Innate immune system

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Innate immune system

The innate immune system or nonspecific immune system [1] is one of the two main immunity strategies (the other being the adaptive immune system) 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 (see Beyond vertebrates). [2]

Contents

The major functions of the innate immune system are to:

Anatomical barriers

Anatomical barriers include physical, chemical and biological barriers. The epithelial surfaces form a physical barrier that is impermeable to most infectious agents, acting as the first line of defense against invading organisms. [3] Desquamation (shedding) of skin epithelium also helps remove bacteria and other infectious agents that have adhered to the epithelial surface. Lack of blood vessels, the inability of the epidermis to retain moisture, and the presence of sebaceous glands in the dermis, produces an environment unsuitable for the survival of microbes. [3] In the gastrointestinal and respiratory tract, movement due to peristalsis or cilia, respectively, helps remove infectious agents. [3] Also, mucus traps infectious agents. [3] Gut flora can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or cell surface attachment sites. [3] The flushing action of tears and saliva helps prevent infection of the eyes and mouth. [3]

Anatomical barrierAdditional defense mechanisms
Skin Sweat (including dermcidin), cathelicidin, desquamation, flushing, [3] organic acids, [3] skin flora
Gastrointestinal tract Peristalsis, gastric acid, bile acids, digestive enzyme,
flushing, thiocyanate, [3] defensins, [3] gut flora, [3] lysozymes
Respiratory airways and lungs Mucociliary escalator, [4] surfactant, [3] defensins [3]
Nasopharynx Mucus, saliva, lysozyme [3]
Eyes Tears [3]
Blood–brain barrier endothelial cells (via passive diffusion/ osmosis & active selection). P-glycoprotein (mechanism by which active transportation is mediated)

Inflammation

Inflammation is one of the first responses of the immune system to infection or irritation. Inflammation is stimulated by chemical factors released by injured cells. It establishes a physical barrier against the spread of infection and promotes healing of any damaged tissue following pathogen clearance. [5]

The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells, and mast cells. These cells present receptors contained on the surface or within the cell, named pattern recognition receptors (PRRs), which recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRRs recognizes a PAMP) and release inflammatory mediators, like cytokines and chemokines, which are responsible for the clinical signs of inflammation. PRR activation and its cellular consequences have been well-characterized as methods of inflammatory cell death, which include pyroptosis, necroptosis, and PANoptosis. These cell death pathways help clear infected or aberrant cells and release cellular contents and inflammatory mediators.

Chemical factors produced during inflammation (histamine, bradykinin, serotonin, leukotrienes, and prostaglandins) sensitize pain receptors, cause local vasodilation of the blood vessels, and attract phagocytes, especially neutrophils. [5] Neutrophils then trigger other parts of the immune system by releasing factors that summon additional leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF, HMGB1, and IL-1. [6]

The inflammatory response is characterized by the following symptoms:

Complement system

The complement system is a biochemical cascade of the immune system that helps, or "complements", the ability of antibodies to clear pathogens or mark them for destruction by other cells. The cascade is composed of many plasma proteins, synthesized in the liver, primarily by hepatocytes. The proteins work together to:

The three different complement systems are classical, alternative and lectin.

Elements of the complement cascade can be found in many non-mammalian species including plants, birds, fish, and some species of invertebrates. [7]

White blood cells

A scanning electron microscope image of normal circulating human blood. One can see red blood cells, several knobby white blood cells including lymphocytes, a monocyte, a neutrophil, and many small disc-shape platelets. SEM blood cells.jpg
A scanning electron microscope image of normal circulating human blood. One can see red blood cells, several knobby white blood cells including lymphocytes, a monocyte, a neutrophil, and many small disc-shape platelets.

