Innate immune system: Difference between revisions

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{{shortShort description|OneImmunity ofstrategy thein twoliving main immunity strategiesbeings}}

{{Update|date=March 2024}}

{{More citations needed|date=March 2024}}

[[File:Innate immune system.png|thumb|Innate immune system]]

The '''innate, immune system''' or '''nonspecific, immune system'''<ref>{{Cite web|title=Immune response: MedlinePlus Medical Encyclopedia|url=https://medlineplus.gov/ency/article/000821.htm|access-date=2021-11-07|website=medlineplus.gov|language=en}}</ref> is one of the two main immunity strategies in [[vertebrate]]s (the other being the [[adaptive immune system]]) in [[vertebrate]]s. The innate immune system is an alternate defense strategy and is the dominant immune system response found in [[plant]]s, [[fungi]], [[insectprokaryote]]s, and primitive [[multicellular organismsinvertebrate]]s (see [[#Beyond{{Section vertebrateslink||Beyond vertebrates]]}}).<ref name="Janeway">{{cite book | vauthors = Janeway C, Paul C, Travers M, Walport M, Shlomchik M | author-link = Charles Janeway | title = Immunobiology | edition = Fifth | publisher = Garland Science | year = 2001 | ___location = New York and London| url = https://www.ncbi.nlm.nih.gov/books/bv.fcgiNBK10757/?call=bv.View..ShowTOC&rid=imm.TOC&depth=10| isbn = 0-8153-4101-6}}.</ref>

The major functions of the innate immune system are to:

* recruit immune cells to infection sites by producing chemical factors, including chemical mediators called [[cytokine]]s

* activate the [[complement cascade]] to identify [[bacteria]], activate cells, and promote clearance of [[immune complex|antibody complexes]] or dead cells

* identify and remove foreign substances present in organs, tissues, blood and [[lymph]], by specialized [[white blood cellscell]]s

* activate the [[adaptive immune system]] through [[antigen presentation]]

* act as a physical and chemical barrier to infectious agents; via physical measures such as skin and mucus, and chemical measures such as [[Coagulation|clotting factorsfactor]]s in blood, which are released following a contusion or other injury that breaks through the first-line physical barrier (not to be confused with a second-line physical or chemical barrier, such as theand [[blood–brainhost barrier]],defence which protects the nervous system from [[pathogenspeptide]] that have already gained access to the host)s.

{{Toclimit|3}}

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! Anatomical barrier !! Additional defense mechanisms

|-

| [[Skin]] || Sweat (including [[dermcidin]]), [[cathelicidin]], desquamation, flushing,<ref name=Mayer/> organic acids,<ref name=Mayer/> [[skin flora]]

|-

| [[Gastrointestinal tract]] || [[Peristalsis]], [[gastric acid]], [[bile acid]]s, [[digestive enzyme]],<br> flushing, [[thiocyanate]],<ref name=Mayer/> [[defensin]]s,<ref name=Mayer/> [[gut flora]],<ref name=Mayer/> [[lysozyme]]s

|-

| [[Respiratory airways]] and [[lungs]] || Mucociliary escalator,<ref>{{cite web | url = https://medical-dictionary.thefreedictionary.com/mucociliary+escalator | title = Mucociliary escalator. | work = Saunders Comprehensive Veterinary Dictionary | edition = 3rd | date = 2007 | publisher = Elsevier, Inc. | access-date = 11 June 2018 }}</ref> [[Pulmonary surfactant|surfactant]],<ref name=Mayer/> [[defensins]]<ref name=Mayer/>

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==Complement system==

{{main|Complement system}}

The [[complement system]] is a [[biochemical cascade]] of the immune system that helps, or “complements”"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:

* trigger the recruitment of inflammatory cells

* "tag" pathogens for destruction by other cells by [[Opsonin|''opsonizing'']], or coating, the surface of the pathogen

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{{See also|Nonspecific immune cell#Cells of the innate immune system|l1=Cells of the innate immune system}}

[[File:SEM blood cells.jpg|thumb|right|230px|A [[scanning electron microscope]] image of normal circulating human blood. One can see red blood cells, several knobby white blood cells including [[#Cells of the Adaptive Immune System|lymphocytes]], a [[#Macrophages|monocyte]], a [[#Neutrophils|neutrophil]], and many small disc-shape [[platelet]]s.]]

