Neutrophil

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Neutrophil
Blausen 0676 Neutrophil (crop).png
3D rendering of a neutrophil
Neutrophils.jpg
Neutrophils with segmented nuclei surrounded by erythrocytes and platelets. Intra-cellular granules are visible in the cytoplasm (Giemsa stained).
Details
System Immune system
Function Phagocytosis
Identifiers
MeSH D009504
TH H2.00.04.1.02012
FMA 62860
Anatomical terms of microanatomy

Neutrophils (also known as neutrocytes, heterophils or polymorphonuclear leukocytes) are a type of white blood cell. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. [1] They form an essential part of the innate immune system, with their functions varying in different animals. [2]

Contents

They are formed from stem cells in the bone marrow and differentiated into subpopulations of neutrophil-killers and neutrophil-cagers. They are short-lived (between 5 and 135 hours, see § Life span) and highly mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils. [3] [4] [5]

The name neutrophil derives from staining characteristics on hematoxylin and eosin (H&E) histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain a nucleus divided into 2–5 lobes. [6]

Neutrophils are a type of phagocyte and are normally found in the bloodstream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection, environmental exposure, [7] and some cancers, [8] [9] neutrophils are one of the first responders of inflammatory cells to migrate toward the site of inflammation. They migrate through the blood vessels and then through interstitial space, following chemical signals such as interleukin-8 (IL-8), C5a, fMLP, leukotriene B4, and hydrogen peroxide (H2O2) [10] in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance. [11]

Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation; [12] however, due to some pathogens being indigestible, they might not be able to resolve certain infections without the assistance of other types of immune cells.

Structure

Neutrophil granulocyte migrates from the blood vessel to the matrix, secreting proteolytic enzymes to dissolve intercellular connections (to the improvement of its mobility) and envelop bacteria through phagocytosis. NeutrophilerAktion.svg
Neutrophil granulocyte migrates from the blood vessel to the matrix, secreting proteolytic enzymes to dissolve intercellular connections (to the improvement of its mobility) and envelop bacteria through phagocytosis.
Hypersegmented neutrophil Hypersegmented neutrophil - by Gabriel Caponetti,MD.jpg
Hypersegmented neutrophil

When adhered to a surface, neutrophil granulocytes have an average diameter of 12–15 micrometers (µm) in peripheral blood smears. In suspension, human neutrophils have an average diameter of 8.85 µm. [13]

With the eosinophil and the basophil, they form the class of polymorphonuclear cells, named for the nucleus' multilobulated shape (as compared to lymphocytes and monocytes, the other types of white cells). The nucleus has a characteristic lobed appearance, the separate lobes connected by chromatin. The nucleolus disappears as the neutrophil matures, which is something that happens in only a few other types of nucleated cells. [14] : 168  Up to 17% of female human neutrophil nuclei have a drumstick-shaped appendage which contains the inactivated X chromosome. [15] In the cytoplasm, the Golgi apparatus is small, mitochondria and ribosomes are sparse, and the rough endoplasmic reticulum is absent. [14] : 170  The cytoplasm also contains about 200 granules, of which a third are azurophilic. [14] : 170 

Neutrophils will show increasing segmentation (many segments of the nucleus) as they mature. A normal neutrophil should have 3–5 segments. Hypersegmentation is not normal but occurs in some disorders, most notably vitamin B12 deficiency. This is noted in a manual review of the blood smear and is positive when most or all of the neutrophils have 5 or more segments.

Reference ranges for blood tests of white blood cells, comparing neutrophil amount (shown in pink) with that of other cells Reference ranges for blood tests - white blood cells.png
Reference ranges for blood tests of white blood cells, comparing neutrophil amount (shown in pink) with that of other cells

Neutrophils are the most abundant white blood cells in humans (approximately 1011 are produced daily); they account for approximately 50–70% of all white blood cells (leukocytes). The stated normal range for human blood counts varies between laboratories, but a neutrophil count of 2.5–7.5 × 109/L is a standard normal range. People of African and Middle Eastern descent may have lower counts, which are still normal. [16] A report may divide neutrophils into segmented neutrophils and bands.

