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((Short description|Subsystem of the immune system))
((About|human immunity|the same concept in botany|Plant-induced systemic resistance))
((More citations needed|date=March 2024))

[[File:SEM Lymphocyte.jpg|thumb|right|A [[scanning electron microscope]] image of a single human [[lymphocyte]]]]
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 [[pathogen]]s or prevent their growth. The acquired immune system is one of the two main [[immunity (medical)|immunity]] strategies found in [[vertebrate]]s (the other being the [[innate immune system]]).

[[File:Ngram acquired immunity vs. adaptive immunity.png|thumb|upright=1.35|[[Google Ngram]]  of "acquired immunity " vs. "adaptive immunity".  The peak  for "adaptive" in the 1960s reflects its introduction to immunology  by [[Robert A. Good]] and use by colleagues; the explosive increase in the 1990s was correlated with the use of the phrase "innate immunity".]]

Like the innate system, the adaptive immune system includes both [[humoral immunity]] components and [[cell-mediated immunity]] components and destroys invading pathogens. Unlike the [[innate immune system]], which is pre-programmed to react to common broad categories of pathogen, the adaptive immune system is highly specific to each particular pathogen the body has encountered.<ref name=":1">((Cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK279396/ |title=The innate and adaptive immune systems |date=4 August 2016 |publisher=Institute for Quality and Efficiency in Health Care (IQWiG)))</ref>

Adaptive immunity creates [[immunological memory]] after an initial response to a specific pathogen, and leads to an enhanced response to future encounters with that pathogen. [[Antibody|Antibodies]] are a critical part of the adaptive immune system. Adaptive immunity can provide long-lasting protection, sometimes for the person's entire lifetime. For example, someone who recovers from measles is now protected against measles for their lifetime; in other cases it does not provide lifetime protection, as with [[chickenpox]]. This process of adaptive immunity is the basis of [[vaccination]].((cn|date=November 2023))

The cells that carry out the adaptive immune response are white blood cells known as [[lymphocyte]]s. [[B cell]]s and [[T cell]]s, two different types of lymphocytes, carry out the main activities: antibody responses, and cell-mediated immune response. In antibody responses, B cells are activated to secrete [[antibodies]], which are proteins also known as immunoglobulins. Antibodies travel through the bloodstream and bind to the foreign antigen causing it to inactivate, which does not allow the antigen to bind to the host.<ref name="Alberts" /> [[Antigens]] are any substances that elicit the adaptive immune response. Sometimes the adaptive system is unable to distinguish harmful from harmless foreign molecules; the effects of this may be [[allergic rhinitis|hayfever]], [[asthma]], or any other [[allergy]].

In adaptive immunity, pathogen-specific [[Immune receptor|receptors]] are "acquired" during the lifetime of the organism (whereas in innate immunity pathogen-specific receptors are already encoded in the [[genome]]). This acquired response is called "adaptive" because it prepares the body's immune system for future challenges (though it can actually also be [[Maladaptation|maladaptive]] when it results in allergies or [[autoimmunity]]).

The system is highly [[adaptation|adaptable]] because of two factors. First, [[somatic hypermutation]] is a process of accelerated random genetic [[mutation]]s in the antibody-coding genes, which allows antibodies with novel specificity to be created. Second, [[V(D)J recombination]] randomly selects one variable (V), one diversity (D), and one joining (J) region for [[genetic recombination]] and discards the rest, which produces a highly unique combination of antigen-receptor gene segments in each lymphocyte. This mechanism allows a small number of genetic segments to generate a vast number of different antigen receptors, which are then uniquely expressed on each individual [[lymphocyte]]. Since the gene rearrangement leads to an irreversible change in the [[DNA]] of each cell, all [[offspring|progeny]] (offspring) of that cell inherit genes that encode the same receptor specificity, including the [[memory B cell]]s and [[memory T cells]] that are the keys to long-lived specific immunity.

== Naming ==
The term "adaptive" was first used by [[Robert A. Good|Robert Good]] in reference to antibody responses in frogs as a synonym for "acquired immune response" in 1964. Good acknowledged he used the terms as synonyms but explained only that he preferred to use the term "adaptive".  He might have been thinking of the then not implausible theory of antibody formation in which antibodies were plastic and could adapt themselves to the molecular shape of antigens, and/or to the concept of "adaptive enzymes" as described by [[Jacques Monod|Monod]] in bacteria, that is, enzymes whose expression could be induced by their substrates.  The phrase was used almost exclusively by Good and his students and a few other immunologists working with marginal organisms until the 1990s when it became widely used in tandem with the term "innate immunity" which became a popular subject after the discovery of the Toll receptor system in ''Drosophila'', a previously marginal organism for the study of immunology.  The term "adaptive" as used in immunology is problematic as acquired immune responses can be both adaptive and maladaptive in the physiological sense. Indeed, both acquired and innate immune responses can be both adaptive and maladaptive in the evolutionary sense.  Most textbooks today, following the early use by [[Charles Janeway|Janeway]], use "adaptive" almost exclusively and noting in glossaries that the term is synonymous with "acquired".((cn|date=September 2022))

The classic sense of "acquired immunity" came to mean, since [[Susumu Tonegawa|Tonegawa's]] discovery, "antigen-specific immunity mediated by somatic gene rearrangements that create clone-defining antigen receptors". In the last decade, the term "adaptive" has been increasingly applied to another class of immune response not so-far associated with somatic gene rearrangements.  These include expansion of [[Natural killer cell|natural killer]] (NK) cells with so-far unexplained specificity for antigens, expansion of NK cells expressing germ-line encoded receptors, and activation of other innate immune cells to an activated state that confers a short-term "immune memory". In this sense, "adaptive immunity" more closely resembles the concept of "activated state" or "heterostasis", thus returning in sense to the physiological sense of "adaptation" to environmental changes.((cn|date=September 2022))

==Functions==
[[File:Primary immune response 1.png|thumb|Overview of the processes involved in the primary immune response]]
Acquired immunity is triggered in vertebrates when a pathogen evades the innate immune system and (1) generates a threshold level of antigen and (2) generates "stranger" or "danger" signals activating [[dendritic cells]].<ref name=Janeway>((cite book | vauthors = Janeway CA, Travers P, Walport M, Shlomchik MJ | title =Immunobiology |edition=5th | publisher = Garland Science | year = 2001 | location = New York and London| url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=imm.TOC&depth=10| isbn = 0-8153-4101-6))</ref>

The major functions of the acquired immune system include:((cn|date=September 2022))
* Recognition of specific "non-self" antigens in the presence of "self", during the process of [[antigen presentation]].
* Generation of responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells.
* Development of [[#Immunological memory|immunological memory]], in which pathogens are "remembered" through [[memory B cell]]s and [[memory T cell]]s.