White blood cells (WBCs) are also known as leukocytes. Most leukocytes differ from other cells of the body in that they are not tightly associated with a particular organ or tissue; thus, their function is similar to that of independent, single-cell organisms. Most leukocytes are able to move freely and interact with and capture cellular debris, foreign particles, and invading microorganisms (although macrophages, mast cells, and dendritic cells are less mobile). Unlike many other cells, most innate immune leukocytes cannot divide or reproduce on their own, but are the products of multipotent hematopoietic stem cells present in bone marrow. [8] [9]

The innate leukocytes include: natural killer cells, mast cells, eosinophils, basophils; and the phagocytic cells include macrophages, neutrophils, and dendritic cells, and function within the immune system by identifying and eliminating pathogens that might cause infection. [2]

Mast cells

Mast cells are a type of innate immune cell that resides in connective tissue and in mucous membranes. They are intimately associated with wound healing and defense against pathogens, but are also often associated with allergy and anaphylaxis. [5] When activated, mast cells rapidly release characteristic granules, rich in histamine and heparin, along with various hormonal mediators and chemokines, or chemotactic cytokines into the environment. Histamine dilates blood vessels, causing the characteristic signs of inflammation, and recruits neutrophils and macrophages. [5]

Phagocytes

The word 'phagocyte' literally means 'eating cell'. These are immune cells that engulf, or 'phagocytose', pathogens or particles. To engulf a particle or pathogen, a phagocyte extends portions of its plasma membrane, wrapping the membrane around the particle until it is enveloped (i.e., the particle is now inside the cell). Once inside the cell, the invading pathogen is contained inside a phagosome, which merges with a lysosome. [2] The lysosome contains enzymes and acids that kill and digest the particle or organism. In general, phagocytes patrol the body searching for pathogens, but are also able to react to a group of highly specialized molecular signals produced by other cells, called cytokines. The phagocytic cells of the immune system include macrophages, neutrophils, and dendritic cells.

Phagocytosis of the hosts' own cells is common as part of regular tissue development and maintenance. When host cells die, either by apoptosis or by cell injury due to an infection, phagocytic cells are responsible for their removal from the affected site. [9] By helping to remove dead cells preceding growth and development of new healthy cells, phagocytosis is an important part of the healing process following tissue injury.

A macrophage Macrophage.jpg
A macrophage

Macrophages

Macrophages, from the Greek, meaning "large eaters", are large phagocytic leukocytes, which are able to move beyond the vascular system by migrating through the walls of capillary vessels and entering the areas between cells in pursuit of invading pathogens. In tissues, organ-specific macrophages are differentiated from phagocytic cells present in the blood called monocytes. Macrophages are the most efficient phagocytes and can phagocytose substantial numbers of bacteria or other cells or microbes. [2] The binding of bacterial molecules to receptors on the surface of a macrophage triggers it to engulf and destroy the bacteria through the generation of a "respiratory burst", causing the release of reactive oxygen species. Pathogens also stimulate the macrophage to produce chemokines, which summon other cells to the site of infection. [2]

Neutrophils

A neutrophil PBNeutrophil.jpg
A neutrophil

Neutrophils, along with eosinophils and basophils, are known as granulocytes due to the presence of granules in their cytoplasm, or as polymorphonuclear cells (PMNs) due to their distinctive lobed nuclei. Neutrophil granules contain a variety of toxic substances that kill or inhibit growth of bacteria and fungi. Similar to macrophages, neutrophils attack pathogens by activating a respiratory burst. The main products of the neutrophil respiratory burst are strong oxidizing agents including hydrogen peroxide, free oxygen radicals and hypochlorite. Neutrophils are the most abundant type of phagocyte, normally representing 50–60% of the total circulating leukocytes, and are usually the first cells to arrive at the site of an infection. [5] The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day, and more than 10 times that many per day during acute inflammation. [5]

Dendritic cells

Dendritic cells (DCs) are phagocytic cells present in tissues that are in contact with the external environment, mainly the skin (where they are often called Langerhans cells), and the inner mucosal lining of the nose, lungs, stomach, and intestines. [9] They are named for their resemblance to neuronal dendrites, but dendritic cells are not connected to the nervous system. Dendritic cells are very important in the process of antigen presentation, and serve as a link between the innate and adaptive immune systems.

