Editing Immune system (section)

== Adaptive immune system ==
{{further|Adaptive immune system}}
[[File:Primary immune response 1.png|thumb|upright=1.5 |alt=diagram showing the processes of activation, cell destruction and digestion, antibody production and proliferation, and response memory |Overview of the processes involved in the primary immune response]]
The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as [[immunological memory]], where each pathogen is "remembered" by a signature antigen.<ref>{{cite journal | vauthors = Pancer Z, Cooper MD | title = The evolution of adaptive immunity | journal = Annual Review of Immunology | volume = 24 | issue = 1 | pages = 497–518 | year = 2006 | pmid = 16551257 | doi = 10.1146/annurev.immunol.24.021605.090542 }}</ref> The adaptive immune response is antigen-specific and requires the recognition of specific "non-self" antigens during a process called [[antigen presentation]]. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.{{sfn | Sompayrac | 2019 | p=38}}

===Recognition of antigen===
The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. [[B cell]]s and T cells are the major types of lymphocytes and are derived from [[hematopoietic stem cell]]s in the [[bone marrow]].{{sfn| Janeway |2005 |p=}} B cells are involved in the [[humoral immunity|humoral immune response]], whereas T cells are involved in [[cell-mediated immunity|cell-mediated immune response]]. Killer T cells only recognize antigens coupled to [[Major histocompatibility complex#MHC class I|Class I MHC]] molecules, while helper T cells and regulatory T cells only recognize antigens coupled to [[Major histocompatibility complex#MHC class II|Class II MHC]] molecules. These two mechanisms of antigen presentation reflect the different roles of the two types of T cell. A third, minor subtype are the [[gamma/delta T cells|γδ T cells]] that recognize intact antigens that are not bound to MHC receptors.<ref name="Holtmeier W, Kabelitz D 2005 151–83">{{cite journal | vauthors = Holtmeier W, Kabelitz D | title = gammadelta T cells link innate and adaptive immune responses | volume = 86 | pages = 151–83 | year = 2005 | pmid = 15976493 | doi = 10.1159/000086659 | isbn = 3-8055-7862-8 | journal = Chemical Immunology and Allergy }}</ref> The double-positive T cells are exposed to a wide variety of [[Self-protein|self-antigens]] in the [[thymus]], in which [[iodine]] is necessary for its thymus development and activity.<ref name="pmid19647627">{{cite journal | vauthors = Venturi S, Venturi M | title = Iodine, thymus, and immunity | journal = Nutrition | volume = 25 | issue = 9 | pages = 977–79 | date = September 2009 | pmid = 19647627 | doi = 10.1016/j.nut.2009.06.002 }}</ref> In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface and recognizes native (unprocessed) antigen without any need for [[antigen processing]]. Such antigens may be large molecules found on the surfaces of pathogens, but can also be small [[hapten]]s (such as penicillin) attached to carrier molecule.{{sfn|Janeway|Travers|Walport|2001|loc= sec. [https://www.ncbi.nlm.nih.gov/books/NBK27112/#A1746 12-10]}} Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture.{{sfn| Janeway |2005 |p=}} When B or T cells encounter their related antigens they multiply and many "clones" of the cells are produced that target the same antigen. This is called [[clonal selection]].{{sfn | Sompayrac | 2019 | pp= 5–6}}

===Antigen presentation to T lymphocytes===
Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a "non-self" target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a "self" receptor called a major histocompatibility complex (MHC) molecule.{{sfn | Sompayrac | 2019 | pp=51–53}}

===Cell mediated immunity===
{{Further|Cell-mediated immunity}}
There are two major subtypes of T cells: the [[cytotoxic T cell|killer T cell]] and the [[T helper cell|helper T cell]]. In addition there are [[regulatory T cells]] which have a role in modulating immune response.{{sfn | Sompayrac | 2019 | pp=7–8}}