In humans, it takes 4–7 days for the adaptive immune system to mount a significant response.<ref>((Cite journal |last1=Charles A Janeway |first1=Jr |last2=Travers |first2=Paul |last3=Walport |first3=Mark |last4=Shlomchik |first4=Mark J. |date=2001 |title=Principles of innate and adaptive immunity |url=https://www.ncbi.nlm.nih.gov/books/NBK27090/ |journal=Immunobiology: The Immune System in Health and Disease. 5th Edition |language=en))</ref>

==Lymphocytes==
((main|Lymphocyte))
T and B [[lymphocytes]] are the cells of the adaptive immune system. The human body has about 2 trillion lymphocytes, which are 20–40% of white blood cells; their total mass is about the same as the [[brain]] or [[liver]]. The peripheral bloodstream contains only 2% of all circulating lymphocytes; the other 98% move within tissues and the [[lymphatic system]], which includes the [[lymph nodes]] and [[spleen]].<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 =4th | publisher = Garland Science| year = 2002 | location = New York and London | url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=mboc4.TOC&depth=2 | isbn = 0-8153-3218-1))</ref> In humans, approximately 1–2% of the lymphocyte pool recirculates each hour to increase the opportunity for the cells to encounter the specific pathogen and antigen that they react to.<ref name=USC>((cite web | url = http://pathmicro.med.sc.edu/book/immunol-sta.htm | title = Microbiology and Immunology On-Line Textbook | publisher = University of South Carolina School of Medicine | archive-url = https://web.archive.org/web/20080902212532/http://pathmicro.med.sc.edu/book/immunol-sta.htm | archive-date = 2 September 2008 | url-status = dead ))</ref>

B cells and T cells are derived from the same [[multipotent hematopoietic stem cell]]s, and look identical to one another until after they are activated. B cells play a large role in the [[humoral immune response]], whereas T cells are intimately involved in [[cell-mediated immune response]]s. In all [[vertebrate]]s except [[Agnatha]], B cells and T cells are produced by stem cells in the bone marrow.<ref name=Janeway6>((cite book | vauthors = Janeway CA, Travers P, Walport M, Shlomchik MJ | title = Immunobiology. | edition = 6th | publisher = Garland Science | year = 2005 | isbn = 0-443-07310-4))</ref> T cell progenitors then migrate from the bone marrow to the [[thymus]], where they develop further.

In an adult animal, the peripheral lymphoid organs contain a mixture of B and T cells in at least three stages of differentiation:((cn|date=July 2023))
* [[naive B cell|Naive B]] and [[naive T cell]]s, which have left the bone marrow or thymus and entered the lymphatic system, but have yet to encounter their matching antigen
* [[T cell#Effector|Effector cells]] that have been activated by their matching antigen, and are actively involved in eliminating a pathogen
* Memory cells, the survivors of past infections

==Antigen presentation==
((main|Antigen presentation))
Acquired immunity relies on the capacity of immune cells to distinguish between the body's own cells and unwanted invaders.
The host's cells express "self" [[antigens]]. These antigens are different from those on the surface of bacteria or on the surface of virus-infected host cells ("non-self" or "foreign" antigens). The acquired immune response is triggered by recognizing foreign antigen in the cellular context of an activated dendritic cell.((cn|date=September 2022))

With the exception of non-nucleated cells (including [[erythrocyte]]s), all cells are capable of presenting antigen through the function of major histocompatibility complex (MHC) molecules.<ref name=Janeway6/> Some cells are specially equipped to present antigen, and to prime naive T cells. [[Dendritic cells]], B-cells, and [[macrophages]] are equipped with special "co-stimulatory" ligands recognized by co-stimulatory receptors on T cells, and are termed professional [[antigen-presenting cells]] (APCs).((cn|date=September 2022))

Several T cells subgroups can be activated by professional APCs, and each type of T cell is specially equipped to deal with each unique toxin or microbial pathogen. The type of T cell activated, and the type of response generated, depends, in part, on the context in which the APC first encountered the antigen.<ref name=Janeway/>

===Exogenous antigens===
[[Image:Antigen presentation.svg|thumb|right|Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells.]]
Dendritic cells engulf [[exogenous]] pathogens, such as bacteria, parasites or toxins in the tissues and then migrate, via [[chemotactic]] signals, to the T cell-enriched lymph nodes. During migration, dendritic cells undergo a process of maturation in which they lose most of their ability to engulf other pathogens, and develop an ability to communicate with T-cells.  The dendritic cell uses [[enzyme]]s to chop the pathogen into smaller pieces, called [[antigen]]s.  In the lymph node, the dendritic cell displays these non-self antigens on its surface by coupling them to a receptor called the [[major histocompatibility complex]], or MHC (also known in humans as [[human leukocyte antigen]] (HLA)). This MHC-antigen complex is recognized by T-cells passing through the lymph node. Exogenous antigens are usually displayed on [[MHC class II]] molecules, which activate [[CD4]]+[[T helper cell]]s.<ref name=Janeway/>

===Endogenous antigens===
[[Endogenous]] antigens are produced by intracellular bacteria and viruses replicating within a host cell. The host cell uses enzymes to digest virally associated proteins and displays these pieces on its surface to T-cells by coupling them to MHC. Endogenous antigens are typically displayed on [[MHC class I]] molecules, and activate [[CD8]]+ cytotoxic T-cells. With the exception of non-nucleated cells (including [[erythrocyte]]s), MHC class I is expressed by all host cells.<ref name=Janeway/>

==T lymphocytes==
((main|T cell))

===CD8+ T lymphocytes and cytotoxicity===
((main|Cytotoxic T cell))
Cytotoxic T cells (also known as TC, killer T cell, or cytotoxic T-lymphocyte (CTL)) are a sub-group of T cells that induce the death of cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional.<ref name=Janeway/>

Naive cytotoxic T cells are activated when their T-cell receptor (TCR) strongly interacts with a peptide-bound MHC class I molecule. This affinity depends on the type and orientation of the antigen/MHC complex, and is what keeps the CTL and infected cell bound together.<ref name=Janeway/> Once activated, the CTL undergoes a process called [[clonal selection]], in which it gains functions and divides rapidly to produce an army of "armed" effector cells. Activated CTL then travels throughout the body searching for cells that bear that unique MHC Class I + peptide.((citation needed|date=October 2016))