When circulating in the bloodstream and inactivated, neutrophils are spherical. Once activated, they change shape and become more amorphous or amoeba-like and can extend pseudopods as they hunt for antigens. [17]

In 1973, Sanchez et al. found that the capacity of neutrophils to engulf bacteria is reduced when simple sugars like glucose, fructose as well as sucrose, honey and orange juice were ingested, while the ingestion of starches had no effect. Fasting, on the other hand, strengthened the neutrophils' phagocytic capacity to engulf bacteria. It was concluded that the function, and not the number, of phagocytes in engulfing bacteria was altered by the ingestion of sugars. [18] In 2007 researchers at the Whitehead Institute of Biomedical Research found that given a selection of sugars on microbial surfaces, the neutrophils reacted to some types of sugars preferentially. The neutrophils preferentially engulfed and killed beta-1,6-glucan targets compared to beta-1,3-glucan targets. [19] [20]

Development

Life span

HSC=hematopoietic stem cell, Progenitor=progenitor cell, L-blast=lymphoblast, lymphocyte, Mo-blast=monoblast, monocyte, myeloblast, Pro-M=promyelocyte, myelocyte, Meta-M=metamyelocyte, neutrophil, eosinophil, basophil, Pro-E=proerythroblast, Baso-E=basophilic erythroblast, poly-e=polychromatic erythroblast, ortho-E=orthochromatic erythroblast, erythrocyte, promegakaryocyte, megakaryocyte, platelet Hematopoiesis simple.svg
HSC=hematopoietic stem cell, Progenitor=progenitor cell, L-blast=lymphoblast, lymphocyte, Mo-blast=monoblast, monocyte, myeloblast, Pro-M=promyelocyte, myelocyte, Meta-M=metamyelocyte, neutrophil, eosinophil, basophil, Pro-E=proerythroblast, Baso-E=basophilic erythroblast, poly-e=polychromatic erythroblast, ortho-E=orthochromatic erythroblast, erythrocyte, promegakaryocyte, megakaryocyte, platelet

The average lifespan of inactivated human neutrophils in the circulation has been reported by different approaches to be between 5 and 135 hours. [21] [22]

Upon activation, they marginate (position themselves adjacent to the blood vessel endothelium) and undergo selectin-dependent capture followed by integrin-dependent adhesion in most cases, after which they migrate into tissues, where they survive for 1–2 days. [23] Neutrophils have also been demonstrated to be released into the blood from a splenic reserve following myocardial infarction. [24]

Neutrophils are much more numerous than the longer-lived monocyte/macrophage phagocytes. A pathogen (disease-causing microorganism or virus) is likely to first encounter a neutrophil. Some experts hypothesize that the short lifetime of neutrophils is an evolutionary adaptation. The short lifetime of neutrophils minimizes propagation of those pathogens that parasitize phagocytes (e.g. Leishmania [25] ) because the more time such parasites spend outside a host cell, the more likely they will be destroyed by some component of the body's defenses. Also, because neutrophil antimicrobial products can also damage host tissues, their short life limits damage to the host during inflammation. [23]

Neutrophils will be removed after phagocytosis of pathogens by macrophages. PECAM-1 and phosphatidylserine on the cell surface are involved in this process.

Function

Chemotaxis

Neutrophils undergo a process called chemotaxis via amoeboid movement, which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gradients of molecules such as interleukin-8 (IL-8), interferon gamma (IFN-γ), C3a, C5a, and leukotriene B4, which these cells use to direct the path of their migration.

Neutrophils have a variety of specific receptors, including ones for complement, cytokines like interleukins and IFN-γ, chemokines, lectins, and other proteins. They also express receptors to detect and adhere to endothelium and Fc receptors for opsonin. [26]

In leukocytes responding to a chemoattractant, the cellular polarity is regulated by activities of small Rho guanosine triphosphatases (Rho GTPases) and the phosphoinositide 3-kinases (PI3Ks). In neutrophils, lipid products of PI3Ks regulate activation of Rac1, hematopoietic Rac2, and RhoG GTPases of the Rho family and are required for cell motility. Rac-GTPases regulate cytoskeletal dynamics and facilitate neutrophils adhesion, migration, and spreading. [27] They accumulate asymmetrically to the plasma membrane at the leading edge of polarized cells. Spatially regulating Rho GTPases and organizing the leading edge of the cell, PI3Ks and their lipid products could play pivotal roles in establishing leukocyte polarity, as compass molecules that tell the cell where to crawl.