White blood cells (WBCs) are also known as [[leukocyte]]s. 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 [[macrophage]]s, [[mast cell]]s, and [[dendritic cell]]s 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 cell]]s present in [[bone marrow]].<ref name="Monga">{{cite journal | vauthors = Monga I, Kaur K, Dhanda S| title = Revisiting hematopoiesis: applications of the bulk and single-cell transcriptomics dissecting transcriptional heterogeneity in hematopoietic stem cells | journal = Briefings in Functional Genomics | volume = 21 | issue = 3 | pages = 159–176 | date = March 2022 | pmid = 35265979 | doi = 10.1093/bfgp/elac002}}</ref><ref name="Alberts">{{cite book| vauthors =Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walters P| title = Molecular Biology of the Cell | edition = Fourth | url = https://www.ncbi.nlm.nih.gov/books/bv.fcgiNBK21054/?call=bv.View..ShowTOC&rid=mboc4.TOC&depth=2| year = 2002| publisher = Garland Science| ___location = New York and London| isbn = 0815332181 }}</ref>

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.<ref name="Janeway" />

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The word 'phagocyte' literally means 'eating cell'. These are immune cells that engulf, or '[[Phagocytosis|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]].<ref name="Janeway"/> 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’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.<ref name=Alberts/> 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. [[File:Macrophage.jpg|thumb|left|150px|A macrophage]]

====Macrophages====

{{main|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 [[monocyte]]s. Macrophages are the most efficient phagocytes and can phagocytose substantial numbers of bacteria or other cells or microbes.<ref name="Janeway"/> 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.<ref name="Janeway"/> There are also resident macrophages in many tissues including mucous membranes, liver, lungs, and skin (where they are often called [[Langerhans cell]]s).

====Neutrophils====

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====Dendritic cells====

{{main|Dendritic cell}}

Dendritic cells (DCs) are phagocytic cells present in tissues that are in contact with the external environment, mainly the [[Human skin|skin]] (where they are often called [[Langerhans cell]]s), and the inner mucosal lining of the [[Human nose|nose]], [[lung]]s, [[stomach]], and [[intestine]]s.<ref name=Alberts/> They are named for their resemblance to [[neuronal]] [[dendrite]]s, 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 system]]s.

[[File:PBEosinophil.jpg|thumb|left|120px|An eosinophil]]

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===Natural killer cells===

{{main|Natural killer cell}}

[[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.<ref name="Janeway6">{{cite book| vauthors = Janeway C |title = Immunobiology |edition = 6th|year = 2005|publisher = Garland Science|isbn = 0-443-07310-4}}</ref> 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.<ref>{{cite journal | vauthors = Arai S, Meagher R, Swearingen M, Myint H, Rich E, Martinson J, Klingemann H | title = Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial | journal = Cytotherapy | volume = 10 | issue = 6 | pages = 625–632 | year = 2008 | pmid = 18836917 | doi = 10.1080/14653240802301872 }}</ref><ref>{{cite journal | vauthors = Tonn T, Becker S, Esser R, Schwabe D, Seifried E | title = Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92 | journal = Journal of Hematotherapy & Stem Cell Research | volume = 10 | issue = 4 | pages = 535–544 | date = August 2001 | pmid = 11522236 | doi = 10.1089/15258160152509145 }}</ref><ref name="pmid8152260">{{cite journal | vauthors = Gong JH, Maki G, Klingemann HG | title = Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells | journal = Leukemia | volume = 8 | issue = 4 | pages = 652–658 | date = April 1994 | pmid = 8152260 }}</ref><ref>{{cite book | vauthors = Klingemann HG | chapter = Development and testing of NK cell lines | veditors = Lotze MT, Thompson AW | title = Natural killer cells - Basic Science and Clinical applications | date = 2010 | pages = 169–175 }}</ref>

===γδ T cells===

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* [[measles]]

* [[rhinovirus]]

|| yes || yes<ref>{{cite journal | vauthors = Agrawal P, Nawadkar R, Ojha H, Kumar J, Sahu A | title = Complement Evasion Strategies of Viruses: An Overview | journal = Frontiers in Microbiology | volume = 8 | pagesarticle-number = 1117 | date = 2017-06-16 | pmid = 28670306 | pmc = 5472698 | doi = 10.3389/fmicb.2017.01117 | doi-access = free }}</ref> || yes

|-

| rowspan="2" | Intracellular '''[[bacteria]]''' ||

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* ''[[Histoplasma]]''