When exposed to these infected or dysfunctional [[somatic cell]]s, effector CTL release [[perforin]] and [[granulysin]]: cytotoxins that form pores in the target cell's [[plasma membrane]], allowing [[ion]]s and water to flow into the infected cell, and causing it to burst or [[Lysis|lyse]]. CTL release [[granzyme]], a [[serine protease]] encapsulated in a granule that enters cells via pores to induce [[apoptosis]] (cell death). To limit extensive tissue damage during an infection, CTL activation is tightly controlled and in general requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T-cells (see below).<ref name=Janeway/>

On resolution of the infection, most effector cells die and [[phagocyte]]s clear them away—but a few of these cells remain as memory cells.<ref name=Janeway6/> On a later encounter with the same antigen, these memory cells quickly differentiate into effector cells, dramatically shortening the time required to mount an effective response.((citation needed|date=October 2016)) ((clear))

===Helper T-cells===
((main|T helper cell)) [[Image:T cell activation.svg|thumb|upright=1.15|right|The T lymphocyte activation pathway. T&nbsp;cells contribute to immune defenses in two major ways: some direct and regulate immune responses; others directly attack infected or cancerous cells.<ref name=NIAID>((cite web | title = Understanding the Immune System How It Works | date = September 2003 | work = NIH Publication No. 03-5423 | publisher = National Institute of Allergy and Infectious Diseases National Cancer Institute, U.S. Department of Health and Human Services National Institutes of Health | url = http://www.niaid.nih.gov/publications/immune/the_immune_system.pdf | archive-url= https://web.archive.org/web/20070103005411/http://www.niaid.nih.gov/Publications/immune/the_immune_system.pdf |archive-date=2007-01-03 | url-status = dead ))</ref>]]
CD4+ lymphocytes, also called "helper" T cells, are immune response mediators, and play an important role in establishing and maximizing the capabilities of the acquired immune response.<ref name=Janeway/> These cells have no cytotoxic or phagocytic activity; and cannot kill infected cells or clear pathogens, but, in essence "manage" the immune response, by directing other cells to perform these tasks.((cn|date=September 2022))

Helper T cells express T cell receptors (TCR) that recognize antigen bound to Class II MHC molecules. The activation of a naive helper T-cell causes it to release cytokines, which influences the activity of many cell types, including the APC (Antigen-Presenting Cell) that activated it.  Helper T-cells require a much milder activation stimulus than cytotoxic T cells. Helper T cells can provide extra signals that "help" activate cytotoxic cells.<ref name=Janeway6/>

====Th1 and Th2: helper T cell responses====
Classically, two types of effector CD4<sup>+</sup> T helper cell responses can be induced by a professional APC, designated Th1 and Th2, each designed to eliminate different types of pathogens. The factors that dictate whether an infection triggers a Th1 or Th2 type response are not fully understood, but the response generated does play an important role in the clearance of different pathogens.<ref name=Janeway/>

The Th1 response is characterized by the production of [[Interferon-gamma]], which activates the [[bactericidal]] activities of macrophages, and induces B cells to make [[Opsonin|opsonizing]] (marking for phagocytosis) and complement-fixing antibodies, and leads to ''[[cell-mediated immunity]]''.<ref name=Janeway/> In general, Th1 responses are more effective against [[intracellular]] pathogens (viruses and bacteria that are inside host cells).

The Th2 response is characterized by the release of [[Interleukin 5]], which induces [[eosinophils]] in the clearance of parasites.<ref name="pmid20065995">((cite journal | vauthors = Spencer LA, Weller PF | title = Eosinophils and Th2 immunity: contemporary insights | journal = Immunology and Cell Biology | volume = 88 | issue = 3 | pages = 250–56 | date = 2010 | pmid = 20065995 | pmc = 3589820 | doi = 10.1038/icb.2009.115 ))</ref> Th2 also produce [[Interleukin 4]], which facilitates B cell [[Immunoglobulin class switching|isotype switching]].<ref name=Janeway/> In general, Th2 responses are more effective against [[extracellular]] bacteria, parasites including helminths and [[toxin]]s.<ref name=Janeway/> Like cytotoxic T cells, most of the CD4<sup>+</sup> helper cells die on resolution of infection, with a few remaining as CD4<sup>+</sup> memory cells.

Increasingly, there is strong evidence from mouse and human-based scientific studies of a broader diversity in CD4<sup>+</sup> effector T helper cell subsets.<ref>((cite journal | vauthors = Szabo PA, Levitin HM, Miron M, Snyder ME, Senda T, Yuan J, Cheng YL, Bush EC, Dogra P, Thapa P, Farber DL, Sims PA | display-authors = 6 | title = Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease | journal = Nature Communications | volume = 10 | issue = 1 | pages = 4706 | date = October 2019 | pmid = 31624246 | doi = 10.1038/s41467-019-12464-3 | pmc = 6797728 | bibcode = 2019NatCo..10.4706S | doi-access = free ))</ref><ref>((cite journal | vauthors = Magen A, Nie J, Ciucci T, Tamoutounour S, Zhao Y, Mehta M, Tran B, McGavern DB, Hannenhalli S, Bosselut R | display-authors = 6 | title = + T Cells | language = en | journal = Cell Reports | volume = 29 | issue = 10 | pages = 3019–3032.e6 | date = December 2019 | pmid = 31801070 | doi = 10.1016/j.celrep.2019.10.131 | pmc = 6934378 | doi-access = free ))</ref> [[Regulatory T cells|Regulatory T (Treg) cells]], have been identified as important negative regulators of adaptive immunity as they limit and [[immune tolerance|suppress]] the immune system to control aberrant immune responses to self-antigens; an important mechanism in controlling the development of autoimmune diseases.<ref name=Janeway6/> [[Follicular B helper T cells|Follicular helper T (Tfh) cells]] are another distinct population of effector CD4<sup>+</sup> T cells that develop from naive T cells post-antigen activation. Tfh cells are specialized in helping B cell [[humoral immunity]] as they are uniquely capable of migrating to [[follicular B cells]] in secondary lymphoid organs and provide them positive paracrine signals to enable the generation and recall production of high-quality [[affinity maturation|affinity-matured]] antibodies. Similar to Tregs, Tfh cells also play a role in [[immune tolerance|immunological tolerance]] as an abnormal expansion of Tfh cell numbers can lead to unrestricted autoreactive antibody production causing severe systemic autoimmune disorders.<ref>((cite journal | vauthors = Weinstein JS, Hernandez SG, Craft J | title = T cells that promote B-Cell maturation in systemic autoimmunity | journal = Immunological Reviews | volume = 247 | issue = 1 | pages = 160–71 | date = May 2012 | pmid = 22500839 | pmc = 3334351 | doi = 10.1111/j.1600-065x.2012.01122.x ))</ref>