An eosinophil PBEosinophil.jpg
An eosinophil

Basophils and eosinophils

Basophils and eosinophils are cells related to the neutrophil. When activated by a pathogen encounter, histamine-releasing basophils are important in the defense against parasites and play a role in allergic reactions, such as asthma. [2] Upon activation, eosinophils secrete a range of highly toxic proteins and free radicals that are highly effective in killing parasites, but may also damage tissue during an allergic reaction. Activation and release of toxins by eosinophils are, therefore, tightly regulated to prevent any inappropriate tissue destruction. [5]

Natural killer cells

Natural killer cells (NK cells) do not directly attack invading microbes. Rather, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells, recognizing such cells by a condition known as "missing self". This term describes cells with abnormally low levels of a cell-surface marker called MHC I (major histocompatibility complex) - a situation that can arise in viral infections of host cells. [10] They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self". The MHC makeup on the surface of damaged cells is altered and the NK cells become activated by recognizing this. Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens. Those MHC antigens are recognized by killer cell immunoglobulin receptors (KIR) that slow the reaction of NK cells. The NK-92 cell line does not express KIR and is developed for tumor therapy. [11] [12] [13] [14]

γδ T cells

Like other 'unconventional' T cell subsets bearing invariant T cell receptors (TCRs), such as CD1d-restricted Natural Killer T cells, γδ T cells exhibit characteristics that place them at the border between innate and adaptive immunity. γδ T cells may be considered a component of adaptive immunity in that they rearrange TCR genes to produce junctional diversity and develop a memory phenotype. The various subsets may be considered part of the innate immune system where a restricted TCR or NK receptors may be used as a pattern recognition receptor. For example, according to this paradigm, large numbers of Vγ9/Vδ2 T cells respond within hours to common molecules produced by microbes, and highly restricted intraepithelial Vδ1 T cells will respond to stressed epithelial cells.

Other vertebrate mechanisms

The coagulation system overlaps with the immune system. Some products of the coagulation system can contribute to non-specific defenses via their ability to increase vascular permeability and act as chemotactic agents for phagocytic cells. In addition, some of the products of the coagulation system are directly antimicrobial. For example, beta-lysine, a protein produced by platelets during coagulation, can cause lysis of many Gram-positive bacteria by acting as a cationic detergent. [3] Many acute-phase proteins of inflammation are involved in the coagulation system.

Increased levels of lactoferrin and transferrin inhibit bacterial growth by binding iron, an essential bacterial nutrient. [3]

Neural regulation

The innate immune response to infectious and sterile injury is modulated by neural circuits that control cytokine production period. The inflammatory reflex is a prototypical neural circuit that controls cytokine production in the spleen. [15] Action potentials transmitted via the vagus nerve to the spleen mediate the release of acetylcholine, the neurotransmitter that inhibits cytokine release by interacting with alpha7 nicotinic acetylcholine receptors (CHRNA7) expressed on cytokine-producing cells. [16] The motor arc of the inflammatory reflex is termed the cholinergic anti-inflammatory pathway.

Pathogen-specificity

The parts of the innate immune system display specificity for different pathogens.

PathogenMain examples [17] Phagocytosis [17] complement [17] NK cells [17]
Intracellular and cytoplasmic virus yesyes [18] yes
Intracellular bacteria yes (specifically neutrophils)yes [19] yes
noyesyes
Extracellular bacteria yesyesno
Intracellular protozoa nonoyes
Extracellular protozoa yesyesno/yes
Extracellular fungi noyesyes [20]

Immune evasion

Innate immune system cells prevent free growth of microorganisms within the body, but many pathogens have evolved mechanisms to evade it. [21] [22]

One strategy is intracellular replication, as practised by Mycobacterium tuberculosis , or wearing a protective capsule, which prevents lysis by complement and by phagocytes, as in Salmonella . [23] Bacteroides species are normally mutualistic bacteria, making up a substantial portion of the mammalian gastrointestinal flora. [24] Species such as B. fragilis are opportunistic pathogens, causing infections of the peritoneal cavity. They inhibit phagocytosis by affecting the phagocytes receptors used to engulf bacteria. They may also mimic host cells so the immune system does not recognize them as foreign. Staphylococcus aureus inhibits the ability of the phagocyte to respond to chemokine signals. M. tuberculosis , Streptococcus pyogenes , and Bacillus anthracis utilize mechanisms that directly kill the phagocyte.[ citation needed ]

Bacteria and fungi may form complex biofilms, protecting them from immune cells and proteins; biofilms are present in the chronic Pseudomonas aeruginosa and Burkholderia cenocepacia infections characteristic of cystic fibrosis. [25]

