types: B cells and T cells, which are part of the adaptive immune system, and NK cells, which are part of the innate immune system.
NK cells share many characteristics with other lymphocytes, including the ability to recognize and respond to foreign antigens. However, unlike B cells and T cells, NK cells do not possess antigen-specific receptors and are able to recognize and kill target cells without prior exposure to a specific antigen.
Overall, natural killer cells are a specialized type of lymphocyte that play an important role in the innate immune response to infections and cancer.

What do natural killer cells do?

Natural killer (NK) cells are a type of white blood cell that play an important role in the immune system. They are part of the body’s innate immune response and serve as the first line of defense against infections and cancer.
NK cells are primarily known for their ability to identify and kill abnormal cells in the body, including virus-infected cells, cancer cells, and cells that have been damaged or stressed. They do this by recognizing specific proteins on the surface of these cells, which are often absent or reduced in normal healthy cells.
In addition to their cytotoxic activity, NK cells also secrete cytokines and chemokines, which help to activate and recruit other immune cells to the site of infection or inflammation. They also play a role in regulating the immune response by interacting with other immune cells and modulating their activity.
NK cells are particularly important for immunosurveillance, which is the process by which the immune system constantly monitors the body for abnormal or foreign cells. They are able to identify and eliminate these cells before they can cause harm or spread throughout the body.
Overall, natural killer cells play a crucial role in the immune system by identifying and eliminating abnormal or infected cells and helping to regulate the immune response.

are natural killer cells phagocytes?

No, natural killer (NK) cells are not phagocytes. Phagocytes are a type of immune cell that are able to engulf and destroy foreign particles, such as bacteria and debris, by a process called phagocytosis.
In contrast, NK cells do not engulf or digest foreign particles. Instead, they are able to directly recognize and kill abnormal cells, such as virus-infected or cancerous cells, through a process called cytotoxicity. NK cells accomplish this by releasing specialized granules that contain molecules like perforin and granzymes, which can cause the target cell to undergo apoptosis (programmed cell death).
While NK cells are not phagocytes, they do work in conjunction with other immune cells, such as macrophages, which are phagocytes. NK cells can activate macrophages to phagocytose and clear debris or dead cells from the body. This cooperation between different types of immune cells is an important aspect of the immune system’s ability to fight off infections and maintain tissue homeostasis.

How do natural killer cells recognize their targets?

Natural killer (NK) cells recognize their targets through a complex system of activating and inhibitory receptors on their surface. These receptors allow NK cells to distinguish between healthy, normal cells and abnormal or infected cells, including cancer cells.
NK cells have both activating and inhibitory receptors on their surface. Activating receptors recognize specific molecules on the surface of target cells, which trigger a signaling cascade that leads to the activation of the NK cell and the release of cytotoxic granules. Inhibitory receptors, on the other hand, recognize “self” molecules on healthy cells, which prevent the NK cell from attacking these cells.
The balance between activating and inhibitory signals is critical for NK cell function. If the activating signals are stronger than the inhibitory signals, the NK cell will become activated and attack the target cell. If the inhibitory signals are stronger, the NK cell will not attack the healthy cell.
One important activating receptor on NK cells is called NKG2D. This receptor recognizes stress-induced molecules that are often upregulated on the surface of tumor cells, infected cells, and other abnormal cells. When NKG2D binds to its ligands on the target cell, it triggers the activation of the NK cell and the release of cytotoxic granules.
NK cells also have other activating receptors, including NKp46, NKp44, and NKp30, which can recognize a wide variety of ligands on target cells, including viral proteins, bacterial molecules, and stress-induced molecules.
Overall, NK cells use a sophisticated system of activating and inhibitory receptors to recognize and attack abnormal or infected cells, while sparing healthy cells.

How do natural killer cells kill?

Natural killer (NK) cells are capable of killing target cells through a process called cytolysis or apoptosis. NK cells have several mechanisms for inducing cell death in their target cells.
One of the primary ways that NK cells kill their target cells is by releasing cytotoxic granules, which contain proteins called perforin and granzymes. Perforin creates pores in the membrane of the target cell, while granzymes enter the cell and trigger a cascade of events that lead to cell death. This process is known as the perforin/granzyme pathway.
NK cells can also induce target cell death through the activation of death receptors on the surface of the target cell. One such receptor is called Fas, and when it is bound by its ligand, it triggers a signaling cascade that leads to apoptosis or programmed cell death.
In addition, NK cells can induce target cell death by secreting cytokines, which are signaling molecules that can activate various cellular pathways leading to apoptosis.
Overall, NK cells have multiple mechanisms for killing their target cells, which allows them to respond to a wide variety of infectious or abnormal cells in the body. By selectively targeting cells that are infected or transformed, NK cells play a crucial role in immune surveillance and protecting the body against cancer and viral infections.

References

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  • Hu W, Wang G, Huang D, Sui M, Xu Y. Cancer Immunotherapy Based on Natural Killer Cells: Current Progress and New Opportunities. Front Immunol. 2019 May 31;10:1205. doi: 10.3389/fimmu.2019.01205. PMID: 31214177; PMCID: PMC6554437.
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