The relevance of CD4<sup>+</sup> T helper cells is highlighted during an [[HIV]] infection. HIV is able to subvert the immune system by specifically attacking the CD4<sup>+</sup> T cells, precisely the cells that could drive the clearance of the virus, but also the cells that drive immunity against all other pathogens encountered during an organism's lifetime.<ref name=Janeway6/>

===Gamma delta T cells===
((main|Gamma delta T cell))
[[Gamma delta T cell]]s  (γδ T cells) possess an alternative [[T cell receptor]] (TCR) as opposed to CD4+ and CD8+ αβ T cells and share characteristics of helper T cells, cytotoxic T cells and natural killer cells. Like other 'unconventional' T cell subsets bearing invariant TCRs, such as [[CD1d receptor|CD1d]]-restricted [[natural killer T cell]]s, γδ T cells exhibit characteristics that place them at the border between innate and acquired immunity. On one hand, γδ T cells may be considered a component of adaptive immunity in that they rearrange TCR genes via [[V(D)J recombination]], which also produces [[junctional diversity]], and develop a memory phenotype. On the other hand, however, the various subsets may also 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 [[non-peptidic antigen|common molecules]] produced by microbes, and highly restricted intraepithelial Vδ1 T cells respond to stressed epithelial cells.((cn|date=September 2022))

==B lymphocytes and antibody production==
((main|B cell|Humoral immunity))
[[File:B cell activation.svg|thumb|upright=1.15|right|The B lymphocyte activation pathway. B&nbsp;cells function to protect the host by producing antibodies that identify and neutralize foreign objects like bacteria and viruses.<ref name=NIAID/>]]
B Cells are the major cells involved in the creation of [[antibodies]] that circulate in [[blood plasma]] and lymph, known as [[humoral immunity]]. Antibodies (also known as immunoglobulin, Ig), are large Y-shaped proteins used by the immune system to identify and neutralize foreign objects. In mammals, there are five types of antibody: [[IgA]], [[IgD]], [[IgE]], [[Immunoglobulin G|IgG]], and [[IgM]], differing in biological properties; each has evolved to handle different kinds of antigens. Upon activation, B cells produce antibodies, each of which recognize a unique antigen, and neutralizing specific pathogens.<ref name=Janeway/>

Antigen and antibody binding would cause five different protective mechanisms:
* Agglutination: Reduces number of infectious units to be dealt with
* Activation of complement: Cause inflammation and cell lysis
* Opsonization: Coating antigen with antibody enhances phagocytosis
* Antibody-dependent cell-mediated cytotoxicity: Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells
* Neutralization: Blocks adhesion of bacteria and viruses to mucosa

Like the T cell, B cells express a unique B cell receptor (BCR), in this case, a membrane-bound antibody molecule. All the BCR of any one clone of B cells recognizes and binds to only one particular antigen. A critical difference between B cells and T cells is how each cell "sees" an antigen. T cells recognize their cognate antigen in a processed form – as a peptide in the context of an MHC molecule,<ref name=Janeway/> whereas B cells recognize antigens in their native form.<ref name=Janeway/> Once a B cell encounters its cognate (or specific) antigen (and receives additional signals from a [[helper T cell]] (predominately Th2 type)), it further [[cellular differentiation|differentiate]]s into an effector cell, known as a plasma cell.<ref name=Janeway/>

[[Plasma cells]] are short-lived cells (2–3 days) that secrete antibodies. These antibodies bind to antigens, making them easier targets for phagocytes, and trigger the [[complement cascade]].<ref name=Janeway/> About 10% of plasma cells survive to become long-lived antigen-specific [[memory B cell]]s.<ref name=Janeway/> Already primed to produce specific antibodies, these cells can be called upon to respond quickly if the same pathogen re-infects the host, while the host experiences few, if any, symptoms.

==Alternative systems==
=== In jawless vertebrates ===
((main|Adaptive immunity in jawless vertebrates))
Primitive [[agnatha|jawless vertebrates]], such as the [[lamprey]] and [[hagfish]], have an adaptive immune system that shows 3 different cell lineages, each sharing a common origin with B cells, αβ T cells, and innate-like γΔ T cells.<ref>((cite journal |last1=Flajnik |first1=Martin F. |title=A cold-blooded view of adaptive immunity |journal=Nature Reviews Immunology |date=19 March 2018 |volume=18 |issue=7 |pages=438–53 |doi=10.1038/s41577-018-0003-9|pmid=29556016 |pmc=6084782 ))</ref><ref>((Cite journal|last=Kasamatsu|first=Jun|date=January 2013|title=Evolution of innate and adaptive immune systems in jawless vertebrates|journal=Microbiology and Immunology|language=en|volume=57|issue=1|pages=1–12|doi=10.1111/j.1348-0421.2012.00500.x|pmid=22924515|issn=0385-5600|doi-access=free))</ref> Instead of the classical [[antibody|antibodies]] and [[T cell receptor]]s, these animals possess a large array of molecules called [[variable lymphocyte receptor]]s (VLRs for short) that, like the antigen receptors of jawed vertebrates, are produced from only a small number (one or two) of [[gene]]s. These molecules are believed to bind pathogenic [[antigen]]s in a similar way to antibodies, and with the same degree of specificity.<ref>((cite journal | vauthors = Alder MN, Rogozin IB, Iyer LM, Glazko GV, Cooper MD, Pancer Z | title = Diversity and function of adaptive immune receptors in a jawless vertebrate | journal = Science | volume = 310 | issue = 5756 | pages = 1970–73 | date = December 2005 | pmid = 16373579 | doi = 10.1126/science.1119420 | bibcode = 2005Sci...310.1970A | doi-access = free ))</ref>

=== In insects ===
For a long time it was thought that [[insect]]s and other [[invertebrate]]s possess only [[innate immune system]]. However, in recent years some of the basic hallmarks of adaptive immunity have been discovered in insects. Those traits are [[immune memory]] and specificity. Although the hallmarks are present the mechanisms are different from those in [[vertebrate]]s.

