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NK Cells, Markers & Function

What are NK Cells?

Natural Killer (NK) cells were first described in the mid-1970’s as a population of innate lymphocytes that were able to mediate cytotoxicity against tumour cells without prior exposure to a target (Herberman et al., 1975, I and II). NK cells are found in primary and secondary immune compartments, some mucosal tissues and are continually circulating through the vasculature to perform host immunosurveillance. They make up between 5-15% of human peripheral blood cells and 2-3% of splenocytes in mice (Mah and Cooper, 2016). Along with their role in tumour cell surveillance, they are also valued for their early defence against microbial infection.

NK cells vs T Cells

NK cells and T cells are two types of white blood cells that play a role in the immune response. NK cells are responsible for killing infected or damaged cells, while T cells help to regulate the immune response and produce antibodies. Both cell types are important for protecting the body from disease.

The main difference between NK cells and T cells is their function. NK cells are cytotoxic, meaning they can kill infected or damaged cells. T cells are not cytotoxic, but they help to regulate the immune response by producing antibodies.

NK cells are important for protecting the body against viruses and cancer. T cells are important for protecting the body against bacteria and other pathogens.

NK Cells cytotoxic function

Natural killer (NK) cell activity and in particular its cytotoxic function can be modulated by certain cytokines such as interferon-gamma (IFN-gamma), Natural Killer Cells produce three kinds of Natural killer cell granules which are specific, it contains perforin and Natural Killer Cell Granule Protease 3-like 1 (NKGPL1) Natural killer cell granule protease 1 (NKGPC1). Natural Killer Cells express a number of inhibitory receptors that usually have immunoreceptor tyrosine based inhibition motifs in their cytoplasmic regions. Natural Killers also express the ability to modulate NK cells via IL-10.

A lymphocyte is a kind of white blood cell with an abundant nucleus and little cytoplasm which Natural Killer Cells make up about 10% or Natural Killers account for approximately 5-15% of circulating lymphocytes Natural killer cells are cytotoxic lymphocytes Natural Killers attack other tumor cells Natural Killers carry out their anti-tumor activity by releasing Natural Killer Cell granules, Natural Killer Cells have the ability to recognize abnormal cancerous cells without prior immunization, Natural Killers have no antigen specific receptors but Natural Killer Cells can recognise their targets through HLA class I molecules which are highly polymorphic and diverse, Natural Killer Cells lack T cell receptors so Natural Killers cannot be infected by intracellular viruses that infect other white blood cells or Natural Killer Cells kill tumour cells or virus-infected host cells.

NK Cells & T Cell Lymphoma

NK cells are a type of lymphocyte that play a key role in the body's immune response. T cell lymphoma is a cancer that begins in the lymphocytes, which are a type of white blood cell. NK cells help to fight infection and disease by attacking cells that are infected or abnormal. In patients with T cell lymphoma, the NK cells are not able to properly kill the cancer cells. This can lead to the cancer cells spreading and causing more damage. There is currently no cure for T cell lymphoma, but treatment options are available to help manage the disease and extend a patient's life.

NK Cells & T Cell Lymphoma

Natural killer (NK) cells not only provide defense against cancer and infections; they can also modulate the immune response against tumours. Natural Killer Cells are cytotoxic lymphocytes which mediate their anti-tumour activity by releasing cytotoxins in the form of granules, Natural Killer Cells release enzymes like perforin (Pfn) that form pores on the surface of Natural Killer cells is used to fuse Natural Killer cells with tumour cells and Natural Killers release Natural killer cell protease granzyme B (GzmB) which typically is present in small amounts in Natural killer cells but Natural Killers require cytosolic factors to be released so Natural Killers can induce apoptosis within its target cell.

NK Cell Markers

NK cells are a type of white blood cell that play an important role in the body's immune response. They are equipped with various receptors that allow them to recognize and respond to foreign invaders, such as viruses and bacteria.

One of the most important NK cell markers is CD56. This protein is found on the surface of NK cells and is involved in their interactions with other cells. CD56 allows NK cells to bind to and kill cancer cells, as well as infected or damaged tissue.

Other important NK cell markers include CD16 and CD57. CD16 is a receptor that helps NK cells to respond to foreign invaders. It also allows them to bind to and kill cancer cells. CD57 is a protein that is found on the surface of NK cells and is involved in their development and function.

List of Human & Mouse NK Cell Markers

CD4+ & CD8+ markers

Natural Killer Cells are large granular lymphocytes that can be either CD4+ or CD8+. Natural Killer Cells produce at least 18 different immunoregulatory molecules which include transcription factors, cytokines and chemokines as well as the cytotoxic granules containing perforin and granzymes.

Natural Killer Cells are important in the immune system because Natural Killers have the ability to recognize abnormal cells without prior immunization which Natural Killer Cells have no antigen specific receptors, Natural Killers lack MHC class I molecules so Natural Killer Cells cannot be infected by intracellular viruses but can promote viral infection of other cells through cytokine release, Natural Killer Cells recognise their targets via surface proteins encoded by HLA genes which are highly polymorphic and diverse, Natural Killer Cells have a low specificity for different target cells which is why Natural Killers are able to kill both tumour cells and virus-infected or otherwise abnormal healthy host cells.

The use of MHC class I

Natural Killer Cells use class I major histompatibility complex (MHC) peptides to recognize pathological cells. Natural Killer Cells are important because Natural Killer Cells lack T cell receptors, Natural Killers require HLA class I molecules on the surface of other cells to recognize them.

Natural Killers also use MHC class 1 antigens to identify abnormal cancerous cells but Natural Killers do not need prior immunization to detect possible pathogenic cells, Natural Killers do not have antigen specific receptors and Natural Killer Cells cannot be infected by intracellular viruses that infect other white blood cells or Natural Killer Cells kill tumour cells or virus-infected host cells.

NK Cell development

NK cells, similarly to T and B cells, are derived from the common lymphoid progenitor (CLP) and like B cells they are thought to develop in the bone marrow (Geiger and Sun, 2016), although it has also been proposed that NK cells may develop in both the thymus and the liver (Sojka et al., 2014).

However, unlike T and B cells, NK cell receptors are germline-encoded and do not require gene recombination by recombination-activating gene (RAG) recombinase (Lanier et al., 1986). Following the development of NK cells, they undergo terminal maturation in secondary lymphoid tissues, including the lymph nodes and spleen (Geiger and Sun, 2016).

Mature peripheral NK cells can be identified by the upregulation of the cell surface marker CD11b and the downregulation of CD27, with the most immature NK cells being CD27-CD11b-, and the most mature NK cells being CD27-CD11b+. (Chiossone et al., 2009). Furthermore, in parallel with T and B cells, NK cells require common-gamma-chain-dependent cytokine signalling, particularly Interleukin-15 (IL-15), for development, survival, function and to maintain homeostasis (Cooper et al., 2002). Following disruption of IL-15 signalling, NK cell survival is reduced and the NK cells that are present become arrested in an immature state (Vosshenrich et al., 2005).

13th Apr 2022 Sean Mac Fhearraigh PhD

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