It has been shown in mice that in certain conditions neutrophils have a specific type of migration behaviour referred to as neutrophil swarming during which they migrate in a highly coordinated manner and accumulate and cluster to sites of inflammation. [28]

Anti-microbial function

Being highly motile, neutrophils quickly congregate at a focus of infection, attracted by cytokines expressed by activated endothelium, mast cells, and macrophages. Neutrophils express [29] and release cytokines, which in turn amplify inflammatory reactions by several other cell types.

In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defense against invading pathogens. Neutrophils have three methods for directly attacking micro-organisms: phagocytosis (ingestion), degranulation (release of soluble anti-microbials), and generation of neutrophil extracellular traps (NETs). [30]

Phagocytosis

Scanning electron micrograph of a neutrophil (yellow) phagocytosing anthrax bacilli (orange). Scale bar is 5 mm. Neutrophil with anthrax copy.jpg
Scanning electron micrograph of a neutrophil (yellow) phagocytosing anthrax bacilli (orange). Scale bar is 5 μm.

Neutrophils are phagocytes, capable of ingesting microorganisms or particles. For targets to be recognized, they must be coated in opsonins  –a process known as antibody opsonization. [17] They can internalize and kill many microbes, each phagocytic event resulting in the formation of a phagosome into which reactive oxygen species and hydrolytic enzymes are secreted. The consumption of oxygen during the generation of reactive oxygen species has been termed the "respiratory burst", although unrelated to respiration or energy production.

The respiratory burst involves the activation of the enzyme NADPH oxidase, which produces large quantities of superoxide, a reactive oxygen species. Superoxide decays spontaneously or is broken down via enzymes known as superoxide dismutases (Cu/ZnSOD and MnSOD), to hydrogen peroxide, which is then converted to hypochlorous acid (HClO), by the green heme enzyme myeloperoxidase. It is thought that the bactericidal properties of HClO are enough to kill bacteria phagocytosed by the neutrophil, but this may instead be a step necessary for the activation of proteases. [31]

Though neutrophils can kill many microbes, the interaction of neutrophils with microbes and molecules produced by microbes often alters neutrophil turnover. The ability of microbes to alter the fate of neutrophils is highly varied, can be microbe-specific, and ranges from prolonging the neutrophil lifespan to causing rapid neutrophil lysis after phagocytosis. Chlamydia pneumoniae and Neisseria gonorrhoeae have been reported to delay neutrophil apoptosis. [32] [33] [34] Thus, some bacteria –and those that are predominantly intracellular pathogens –can extend the neutrophil lifespan by disrupting the normal process of spontaneous apoptosis and/or PICD (phagocytosis-induced cell death). On the other end of the spectrum, some pathogens such as Streptococcus pyogenes are capable of altering neutrophil fate after phagocytosis by promoting rapid cell lysis and/or accelerating apoptosis to the point of secondary necrosis. [35] [36]

Degranulation

Neutrophils also release an assortment of proteins in three types of granules by a process called degranulation. The contents of these granules have antimicrobial properties, and help combat infection. Glitter cells are polymorphonuclear leukocyte neutrophils with granules. [37]

Granule typeProtein
Azurophilic granules (or "primary granules") Myeloperoxidase, bactericidal/permeability-increasing protein (BPI), defensins, and the serine proteases neutrophil elastase, Proteinase 3 and cathepsin G
Specific granules (or "secondary granules") Alkaline phosphatase, lysozyme, NADPH oxidase, collagenase, lactoferrin, histaminase, [38] and cathelicidin
Tertiary granules Cathepsin, gelatinase, and collagenase

Neutrophil extracellular traps

In 2004, Brinkmann and colleagues described a striking observation that activation of neutrophils causes the release of web-like structures of DNA; this represents a third mechanism for killing bacteria. [39] These neutrophil extracellular traps (NETs) comprise a web of fibers composed of chromatin and serine proteases [40] that trap and kill extracellular microbes. It is suggested that NETs provide a high local concentration of antimicrobial components and bind, disarm, and kill microbes independent of phagocytic uptake. In addition to their possible antimicrobial properties, NETs may serve as a physical barrier that prevents further spread of pathogens. Trapping of bacteria may be a particularly important role for NETs in sepsis, where NETs are formed within blood vessels. [41] Finally, NET formation has been demonstrated to augment macrophage bactericidal activity during infection. [42] [43] Recently, NETs have been shown to play a role in inflammatory diseases, as NETs could be detected in preeclampsia, a pregnancy-related inflammatory disorder in which neutrophils are known to be activated. [44] Neutrophil NET formation may also impact cardiovascular disease, as NETs may influence thrombus formation in coronary arteries. [45] [46] NETs are now known to exhibit pro-thrombotic effects both in vitro [47] and in vivo. [48] [49] More recently, in 2020 NETs were implicated in the formation of blood clots in cases of severe COVID-19. [50]