Immune memory in insects was discovered through the phenomenon of priming. When insects are exposed to non-lethal dose or heat killed [[bacteria]] they are able to develop a memory of that infection that allows them to withstand otherwise lethal dose of the same bacteria they were exposed to before.<ref>((cite journal | vauthors = Mikonranta L, Mappes J, Kaukoniitty M, Freitak D | title = Insect immunity: oral exposure to a bacterial pathogen elicits free radical response and protects from a recurring infection | journal = Frontiers in Zoology | volume = 11 | issue = 1 | pages = 23 | date = March 2014 | pmid = 24602309 | pmc = 3975449 | doi = 10.1186/1742-9994-11-23 | doi-access = free ))</ref><ref>((cite journal | vauthors = Sadd BM, Schmid-Hempel P | s2cid = 14436004 | title = Insect immunity shows specificity in protection upon secondary pathogen exposure | language = en | journal = Current Biology | volume = 16 | issue = 12 | pages = 1206–10 | date = June 2006 | pmid = 16782011 | doi = 10.1016/j.cub.2006.04.047 | doi-access = free | bibcode = 2006CBio...16.1206S ))</ref> Unlike in vertebrates, insects do not possess cells specific for adaptive immunity. Instead those mechanisms are mediated by [[Hemocyte (invertebrate immune system cell)|hemocytes]]. Hemocytes function similarly to phagocytes and after priming they are able to more effectively recognize and engulf the pathogen.<ref>((cite journal | vauthors = Pham LN, Dionne MS, Shirasu-Hiza M, Schneider DS | title = A specific primed immune response in Drosophila is dependent on phagocytes | journal = PLOS Pathogens | volume = 3 | issue = 3 | pages = e26 | date = March 2007 | pmid = 17352533 | pmc = 1817657 | doi = 10.1371/journal.ppat.0030026 | doi-access = free ))</ref> It was also shown that it is possible to transfer the memory into offspring. For example, in [[Honey bee|honeybees]] if the queen is infected with bacteria then the newly born workers have enhanced abilities in fighting with the same bacteria.<ref name="pmid24789904">((cite journal | vauthors = Hernández López J, Schuehly W, Crailsheim K, Riessberger-Gallé U | title = Trans-generational immune priming in honeybees | journal = Proceedings. Biological Sciences | volume = 281 | issue = 1785 | pages = 20140454 | date = June 2014 | pmid = 24789904 | pmc = 4024302 | doi = 10.1098/rspb.2014.0454 ))</ref> Other experimental model based on [[red flour beetle]] also showed pathogen specific primed memory transfer into offspring from both mothers and fathers.<ref>((cite journal | vauthors = Roth O, Joop G, Eggert H, Hilbert J, Daniel J, Schmid-Hempel P, Kurtz J | title = Paternally derived immune priming for offspring in the red flour beetle, Tribolium castaneum | journal = The Journal of Animal Ecology | volume = 79 | issue = 2 | pages = 403–13 | date = March 2010 | pmid = 19840170 | doi = 10.1111/j.1365-2656.2009.01617.x | doi-access = free | bibcode = 2010JAnEc..79..403R ))</ref>

Most commonly accepted theory of the specificity is based on ''[[DSCAM|Dscam]]'' gene. ''Dscam'' gene also known as Down syndrome cell adhesive molecule is a gene that contains 3 variable [[Immunoglobulin domain|Ig domains]]. Those domains can be alternatively spliced reaching high numbers of variations.<ref name=":0">((cite journal | vauthors = Dong Y, Taylor HE, Dimopoulos G | title = AgDscam, a hypervariable immunoglobulin domain-containing receptor of the Anopheles gambiae innate immune system | journal = PLOS Biology | volume = 4 | issue = 7 | pages = e229 | date = July 2006 | pmid = 16774454 | pmc = 1479700 | doi = 10.1371/journal.pbio.0040229 | doi-access = free ))</ref> It was shown that after exposure to different pathogens there are different splice forms of dscam produced. After the animals with different splice forms are exposed to the same pathogen only the individuals with the splice form specific for that pathogen survive.<ref name=":0" />

Other mechanisms supporting the specificity of insect immunity is [[RNA interference]] (RNAi). RNAi is a form of antiviral immunity with high specificity.<ref>((cite journal | vauthors = Meki IK, Kariithi HM, Parker AG, Vreysen MJ, Ros VI, Vlak JM, van Oers MM, Abd-Alla AM | title = RNA interference-based antiviral immune response against the salivary gland hypertrophy virus in Glossina pallidipes | journal = BMC Microbiology | volume = 18 | issue = Suppl 1 | pages = 170 | date = November 2018 | pmid = 30470195 | pmc = 6251114 | doi = 10.1186/s12866-018-1298-1 | doi-access = free ))</ref> It has several different pathways that all end with the virus being unable to replicate. One of the pathways is [[Small interfering RNA|siRNA]] in which long double stranded RNA is cut into pieces that serve as templates for protein complex Ago2-RISC that finds and degrades complementary RNA of the virus. [[MicroRNA|MiRNA]] pathway in cytoplasm binds to Ago1-RISC complex and functions as a template for viral RNA degradation. Last one is [[Piwi-interacting RNA|piRNA]] where small RNA binds to the Piwi protein family and controls [[Transposons|transposones]] and other mobile elements.<ref>((cite journal | vauthors = Rubio M, Maestro JL, Piulachs MD, Belles X | title = Conserved association of Argonaute 1 and 2 proteins with miRNA and siRNA pathways throughout insect evolution, from cockroaches to flies | journal = Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanisms| volume = 1861 | issue = 6 | pages = 554–60 | date = June 2018 | pmid = 29656113 | doi = 10.1016/j.bbagrm.2018.04.001 | hdl = 10261/168051 | s2cid = 4890483 | hdl-access = free ))</ref> Despite the research the exact mechanisms responsible for immune priming and specificity in insects are not well described.

==Immunological memory==
((further|Immunity (medical)))
When B cells and T cells are activated some become [[memory B cell]]s and some [[memory T cell]]s. Throughout the lifetime of an animal these memory cells form a database of effective B and T lymphocytes. Upon interaction with a previously encountered antigen, the appropriate memory cells are selected and activated. In this manner, the second and subsequent exposures to an antigen produce a stronger and faster immune response. This is "adaptive" in the sense that the body's immune system prepares itself for future challenges, but is "maladaptive" of course if the receptors are autoimmune. Immunological memory can be in the form of either ''passive'' short-term memory or ''active'' long-term memory.((cn|date=November 2023))

===Passive memory===
Passive memory is usually short-term, lasting between a few days and several months. Newborn [[infant]]s have had no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. ''[[Uterus|In utero]]'', [[maternal]] IgG is transported directly across the [[placenta]], so that, at birth, human babies have high levels of antibodies, with the same range of antigen specificities as their mother.<ref name=Janeway/> [[Breast milk]] contains antibodies (mainly IgA) that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its own antibodies.<ref name=Janeway/>

This is [[passive immunization|passive immunity]] because the fetus does not actually make any memory cells or antibodies: It only borrows them. Short-term passive immunity can also be transferred artificially from one individual to another via antibody-rich [[blood plasma|serum]].((cn|date=November 2023))

===Active memory===
In general, active immunity is long-term and can be acquired by infection followed by B cell and T cell activation, or artificially acquired by vaccines, in a process called immunization.