* ''[[Cryptococcus (fungus)|Cryptococcus]]''

|| noyes <ref>{{cite journal | vauthors = Jia LJ, Gonzales K, Orasch T, Schmidt F, Brakhage AA | title = Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities | journal = Nature Microbiology | volume = 9 | pages = 2216–2231 | date = 26 August 2024 | issue = 9 | doi = 10.1038/s41564-024-01780-0 | pmid = 39187614 | doi-access = free }}</ref> || yes || yes<ref>{{cite journal | vauthors = Ma LL, Wang CL, Neely GG, Epelman S, Krensky AM, Mody CH | title = NK cells use perforin rather than granulysin for anticryptococcal activity | journal = Journal of Immunology | volume = 173 | issue = 5 | pages = 3357–3365 | date = September 2004 | pmid = 15322199 | doi = 10.4049/jimmunol.173.5.3357 | s2cid = 43258057 | doi-access = free }}</ref>

|-

|}

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===Plants===

{{Main|Plant disease resistance#Immune system}}

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 [[Phytopathology|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 [[herbivore]]s.<ref name="Plant">{{cite web | vauthors = Schneider D | date = 2005 | url = http://cmgm.stanford.edu/micro/Schneider-lab/Innate%20immunity%20couhjioj[ijio[joij[oi[oimiohuh79-9yrse20course.html | title = Plant immune responses | archive-url = https://web.archive.org/web/20070609165047/http://cmgm.stanford.edu/micro/Schneider-lab/Innate%20immunity%20course.html | archive-date = 9 June 2007 | publisher = Stanford University Department of Microbiology and Immunology }}</ref> (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.<ref name= Plant/>

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)<ref>{{cite journal | vauthors = Song WY, Wang GL, Chen LL, Kim HS, Pi LY, Holsten T, Gardner J, Wang B, Zhai WX, Zhu LH, Fauquet C, Ronald P | display-authors = 6 | title = A receptor kinase-like protein encoded by the rice disease resistance gene, Xa21 | journal = Science | volume = 270 | issue = 5243 | pages = 1804–1806 | date = December 1995 | pmid = 8525370 | doi = 10.1126/science.270.5243.1804 | s2cid = 10548988 | bibcode = 1995Sci...270.1804S | url = https://escholarship.org/uc/item/4x0247kj | url-access = subscription }}</ref><ref>{{cite journal | vauthors = Ronald PC, Beutler B | title = Plant and animal sensors of conserved microbial signatures | journal = Science | volume = 330 | issue = 6007 | pages = 1061–1064 | date = November 2010 | pmid = 21097929 | doi = 10.1126/science.1189468 | s2cid = 18311102 | bibcode = 2010Sci...330.1061R | url = https://escholarship.org/uc/item/9q96r8gz }}</ref> and in ''[[Arabidopsis]]'' ([[FLS2]], 2000).<ref>{{cite journal | vauthors = Gómez-Gómez L, Boller T | title = FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis | journal = Molecular Cell | volume = 5 | issue = 6 | pages = 1003–1011 | date = June 2000 | pmid = 10911994 | doi = 10.1016/S1097-2765(00)80265-8 | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Rojo E, Martín R, Carter C, Zouhar J, Pan S, Plotnikova J, Jin H, Paneque M, Sánchez-Serrano JJ, Baker B, Ausubel FM, Raikhel NV | display-authors = 6 | title = VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens | journal = Current Biology | volume = 14 | issue = 21 | pages = 1897–1906 | date = November 2004 | pmid = 15530390 | doi = 10.1016/j.cub.2004.09.056 | s2cid = 3231431 | doi-access = free | bibcode = 2004CBio...14.1897R }}</ref>

"Resistance" (R) proteins, encoded by [[R gene]]s, are widely present in plants and detect pathogens. These proteins contain domains similar to the [[NOD-like receptor|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.<ref>[[Chitosan#Agricultural &and Horticulturalhorticultural use]]</ref> SAR involves the production of [[chemical messenger (disambiguation)|chemical messenger]]s, 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.<ref>{{cite journal | vauthors = Linden JC, Stoner RJ, Knutson KW, Gardner-Hughes CA | title = Organic disease control elicitors. | journal = Agro Food Industry Hi-Tech | date = 2000 | volume = 11 | issue = 5 | pages = 32–34 | url=http://www.yeacrops.com/Crop%20Protection%20Article.pdf| url-status=dead| archive-url= https://web.archive.org/web/20070706111024/http://www.yeacrops.com/Crop%20Protection%20Article.pdf| archive-date=6 July 2007| df=dmy-all }}</ref> 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 interference|RNA silencing]] mechanisms are important in the plant systemic response, as they can block virus replication.<ref>{{cite journal | vauthors = Baulcombe D | title = RNA silencing in plants | journal = Nature | volume = 431 | issue = 7006 | pages = 356–363 | date = September 2004 | pmid = 15372043 | doi = 10.1038/nature02874 | s2cid = 4421274 | bibcode = 2004Natur.431..356B }}</ref> The ''[[jasmonic acid]] response'' is stimulated in leaves damaged by insects, and involves the production of [[methyl jasmonate]].<ref name= Plant/>

== See also ==

* [[Antimicrobial peptides]]

* [[Apoptosis]]

* [[Innate lymphoid cell]]

* [[NOD-like receptor]]

* [[Endothelial cell tropism]]

* [[Selnoflast]]

== References ==