Tumor Associated Neutrophils

TANs can exhibit an elevated extracellular acidification rate when there is an increase in glycolysis levels. [51] When there is a metabolic shift in TANS this can lead to tumor progression in certain areas of the body, such as the lungs. In 2021, Ancey et al. identified how TANs support the growth and progression of tumors unlike normal neutrophils which would inhibit tumor progression through the phagocytosis of tumor cells. Utilizing a mouse model, they identified that both Glut1 and glucose metabolism increased in TANs found within a mouse who possessed lung adenocarcinoma. [51]

Clinical significance

Micrograph showing several neutrophils during an acute inflammation Neutrophils -1.jpg
Micrograph showing several neutrophils during an acute inflammation

Low neutrophil counts are termed neutropenia . This can be congenital (developed at or before birth) or it can develop later, as in the case of aplastic anemia or some kinds of leukemia. It can also be a side-effect of medication, most prominently chemotherapy. Neutropenia makes an individual highly susceptible to infections. It can also be the result of colonization by intracellular neutrophilic parasites.

In alpha 1-antitrypsin deficiency, the important neutrophil elastase is not adequately inhibited by alpha 1-antitrypsin, leading to excessive tissue damage in the presence of inflammation – the most prominent one being emphysema. Negative effects of elastase have also been shown in cases when the neutrophils are excessively activated (in otherwise healthy individuals) and release the enzyme in extracellular space. Unregulated activity of neutrophil elastase can lead to disruption of pulmonary barrier showing symptoms corresponding with acute lung injury. [52] The enzyme also influences activity of macrophages by cleaving their toll-like receptors (TLRs) and downregulating cytokine expression by inhibiting nuclear translocation of NF-κB. [53]

In Familial Mediterranean fever (FMF), a mutation in the pyrin (or marenostrin ) gene, which is expressed mainly in neutrophil granulocytes, leads to a constitutively active acute-phase response and causes attacks of fever, arthralgia, peritonitis, and – eventually – amyloidosis. [54]

Hyperglycemia can lead to neutrophil dysfunction. Dysfunction in the neutrophil biochemical pathway myeloperoxidase as well as reduced degranulation are associated with hyperglycemia. [55]

The Absolute neutrophil count (ANC) is also used in diagnosis and prognosis. ANC is the gold standard for determining severity of neutropenia, and thus neutropenic fever. Any ANC < 1500 cells / mm3 is considered neutropenia, but <500 cells / mm3 is considered severe. [56] There is also new research tying ANC to myocardial infarction as an aid in early diagnosis. [57] [58] Neutrophils promote ventricular tachycardia in acute myocardial infarction. [59]

In autopsy, the presence of neutrophils in the heart or brain is one of the first signs of infarction, and is useful in the timing and diagnosis of myocardial infarction and stroke.

Pathogen evasion and resistance

Just like phagocytes, pathogens may evade or infect neutrophils. [62] Some bacterial pathogens evolved various mechanisms such as virulence molecules to avoid being killed by neutrophils. These molecules collectively may alter or disrupt neutrophil recruitment, apoptosis or bactericidal activity. [62]

Neutrophils can also serve as host cell for various parasites that infects them avoding phagocytosis, including:

Neutrophil antigens

There are five (HNA 1–5) sets of neutrophil antigens recognized. The three HNA-1 antigens (a-c) are located on the low affinity Fc-γ receptor IIIb (FCGR3B :CD16b) The single known HNA-2a antigen is located on CD177. The HNA-3 antigen system has two antigens (3a and 3b) which are located on the seventh exon of the CLT2 gene (SLC44A2). The HNA-4 and HNA-5 antigen systems each have two known antigens (a and b) and are located in the β2 integrin. HNA-4 is located on the αM chain (CD11b) and HNA-5 is located on the αL integrin unit (CD11a). [66]

Subpopulations

Activity of neutrophil-killer and neutrophil-cager in NBT test Neutrophil subpopulation.svg
Activity of neutrophil-killer and neutrophil-cager in NBT test