====Immunization====
Historically, infectious disease has been the leading cause of death in the human population. Over the last century, two important factors have been developed to combat their spread: [[sanitation]] and [[immunization]].<ref name=Janeway6/> Immunization (commonly referred to as [[vaccination]]) is the deliberate induction of an immune response, and represents the single most effective manipulation of the immune system that scientists have developed.<ref name=Janeway6/> Immunizations are successful because they utilize the immune system's natural specificity as well as its inducibility.((cn|date=November 2023))

The principle behind immunization is to introduce an antigen, derived from a disease-causing organism, that stimulates the immune system to develop protective immunity against that organism, but that does not itself cause the pathogenic effects of that organism. An [[antigen]] (short for ''anti''body ''gen''erator), is defined as any substance that binds to a specific antibody and elicits an adaptive immune response.<ref name=Alberts/>

Most viral [[vaccine]]s are based on live [[Attenuated vaccine|attenuated]] viruses, whereas many bacterial vaccines are based on [[acellular]] components of microorganisms, including harmless [[toxin]] components.<ref name=Alberts/> Many antigens derived from acellular vaccines do not strongly induce an adaptive response, and most bacterial vaccines require the addition of ''[[Immunologic adjuvant|adjuvant]]s'' that activate the antigen-presenting cells of the [[innate immune system]] to enhance [[immunogenicity]].<ref name=Janeway6/>

==Immunological diversity==
[[File:Antibody chains.svg|thumb|right|An antibody is made up of two heavy chains and two light chains. The unique variable region allows an antibody to recognize its matching antigen.<ref name=NIAID/>]]
Most large molecules, including virtually all [[protein]]s and many [[polysaccharide]]s, can serve as antigens.<ref name=Janeway/> The parts of an antigen that interact with an antibody molecule or a lymphocyte receptor, are called [[epitope]]s, or antigenic determinants. Most antigens contain a variety of epitopes and can stimulate the production of antibodies, specific T cell responses, or both.<ref name=Janeway/>   A very small proportion (less than 0.01%) of the total lymphocytes are able to bind to a particular antigen, which suggests that only a few cells respond to each antigen.<ref name=Janeway6/>

For the acquired response to "remember" and eliminate a large number of pathogens the immune system must be able to distinguish between many different antigens,<ref name=Alberts/> and the receptors that recognize antigens must be produced in a huge variety of configurations, in essence one receptor (at least) for each different pathogen that might ever be encountered. Even in the absence of antigen stimulation, a human can produce more than 1 trillion different antibody molecules.<ref name=Janeway6/> Millions of genes would be required to store the genetic information that produces these receptors, but, the entire human genome contains fewer than 25,000 [[gene]]s.<ref name="IHSGC2004">((cite journal | author = International Human Genome Sequencing Consortium | title = Finishing the euchromatic sequence of the human genome | journal = Nature | volume = 431 | issue = 7011 | pages = 931–45 | date = October 2004 | pmid = 15496913 | doi = 10.1038/nature03001 | bibcode = 2004Natur.431..931H | doi-access = free ))</ref>

Myriad receptors are produced through a process known as [[clonal selection]].<ref name=Alberts/><ref name=Janeway/>  According to the clonal selection theory, at birth, an animal randomly generates a vast diversity of lymphocytes (each bearing a unique antigen receptor) from information encoded in a small family of genes. To generate each unique antigen receptor, these genes have undergone a process called [[V(D)J recombination]], or ''combinatorial diversification'', in which one gene segment recombines with other gene segments to form a single unique gene. This assembly process generates the enormous diversity of receptors and antibodies, before the body ever encounters antigens, and enables the immune system to respond to an almost unlimited diversity of antigens.<ref name=Janeway/> Throughout an animal's lifetime, lymphocytes that can react against the antigens an animal actually encounters are selected for action—directed against anything that expresses that antigen.((cn|date=November 2023))

The innate and acquired portions of the immune system work together, not in spite of each other. The acquired arm, B, and T cells could not function without the innate system input. T cells are useless without antigen-presenting cells to activate them, and B cells are disabled without T cell help. On the other hand, the innate system would likely be overrun with pathogens without the specialized action of the adaptive immune response.

==Acquired immunity during pregnancy==
The cornerstone of the immune system is the recognition of "self" versus "non-self". Therefore, the mechanisms that protect the human [[fetus]] (which is considered "non-self") from attack by the immune system, are particularly interesting. Although no comprehensive explanation has emerged to explain this mysterious, and often repeated, lack of rejection, two classical reasons may explain how the fetus is tolerated. The first is that the fetus occupies a portion of the body protected by a non-immunological barrier, the [[uterus]], which the immune system does not routinely patrol.<ref name=Janeway/> The second is that the fetus itself may promote local immunosuppression in the mother, perhaps by a process of active nutrient depletion.<ref name=Janeway/> A more modern explanation for this induction of tolerance is that specific glycoproteins expressed in the uterus during [[pregnancy]] suppress the uterine immune response (see [[eu-FEDS]]).((cn|date=November 2023))

During pregnancy in [[viviparity|viviparous]] mammals (all mammals except [[Monotreme]]s), [[endogenous retroviruses]] (ERVs) are activated and produced in high quantities during the implantation of the embryo. They are currently known to possess immunosuppressive properties, suggesting a role in protecting the embryo from its mother's immune system. Also, [[viral fusion proteins]] cause the formation of the placental [[syncytium]]<ref>((cite journal | vauthors = Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S, Keith JC, McCoy JM | s2cid = 4367889 | title = Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis | journal = Nature | volume = 403 | issue = 6771 | pages = 785–89 | date = February 2000 | pmid = 10693809 | doi = 10.1038/35001608 | bibcode = 2000Natur.403..785M ))
</ref> to limit exchange of migratory cells between the developing embryo and the body of the mother (something an [[epithelium]] cannot do sufficiently, as certain blood cells specialize to insert themselves between adjacent epithelial cells). The immunodepressive action was the initial normal behavior of the virus, similar to HIV. The fusion proteins were a way to spread the infection to other cells by simply merging them with the infected one (HIV does this too). It is believed that the ancestors of modern viviparous mammals evolved after an infection by this virus, enabling the fetus to survive the immune system of the mother.<ref>((cite web
|url=http://www.dbc.uci.edu/~faculty/villarreal/new1/erv-placental.html
|archive-url=https://archive.today/20070715005236/http://www.dbc.uci.edu/~faculty/villarreal/new1/erv-placental.html
|url-status=dead
|archive-date=2007-07-15
|title=The Viruses That Make Us: A Role For Endogenous Retrovirus In The Evolution Of Placental Species
| first = Luis P. | last = Villarreal | name-list-style = vanc
|publisher=University of California, Irvine (lecture notes)
|access-date=2008-02-03 ))</ref>