Viruses

Type I interferons (IFN), secreted mainly by dendritic cells, [26] play a central role in antiviral host defense and a cell's antiviral state. [27] Viral components are recognized by different receptors: Toll-like receptors are located in the endosomal membrane and recognize double-stranded RNA (dsRNA), MDA5 and RIG-I receptors are located in the cytoplasm and recognize long dsRNA and phosphate-containing dsRNA respectively. [28] When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) and the CARD-containing adaptor MAVS changes. In parallel, when TLRs in the endocytic compartments recognize a virus the activation of the adaptor protein TRIF is induced. Both pathways converge in the recruitment and activation of the IKKε/TBK-1 complex, inducing dimerization of transcription factors IRF3 and IRF7, which are translocated in the nucleus, where they induce IFN production with the presence of a particular transcription factor and activate transcription factor 2. IFN is secreted through secretory vesicles, where it can activate receptors on both the cell it was released from (autocrine) or nearby cells (paracrine). This induces hundreds of interferon-stimulated genes to be expressed. This leads to antiviral protein production, such as protein kinase R, which inhibits viral protein synthesis, or the 2′,5′-oligoadenylate synthetase family, which degrades viral RNA. [27]

Some viruses evade this by producing molecules that interfere with IFN production. For example, the Influenza A virus produces NS1 protein, which can bind to host and viral RNA, interact with immune signaling proteins or block their activation by ubiquitination, thus inhibiting type I IFN production. [29] Influenza A also blocks protein kinase R activation and establishment of the antiviral state. [30] The dengue virus also inhibits type I IFN production by blocking IRF-3 phosophorylation using NS2B3 protease complex. [31]

Beyond vertebrates

Prokaryotes

Bacteria (and perhaps other prokaryotic organisms), utilize a unique defense mechanism, called the restriction modification system to protect themselves from pathogens, such as bacteriophages. In this system, bacteria produce enzymes, called restriction endonucleases, that attack and destroy specific regions of the viral DNA of invading bacteriophages. Methylation of the host's own DNA marks it as "self" and prevents it from being attacked by endonucleases. [32] Restriction endonucleases and the restriction modification system exist exclusively in prokaryotes. [33]

Invertebrates

Invertebrates do not possess lymphocytes or an antibody-based humoral immune system, and it is likely that a multicomponent, adaptive immune system arose with the first vertebrates. [34] Nevertheless, invertebrates possess mechanisms that appear to be precursors of these aspects of vertebrate immunity. Pattern recognition receptors (PRRs) are proteins used by nearly all organisms to identify molecules associated with microbial pathogens. TLRs are a major class of pattern recognition receptor, that exists in all coelomates (animals with a body-cavity), including humans. [35] The complement system exists in most life forms. Some invertebrates, including various insects, crabs, and worms utilize a modified form of the complement response known as the prophenoloxidase (proPO) system. [34]

Antimicrobial peptides are an evolutionarily conserved component of the innate immune response found among all classes of life and represent the main form of invertebrate systemic immunity. Several species of insect produce antimicrobial peptides known as defensins and cecropins .

Proteolytic cascades

In invertebrates, PRRs trigger proteolytic cascades that degrade proteins and control many of the mechanisms of the innate immune system of invertebrates—including hemolymph coagulation and melanization. Proteolytic cascades are important components of the invertebrate immune system because they are turned on more rapidly than other innate immune reactions because they do not rely on gene changes. Proteolytic cascades function in both vertebrate and invertebrates, even though different proteins are used throughout the cascades. [36]

Clotting mechanisms

In the hemolymph, which makes up the fluid in the circulatory system of arthropods, a gel-like fluid surrounds pathogen invaders, similar to the way blood does in other animals. Various proteins and mechanisms are involved in invertebrate clotting. In crustaceans, transglutaminase from blood cells and mobile plasma proteins make up the clotting system, where the transglutaminase polymerizes 210 kDa subunits of a plasma-clotting protein. On the other hand, in the horseshoe crab clotting system, components of proteolytic cascades are stored as inactive forms in granules of hemocytes, which are released when foreign molecules, like lipopolysaccharides enter. [36]

Plants

Members of every class of pathogen that infect humans also infect plants. Although the exact pathogenic species vary with the infected species, bacteria, fungi, viruses, nematodes, and insects can all cause plant disease. As with animals, plants attacked by insects or other pathogens use a set of complex metabolic responses that lead to the formation of defensive chemical compounds that fight infection or make the plant less attractive to insects and other herbivores. [37] (see: plant defense against herbivory).