==== Killer T cells ====
[[Killer T cells]] are a sub-group of T cells that kill cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional.<ref>{{cite journal | vauthors = Harty JT, Tvinnereim AR, White DW | title = CD8+ T cell effector mechanisms in resistance to infection | journal = Annual Review of Immunology | volume = 18 | issue = 1 | pages = 275–308 | year = 2000 | pmid = 10837060 | doi = 10.1146/annurev.immunol.18.1.275 }}</ref> As with B cells, each type of T cell recognizes a different antigen. Killer T cells are activated when their [[T-cell receptor]] binds to this specific antigen in a complex with the MHC Class I receptor of another cell. Recognition of this MHC:antigen complex is aided by a [[co-receptor]] on the T cell, called [[CD8]]. The T cell then travels throughout the body in search of cells where the MHC I receptors bear this antigen. When an activated T cell contacts such cells, it releases [[cytotoxicity|cytotoxins]], such as [[perforin]], which form pores in the target cell's [[cell membrane|plasma membrane]], allowing [[ion]]s, water and toxins to enter. The entry of another toxin called [[granulysin]] (a protease) induces the target cell to undergo [[apoptosis]].<ref name=Radoja>{{cite journal | vauthors = Radoja S, Frey AB, Vukmanovic S | title = T-cell receptor signaling events triggering granule exocytosis | journal = [[Critical Reviews in Immunology]] | volume = 26 | issue = 3 | pages = 265–90 | year = 2006 | pmid = 16928189 | doi = 10.1615/CritRevImmunol.v26.i3.40 }}</ref> T cell killing of host cells is particularly important in preventing the replication of viruses. T cell activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T cells (see below).<ref name=Radoja />

==== Helper T cells ====
[[File:Activation of T and B cells.png|thumb|right|400px|Activation of macrophage or B cell by T helper cell]]
[[T helper cell|Helper T cells]] regulate both the innate and adaptive immune responses and help determine which immune responses the body makes to a particular pathogen.<ref>{{cite journal | vauthors = Abbas AK, Murphy KM, Sher A | title = Functional diversity of helper T lymphocytes | journal = Nature | volume = 383 | issue = 6603 | pages = 787–93 | date = Oct 1996 | pmid = 8893001 | doi = 10.1038/383787a0 | bibcode = 1996Natur.383..787A | s2cid = 4319699 }}</ref><ref>{{cite book | vauthors = McHeyzer-Williams LJ, Malherbe LP, McHeyzer-Williams MG | title = From Innate Immunity to Immunological Memory | chapter = Helper T cell-regulated B cell immunity | volume = 311 | pages = 59–83 | year = 2006 | pmid = 17048705 | doi = 10.1007/3-540-32636-7_3 | isbn = 978-3-540-32635-9 | series = Current Topics in Microbiology and Immunology }}</ref> These cells have no cytotoxic activity and do not kill infected cells or clear pathogens directly. They instead control the immune response by directing other cells to perform these tasks.{{sfn | Sompayrac | 2019 | p=8}}