The [[human genome project]] found several thousand [[endogenous retrovirus|ERV]]s classified into 24 families.<ref>((cite journal | url = http://newsarchive.asm.org/oct01/feature1.asp | title = Persisting Viruses Could Play Role in Driving Host Evolution | first = Luis P. | last = Villarreal | name-list-style = vanc | journal = ASM News | date = Oct 2001 | url-status = dead | archive-url = https://web.archive.org/web/20090508113235/http://newsarchive.asm.org/oct01/feature1.asp | archive-date = 2009-05-08 ))</ref>

==Immune network theory==
((Main|Immune network theory))
A theoretical framework explaining the workings of the acquired immune system is provided by [[immune network theory]], based on interactions between [[idiotypes]] (unique molecular features of one clonotype, i.e. the unique set of [[antigenic determinants]] of the variable portion of an antibody) and 'anti-idiotypes' (antigen receptors that react with the idiotype as if it were a foreign antigen). This theory, which builds on the existing [[clonal selection]] hypothesis and since 1974 has been developed mainly by [[Niels Jerne]] and [[Geoffrey W. Hoffmann]], is seen as being relevant to the understanding of the [[Pathophysiology of HIV/AIDS|HIV pathogenesis]] and the search for an [[HIV vaccine]].

=== Stimulation of adaptive immunity ===
One of the most interesting developments in biomedical science during the past few decades has been elucidation of mechanisms mediating innate immunity.  One set of innate immune mechanisms is humoral, such as [[complement system|complement activation]].  Another set comprises pattern recognition receptors such as [[toll-like receptor]]s, which induce the production of interferons and other cytokines increasing resistance of cells such as monocytes to infections.<ref name=Uematsu/> Cytokines produced during innate immune responses are among the activators of adaptive immune responses.<ref name=Uematsu/> Antibodies exert additive or synergistic effects with mechanisms of innate immunity. Unstable HbS clusters Band-3, a major integral red cell protein;<ref name=Kuross>((cite journal | vauthors = Kuross SA, Rank BH, Hebbel RP | title = Excess heme in sickle erythrocyte inside-out membranes: possible role in thiol oxidation | journal = Blood | volume = 71 | issue = 4 | pages = 876–82 | date = April 1988 | pmid = 3355895 | url = http://bloodjournal.hematologylibrary.org/cgi/reprint/71/4/876.pdf | doi = 10.1182/blood.V71.4.876.876 | doi-access = free ))</ref> antibodies recognize these clusters and accelerate their removal by phagocytic cells. Clustered Band 3 proteins with attached antibodies activate complement, and complement C3 fragments are opsonins recognized by the CR1 complement receptor on phagocytic cells.<ref>((cite journal | vauthors = Arese P, Turrini F, Schwarzer E | title = Band 3/complement-mediated recognition and removal of normally senescent and pathological human erythrocytes | journal = Cellular Physiology and Biochemistry | volume = 16 | issue = 4–6 | pages = 133–46 | year = 2005 | pmid = 16301814 | doi = 10.1159/000089839 | doi-access = free ))</ref>

A population study has shown that the protective effect of the sickle-cell trait against falciparum malaria involves the augmentation of acquired as well as innate immune responses to the malaria parasite, illustrating the expected transition from innate to acquired immunity.<ref name=Williams>((cite journal | vauthors = Williams TN, Mwangi TW, Roberts DJ, Alexander ND, Weatherall DJ, Wambua S, Kortok M, Snow RW, Marsh K | title = An immune basis for malaria protection by the sickle cell trait | journal = PLOS Medicine | volume = 2 | issue = 5 | pages = e128 | date = May 2005 | pmid = 15916466 | pmc = 1140945 | doi = 10.1371/journal.pmed.0020128 | doi-access = free ))</ref>

Repeated malaria infections strengthen acquired immunity and broaden its effects against parasites expressing different surface [[antigen]]s.  By school age most children have developed efficacious adaptive immunity against malaria. These observations raise questions about mechanisms that favor the survival of most children in Africa while allowing some to develop potentially lethal infections.

In malaria, as in other infections,<ref name=Uematsu >((cite journal | vauthors = Uematsu S, Akira S | title = Toll-like receptors and Type I interferons | journal = The Journal of Biological Chemistry | volume = 282 | issue = 21 | pages = 15319–23 | date = May 2007 | pmid = 17395581 | doi = 10.1074/jbc.R700009200 | doi-access = free ))</ref> innate immune responses lead into, and stimulate, adaptive immune responses. The genetic control of innate and acquired immunity is now a large and flourishing discipline.

Humoral and cell-mediated immune responses limit malaria parasite multiplication, and many cytokines contribute to the pathogenesis of malaria as well as to the resolution of infections.<ref>((cite journal | vauthors = Schofield L, Grau GE | s2cid = 19594405 | title = Immunological processes in malaria pathogenesis | journal = Nature Reviews. Immunology | volume = 5 | issue = 9 | pages = 722–35 | date = September 2005 | pmid = 16138104 | doi = 10.1038/nri1686 | doi-access = free ))</ref>

==Evolution==
The acquired immune system, which has been best-studied in mammals, originated in jawed fish approximately 500 million years ago.  Most of the molecules, cells, tissues, and associated mechanisms of this system of defense are found in [[cartilaginous fishes]].<ref name="pmid19997068">((cite journal | vauthors = Flajnik MF, Kasahara M | title = Origin and evolution of the adaptive immune system: genetic events and selective pressures | journal = Nature Reviews. Genetics | volume = 11 | issue = 1 | pages = 47–59 | date = January 2010 | pmid = 19997068 | pmc = 3805090 | doi = 10.1038/nrg2703 ))</ref> [[Lymphocyte]] receptors, Ig and TCR, are found in all jawed vertebrates.  The most ancient Ig class, IgM, is membrane-bound and then secreted upon stimulation of cartilaginous fish B cells.  Another isotype, shark IgW, is related to mammalian IgD.  TCRs, both α/β and γ/δ, are found in all animals from [[gnathostomes]] to mammals.  The organization of gene segments that undergo [[V(D)J recombination|gene rearrangement]] differs in cartilaginous fishes, which have a cluster form as compared to the translocon form in bony fish to mammals. Like TCR and Ig, the MHC is found only in jawed vertebrates.  Genes involved in [[antigen processing]] and [[antigen presentation|presentation]], as well as the [[MHC class I|class I]] and [[MHC class II|class II]] genes, are closely linked within the MHC of almost all studied species.((cn|date=November 2023))