Two functionally unequal subpopulations of neutrophils were identified on the basis of different levels of their reactive oxygen metabolite generation, membrane permeability, activity of enzyme system, and ability to be inactivated. The cells of one subpopulation with high membrane permeability (neutrophil-killers) intensively generate reactive oxygen metabolites and are inactivated in consequence of interaction with the substrate, whereas cells of another subpopulation (neutrophil-cagers) produce reactive oxygen species less intensively, don't adhere to substrate and preserve their activity. [67] [68] [69] [70] [71] Additional studies have shown that lung tumors can be infiltrated by various populations of neutrophils. [72]

Video

Neutrophils display highly directional amoeboid motility in infected footpad and phalanges. Intravital imaging was performed in the footpad path of LysM-eGFP mice 20 minutes after infection with Listeria monocytogenes . [73]

Additional images

See also

Related Research Articles

<span class="mw-page-title-main">Immune system</span> Biological system protecting an organism against disease

The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.

<span class="mw-page-title-main">Inflammation</span> Physical effects resulting from activation of the immune system

Inflammation is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and initiate tissue repair.

<span class="mw-page-title-main">Macrophage</span> Type of white blood cell

Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

<span class="mw-page-title-main">Phagocytosis</span> Process by which a cell uses its plasma membrane to engulf a large particle

Phagocytosis is the process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is called a phagocyte.

<span class="mw-page-title-main">CD32</span> Surface receptor glycoprotein

CD32, also known as FcγRII or FCGR2, is a surface receptor glycoprotein belonging to the Ig gene superfamily. CD32 can be found on the surface of a variety of immune cells. CD32 has a low-affinity for the Fc region of IgG antibodies in monomeric form, but high affinity for IgG immune complexes. CD32 has two major functions: cellular response regulation, and the uptake of immune complexes. Cellular responses regulated by CD32 include phagocytosis, cytokine stimulation, and endocytic transport. Dysregulated CD32 is associated with different forms of autoimmunity, including systemic lupus erythematosus. In humans, there are three major CD32 subtypes: CD32A, CD32B, and CD32C. While CD32A and CD32C are involved in activating cellular responses, CD32B is inhibitory.

<span class="mw-page-title-main">Phagocyte</span> Cells that ingest harmful matter within the body

Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.

<span class="mw-page-title-main">Monocyte</span> Subtype of leukocytes

Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also influence adaptive immune responses and exert tissue repair functions. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.

<span class="mw-page-title-main">Granulocyte</span> Category of white blood cells

Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that is, they have varying shapes (morphology) of the nucleus ; and are referred to as polymorphonuclear leukocytes. In common terms, polymorphonuclear granulocyte refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types have varying morphology. Granulocytes are produced via granulopoiesis in the bone marrow.

<span class="mw-page-title-main">Myeloperoxidase deficiency</span> Medical condition

Myeloperoxidase deficiency is a disorder featuring lack in either the quantity or the function of myeloperoxidase–an iron-containing protein expressed primarily in neutrophil granules. There are two types of myeloperoxidase deficiency: primary/inherited and secondary/acquired. Lack of functional myeloperoxidase leads to less efficient killing of intracellular pathogens, particularly Candida albicans, as well as less efficient production and release of neutrophil extracellular traps (NETs) from the neutrophils to trap and kill extracellular pathogens. Despite these characteristics, more than 95% of individuals with myeloperoxidase deficiency experience no symptoms in their lifetime. For those who do experience symptoms, the most common symptom is frequent infections by Candida albicans. Individuals with myeloperoxidase deficiency also experience higher rates of chronic inflammatory conditions. Myeloperoxidase deficiency is diagnosed using flow cytometry or cytochemical stains. There is no treatment for myeloperoxidase deficiency itself. Rather, in the rare cases that individuals experience symptoms, these infections should be treated.

Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed by phagocytes. Different types of things ("targets") can be tagged by opsonins for phagocytosis, including: pathogens, cancer cells, aged cells, dead or dying cells, excess synapses, or protein aggregates. Opsonins help clear pathogens, as well as dead, dying and diseased cells.

<span class="mw-page-title-main">Phagosome</span>

In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).

<span class="mw-page-title-main">Innate immune system</span> Immunity strategy in living beings

The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates.

<span class="mw-page-title-main">Fc receptor</span> Surface protein important to the immune system

In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.