Like invertebrates, plants neither generate antibody or T-cell responses nor possess mobile cells that detect and attack pathogens. In addition, in case of infection, parts of some plants are treated as disposable and replaceable, in ways that few animals can. Walling off or discarding a part of a plant helps stop infection spread. [37]

Most plant immune responses involve systemic chemical signals sent throughout a plant. Plants use PRRs to recognize conserved microbial signatures. This recognition triggers an immune response. The first plant receptors of conserved microbial signatures were identified in rice (XA21, 1995) [38] [39] and in Arabidopsis (FLS2, 2000). [40] Plants also carry immune receptors that recognize variable pathogen effectors. These include the NBS-LRR class of proteins. When a part of a plant becomes infected with a microbial or viral pathogen, in case of an incompatible interaction triggered by specific elicitors, the plant produces a localized hypersensitive response (HR), in which cells at the site of infection undergo rapid apoptosis to prevent spread to other parts of the plant. HR has some similarities to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine protease that regulates cell disassembly during cell death. [41]

"Resistance" (R) proteins, encoded by R genes, are widely present in plants and detect pathogens. These proteins contain domains similar to the NOD Like Receptors and TLRs. Systemic acquired resistance (SAR) is a type of defensive response that renders the entire plant resistant to a broad spectrum of infectious agents. [42] SAR involves the production of chemical messengers, such as salicylic acid or jasmonic acid. Some of these travel through the plant and signal other cells to produce defensive compounds to protect uninfected parts, e.g., leaves. [43] Salicylic acid itself, although indispensable for expression of SAR, is not the translocated signal responsible for the systemic response. Recent evidence indicates a role for jasmonates in transmission of the signal to distal portions of the plant. RNA silencing mechanisms are important in the plant systemic response, as they can block virus replication. [44] The jasmonic acid response is stimulated in leaves damaged by insects, and involves the production of methyl jasmonate. [37]

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. The five cardinal signs are heat, pain, redness, swelling, and loss of function.

An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellular bacteria, protozoa, helminths, and fungi which could cause serious problems to the health of the host organism if not cleared from the body.

<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">Neutrophil</span> Most abundant type of granulocytes and the most abundant white blood cell

Neutrophils 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. They form an essential part of the innate immune system, with their functions varying in different animals.

<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">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">Cell-mediated immunity</span> Immune response that does not involve antibodies

Cellular immunity, also known as cell-mediated immunity, is an immune response that does not rely on the production of antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.

<span class="mw-page-title-main">Chemokine</span> Small cytokines or signaling proteins secreted by cells

Chemokines, or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.

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">Adaptive immune system</span> Subsystem of the immune system

The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.

Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed mainly by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils, as well as by epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or death. They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. PRRs also mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines.

<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">Alveolar macrophage</span>

An alveolar macrophage, pulmonary macrophage, is a type of macrophage, a professional phagocyte, found in the airways and at the level of the alveoli in the lungs, but separated from their walls.

<span class="mw-page-title-main">Toll-like receptor 6</span> Protein found in humans

Toll-like receptor 6 is a protein that in humans is encoded by the TLR6 gene. TLR6 is a transmembrane protein, member of toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. TLR6 acts in a heterodimer form with toll-like receptor 2 (TLR2). Its ligands include multiple diacyl lipopeptides derived from gram-positive bacteria and mycoplasma and several fungal cell wall saccharides. After dimerizing with TLR2, the NF-κB intracellular signalling pathway is activated, leading to a pro-inflammatory cytokine production and activation of innate immune response. TLR6 has also been designated as CD286.

<span class="mw-page-title-main">CLEC7A</span> Protein-coding gene in humans

C-type lectin domain family 7 member A or Dectin-1 is a protein that in humans is encoded by the CLEC7A gene. CLEC7A is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with a partial immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid dendritic cells, monocytes, macrophages and B cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.

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.

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid, and non- lymphoid tissues, and rarely in the blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the regular lymphoid morphology, absence of rearranged antigen receptors found on T cells and B cells, and phenotypic markers usually present on myeloid or dendritic cells.

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