Lymphoid cells can be identified in some pre-vertebrate [[deuterostomes]] (i.e., sea urchins).<ref name="pmid17027739">((cite journal | vauthors = Hibino T, Loza-Coll M, Messier C, Majeske AJ, Cohen AH, Terwilliger DP, Buckley KM, Brockton V, Nair SV, Berney K, Fugmann SD, Anderson MK, Pancer Z, Cameron RA, Smith LC, Rast JP | title = The immune gene repertoire encoded in the purple sea urchin genome | journal = Developmental Biology | volume = 300 | issue = 1 | pages = 349–65 | date = December 2006 | pmid = 17027739 | doi = 10.1016/j.ydbio.2006.08.065 | url = https://authors.library.caltech.edu/35195/2/mmc1.pdf | doi-access = free ))</ref> These bind antigen with [[pattern recognition receptor]]s (PRRs) of the [[innate immune system]].  In [[jawless fishes]], two subsets of [[lymphocytes]] use variable lymphocyte receptors (VLRs) for antigen binding.<ref name="pmid15241406">((cite journal | vauthors = Pancer Z, Amemiya CT, Ehrhardt GR, Ceitlin J, Gartland GL, Cooper MD | s2cid = 876413 | title = Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey | journal = Nature | volume = 430 | issue = 6996 | pages = 174–80 | date = July 2004 | pmid = 15241406 | doi = 10.1038/nature02740 | bibcode = 2004Natur.430..174P | url = https://deepblue.lib.umich.edu/bitstream/2027.42/62870/1/nature02740.pdf | hdl = 2027.42/62870 | hdl-access = free ))</ref> Diversity is generated by a [[cytosine deaminase]]-mediated rearrangement of [[leucine-rich repeat|LRR]]-based DNA segments.<ref name="pmid17468760">((cite journal | vauthors = Rogozin IB, Iyer LM, Liang L, Glazko GV, Liston VG, Pavlov YI, Aravind L, Pancer Z | s2cid = 3658963 | title = Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase | journal = Nature Immunology | volume = 8 | issue = 6 | pages = 647–56 | date = June 2007 | pmid = 17468760 | doi = 10.1038/ni1463 ))</ref> There is no evidence for the [[recombination-activating gene]]s (RAGs) that rearrange Ig and TCR gene segments in jawed vertebrates.

The evolution of the AIS, based on Ig, TCR, and MHC molecules, is thought to have arisen from two major evolutionary events: the transfer of the [[recombination activating gene|RAG]] [[transposon]] (possibly of viral origin) and two [[whole genome duplication]]s.<ref name="pmid19997068" />   Though the molecules of the AIS are well-conserved, they are also rapidly evolving.  Yet, a comparative approach finds that many features are quite uniform across taxa.  All the major features of the AIS arose early and quickly.  Jawless fishes have a [[Adaptive immunity in jawless fish|different AIS]] that relies on gene rearrangement to generate diverse immune receptors with a functional dichotomy that parallels Ig and TCR molecules.<ref>((cite journal | vauthors = Boehm T | s2cid = 25989912 | title = Design principles of adaptive immune systems | journal = Nature Reviews. Immunology | volume = 11 | issue = 5 | pages = 307–17 | date = May 2011 | pmid = 21475308 | doi = 10.1038/nri2944 ))</ref> The [[innate immune system]], which has an important role in AIS activation, is the most important defense system of [[invertebrate]]s and [[plant]]s.

==Types of acquired immunity==
Immunity can be acquired either actively or passively. Immunity is acquired actively when a person is exposed to foreign substances and the immune system responds. Passive immunity is when antibodies are transferred from one host to another. Both actively acquired and passively acquired immunity can be obtained by natural or artificial means.
* ''Naturally Acquired Active Immunity'' – when a person is naturally exposed to antigens, becomes ill, then recovers.
* ''Naturally Acquired Passive Immunity'' – involves a natural transfer of antibodies from a mother to her infant. The antibodies cross the woman's placenta to the fetus. Antibodies can also be transferred through breast milk with the secretions of colostrum.
* ''Artificially Acquired Active Immunity'' – is done by vaccination (introducing dead or weakened antigen to the host's cell).
* ''Artificially Acquired Passive Immunity'' – This involves the introduction of antibodies rather than antigens to the human body. These antibodies are from an animal or person who is already immune to the disease.

{| class="wikitable"
|-Adaptive immunity
! Naturally acquired !! Artificially acquired
|-
| '''Active''' – Antigen enters the body naturally || '''Active''' – Antigens are introduced in vaccines.
|-
| '''Passive''' – Antibodies pass from mother to fetus via placenta or infant via the mother's milk. || '''Passive''' – Preformed antibodies in immune serum are introduced by injection.
|-
|}

== See also ==
((commons category|Adaptive immunity))
((div col|colwidth=18em))
* [[Affinity maturation]]
* [[Allelic exclusion]]
* [[Anergy]]
* [[Immune response]]
* [[Immune tolerance]]
* [[Immunosuppression]]
* [[Original antigenic sin]]
* [[Somatic hypermutation]]
* [[Polyclonal response]]
((div col end))

==Notes and references==
;Notes
((reflist|group= n))

;References
((Reflist|30em))

((immune_system))
((lymphatic system))
((organ systems))

((DEFAULTSORT:Adaptive Immune System))
[[Category:Immune system]]

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Module:Pagetype/disambiguation (view source) (protected)
Module:Pagetype/setindex (view source) (protected)
Module:Pagetype/softredirect (view source) (protected)
Module:SDcat (view source) (protected)
Module:Side box (view source) (template editor protected)
Module:Side box/styles.css (view source) (template editor protected)
Module:String (view source) (protected)
Module:Unsubst (view source) (protected)
Module:WikidataIB (view source) (template editor protected)
Module:WikidataIB/nolinks (view source) (template editor protected)
Module:WikidataIB/titleformats (view source) (template editor protected)
Module:Wikitext Parsing (view source) (protected)
Module:Yesno (view source) (protected)

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