<span class="mw-page-title-main">Complement component 5a</span> Protein fragment

C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b fragments. C5b is important in late events of the complement cascade, an orderly series of reactions which coordinates several basic defense mechanisms, including formation of the membrane attack complex (MAC), one of the most basic weapons of the innate immune system, formed as an automatic response to intrusions from foreign particles and microbial invaders. It essentially pokes microscopic pinholes in these foreign objects, causing loss of water and sometimes death. C5a, the other cleavage product of C5, acts as a highly inflammatory peptide, encouraging complement activation, formation of the MAC, attraction of innate immune cells, and histamine release involved in allergic responses. The origin of C5 is in the hepatocyte, but its synthesis can also be found in macrophages, where it may cause local increase of C5a. C5a is a chemotactic agent and an anaphylatoxin; it is essential in the innate immunity but it is also linked with the adaptive immunity. The increased production of C5a is connected with a number of inflammatory diseases.

<span class="mw-page-title-main">Neutrophil extracellular traps</span> Networks of fibres which bind pathogens

Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens. Neutrophils are the immune system's first line of defense against infection and have conventionally been thought to kill invading pathogens through two strategies: engulfment of microbes and secretion of anti-microbials. In 2004, a novel third function was identified: formation of NETs. NETs allow neutrophils to kill extracellular pathogens while minimizing damage to the host cells. Upon in vitro activation with the pharmacological agent phorbol myristate acetate (PMA), Interleukin 8 (IL-8) or lipopolysaccharide (LPS), neutrophils release granule proteins and chromatin to form an extracellular fibril matrix known as NET through an active process.

<span class="mw-page-title-main">C3b</span>

C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B, or a C5 convertase when bound to C4b and C2b or when an additional C3b molecule binds to the C3bBb complex.

CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, macrophages, and certain T cells. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16.

<span class="mw-page-title-main">ICAM3</span> Mammalian protein found in Homo sapiens

Intercellular adhesion molecule 3 (ICAM3) also known as CD50, is a protein that in humans is encoded by the ICAM3 gene. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.

A non-specific immune cell is an immune cell that responds to many antigens, not just one antigen. Non-specific immune cells function in the first line of defense against infection or injury. The innate immune system is always present at the site of infection and ready to fight the bacteria; it can also be referred to as the "natural" immune system. The cells of the innate immune system do not have specific responses and respond to each foreign invader using the same mechanism.

Chemorepulsion is the directional movement of a cell away from a substance. Of the two directional varieties of chemotaxis, chemoattraction has been studied to a much greater extent. Only recently have the key components of the chemorepulsive pathway been elucidated. The exact mechanism is still being investigated, and its constituents are currently being explored as likely candidates for immunotherapies.

References

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  2. ↑ Ermert D, Niemiec MJ, Röhm M, Glenthøj A, Borregaard N, Urban CF (August 2013). "Candida albicans escapes from mouse neutrophils". Journal of Leukocyte Biology. 94 (2): 223–236. doi:10.1189/jlb.0213063. PMID   23650619. S2CID   25619835.
  3. ↑ Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L (May 2000). "Neutrophils: molecules, functions and pathophysiological aspects". Laboratory Investigation; A Journal of Technical Methods and Pathology. 80 (5): 617–653. doi: 10.1038/labinvest.3780067 . PMID   10830774. S2CID   22536645.
  4. ↑ Klebanoff SJ, Clark RA (1978). The Neutrophil: Function and Clinical Disorders. Elsevier/North-Holland Amsterdam. ISBN   978-0-444-80020-6.
  5. ↑ Nathan C (March 2006). "Neutrophils and immunity: challenges and opportunities". Nature Reviews. Immunology. 6 (3): 173–182. doi:10.1038/nri1785. PMID   16498448. S2CID   1590558.
  6. ↑ Welsh, Charles J. (2021). Hole's Essentials of Human Anatomy and Physiology (14 ed.). New York, USA: McGraw Hill. p. 336. ISBN   978-1-260-57521-7 . Retrieved 28 February 2023.
  7. ↑ Jacobs L, Nawrot TS, de Geus B, Meeusen R, Degraeuwe B, Bernard A, et al. (October 2010). "Subclinical responses in healthy cyclists briefly exposed to traffic-related air pollution: an intervention study". Environmental Health. 9 (64): 64. Bibcode:2010EnvHe...9...64J. doi: 10.1186/1476-069X-9-64 . PMC   2984475 . PMID   20973949.
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