Helper T cells express T cell receptors that recognize antigen bound to Class II MHC molecules. The MHC:antigen complex is also recognized by the helper cell's [[CD4]] co-receptor, which recruits molecules inside the T cell (such as [[Lck]]) that are responsible for the T cell's activation. Helper T cells have a weaker association with the MHC:antigen complex than observed for killer T cells, meaning many receptors (around 200–300) on the helper T cell must be bound by an MHC:antigen to activate the helper cell, while killer T cells can be activated by engagement of a single MHC:antigen molecule. Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell.<ref>{{cite journal | vauthors = Kovacs B, Maus MV, Riley JL, Derimanov GS, Koretzky GA, June CH, Finkel TH | title = Human CD8+ T cells do not require the polarization of lipid rafts for activation and proliferation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 23 | pages = 15006–11 | date = Nov 2002 | pmid = 12419850 | pmc = 137535 | doi = 10.1073/pnas.232058599 | bibcode = 2002PNAS...9915006K | doi-access = free }}</ref> The activation of a resting helper T cell causes it to release cytokines that influence the activity of many cell types. Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells.{{sfn|Alberts|Johnson|Lewis|Raff|2002|loc=Chapter. [https://www.ncbi.nlm.nih.gov/books/NBK26827/ "Helper T Cells and Lymphocyte Activation"]}} In addition, helper T cell activation causes an upregulation of molecules expressed on the T cell's surface, such as CD40 ligand (also called [[CD154]]), which provide extra stimulatory signals typically required to activate antibody-producing B cells.<ref>{{cite journal | vauthors = Grewal IS, Flavell RA | title = CD40 and CD154 in cell-mediated immunity | journal = Annual Review of Immunology | volume = 16 | issue = 1 | pages = 111–35 | year = 1998 | pmid = 9597126 | doi = 10.1146/annurev.immunol.16.1.111 }}</ref>
==== Gamma delta T cells ====
[[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 the characteristics of helper T cells, cytotoxic T cells and NK cells. The conditions that produce responses from γδ T cells are not fully understood. Like other 'unconventional' T cell subsets bearing invariant TCRs, such as [[CD1d receptor|CD1d]]-restricted [[natural killer T cell]]s, γδ T cells straddle the border between innate and adaptive immunity.<ref>{{cite journal | vauthors = Girardi M | title = Immunosurveillance and immunoregulation by gammadelta T cells | journal = The Journal of Investigative Dermatology | volume = 126 | issue = 1 | pages = 25–31 | date = Jan 2006 | pmid = 16417214 | doi = 10.1038/sj.jid.5700003 | doi-access = free }}</ref> On one hand, γδ T cells are a component of adaptive immunity as they [[V(D)J recombination|rearrange TCR genes]] to produce receptor diversity and can also develop a memory phenotype. On the other hand, the various subsets are also part of the innate immune system, as restricted TCR or NK receptors may be used as [[pattern recognition receptor]]s. For example, large numbers of human Vγ9/Vδ2 T cells respond within hours to [[non-peptidic antigen|common molecules]] produced by microbes, and highly restricted Vδ1+ T cells in [[epithelium|epithelia]] respond to stressed epithelial cells.<ref name="Holtmeier W, Kabelitz D 2005 151–83" />

===Humoral immune response===
{{further|Humoral immunity}}
[[File:2220 Four Chain Structure of a Generic Antibody-IgG2 Structures.jpg|thumb|upright=1.6 |alt=diagram showing the Y-shaped antibody. The variable region, including the antigen-binding site, is the top part of the two upper light chains. The remainder is the constant region. |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>{{cite web|title=Understanding the Immune System: How it Works |publisher=[[National Institute of Allergy and Infectious Diseases]] (NIAID) |url=https://www.niaid.nih.gov/publications/immune/the_immune_system.pdf |access-date=1 January 2007 |url-status=dead |archive-url=https://web.archive.org/web/20070103005411/http://www.niaid.nih.gov/Publications/immune/the_immune_system.pdf |archive-date=3 January 2007 }}</ref>]]
A [[B cell]] identifies pathogens when antibodies on its surface bind to a specific foreign antigen.<ref name=Sproul>{{cite journal | vauthors = Sproul TW, Cheng PC, Dykstra ML, Pierce SK | s2cid = 6550357 | title = A role for MHC class II antigen processing in B cell development | journal = International Reviews of Immunology | volume = 19 | issue = 2–3 | pages = 139–55 | year = 2000 | pmid = 10763706 | doi = 10.3109/08830180009088502 }}</ref> This antigen/antibody complex is taken up by the B cell and processed by [[proteolysis]] into [[peptide]]s. The B cell then displays these antigenic peptides on its surface MHC class II molecules. This combination of MHC and antigen attracts a matching helper T cell, which releases [[lymphokine]]s and activates the B cell.<ref>{{cite journal | vauthors = Parker DC | title = T cell-dependent B cell activation | journal = Annual Review of Immunology | volume = 11 | pages = 331–60 | date = 1993 | pmid = 8476565 | doi = 10.1146/annurev.iy.11.040193.001555 }}</ref> As the activated B cell then begins to [[cell division|divide]], its offspring ([[plasma cells]]) [[secretion|secrete]] millions of copies of the antibody that recognizes this antigen. These antibodies circulate in [[blood plasma]] and [[lymphatic system|lymph]], bind to pathogens expressing the antigen and mark them for destruction by [[Complement system|complement activation]] or for uptake and destruction by [[phagocyte]]s. Antibodies can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that viruses and bacteria use to infect cells.{{sfn| Murphy |Weaver |2016 |loc= Chapter 10: The Humoral Immune Response}}

Newborn infants have no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. During pregnancy, a particular type of antibody, called [[Immunoglobulin G|IgG]], is transported from mother to baby directly through the [[placenta]], so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother.<ref>{{cite journal | vauthors = Saji F, Samejima Y, Kamiura S, Koyama M | title = Dynamics of immunoglobulins at the feto-maternal interface | journal = Reviews of Reproduction | volume = 4 | issue = 2 | pages = 81–89 | date = May 1999 | pmid = 10357095 | doi = 10.1530/ror.0.0040081 | s2cid = 31099552 | url = http://pdfs.semanticscholar.org/ef69/261377c9d417b646679b850fc88a19128579.pdf | archive-url = https://web.archive.org/web/20210130212930/http://pdfs.semanticscholar.org/ef69/261377c9d417b646679b850fc88a19128579.pdf | url-status = dead | archive-date = 2021-01-30 }}</ref> Breast milk or [[colostrum]] also contains antibodies that are transferred to the gut of the infant and protect against bacterial infections until the newborn can synthesize its own antibodies.<ref>{{cite journal | vauthors = Van de Perre P | title = Transfer of antibody via mother's milk | journal = Vaccine | volume = 21 | issue = 24 | pages = 3374–76 | date = Jul 2003 | pmid = 12850343 | doi = 10.1016/S0264-410X(03)00336-0 }}</ref> This is [[passive immunization|passive immunity]] because the [[fetus]] does not actually make any memory cells or antibodies—it only borrows them. This passive immunity is usually short-term, lasting from a few days up to several months. In medicine, protective passive immunity can also be [[intravenous immunoglobulin|transferred artificially]] from one individual to another.<ref name= Keller>{{cite journal | vauthors = Keller MA, Stiehm ER | title = Passive immunity in prevention and treatment of infectious diseases | journal = Clinical Microbiology Reviews | volume = 13 | issue = 4 | pages = 602–14 | date = Oct 2000 | pmid = 11023960 | pmc = 88952 | doi = 10.1128/CMR.13.4.602-614.2000 }}</ref>

=== Immunological memory ===
{{further|Immunity (medical)}}
When B cells and T cells are activated and begin to replicate, some of their offspring become long-lived memory cells. Throughout the lifetime of an animal, these memory cells remember each specific pathogen encountered and can mount a strong response if the pathogen is detected again. T-cells recognize pathogens by small protein-based infection signals, called antigens, that bind directly to T-cell surface receptors.<ref>Sauls RS, McCausland C, Taylor BN. Histology, T-Cell Lymphocyte. In: StatPearls. StatPearls Publishing; 2023. Accessed November 15, 2023. http://www.ncbi.nlm.nih.gov/books/NBK535433/</ref> B-cells use the protein, immunoglobulin, to recognize pathogens by their antigens.<ref>	Althwaiqeb SA, Bordoni B. Histology, B Cell Lymphocyte. In: StatPearls. StatPearls Publishing; 2023. Accessed November 15, 2023. http://www.ncbi.nlm.nih.gov/books/NBK560905/</ref> This is "adaptive" because it occurs during the lifetime of an individual as an adaptation to infection with that pathogen and prepares the immune system for future challenges. Immunological memory can be in the form of either passive short-term memory or active long-term memory.{{sfn | Sompayrac | 2019 | p=98}}