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{{short description|Model of the immune system response to infection}}
{{About||the use of clonal selection in general horticulture|Clonal (plant)|the use of clonal selection in viticulture|Propagation of grapevines}}
{{About||the use of clonal selection in general horticulture|Clonal (plant)|the use of clonal selection in viticulture|Propagation of grapevines}}
{{Use dmy dates|date=February 2024}}
[[Image:Clonal selection.svg|thumb|200px|
[[Image:Clonal selection.svg|thumb|200px|'''Clonal selection theory''' of [[lymphocyte]]s: <br>
'''Clonal selection Theory''' of [[lymphocyte]]s: 1) A [[hematopoietic stem cell]] undergoes differentiation and genetic rearrangement to produce 2) immature lymphocytes with many different antigen receptors. Those that bind to 3) antigens from the body's own tissues are destroyed, while the rest mature into 4) inactive lymphocytes. Most of these will never encounter a matching 5) foreign antigen, but those that do are activated and produce 6) many clones of themselves.]]
1) A [[hematopoietic stem cell]] undergoes differentiation and genetic rearrangement to produce <br>
2) immature lymphocytes with many different antigen receptors. Those that bind to <br>
3) antigens from the body's own tissues are destroyed, while the rest mature into <br>
4) inactive lymphocytes. Most of these never encounter a matching <br>
5) foreign antigen, but those that do are activated and produce <br>
6) many clones of themselves.]]


'''Clonal selection theory''' is a [[scientific theory]] in [[immunology]] that explains the functions of cells ([[lymphocytes]]) of the [[immune system]] in response to specific [[antigens]] invading the body. The concept was introduced by the Australian doctor [[Frank Macfarlane Burnet]] in 1957, in an attempt to explain the formation of a diversity of antibodies during initiation of the [[immune response]].<ref>{{cite journal|last=Burnet|first=FM|title=A modification of Jerne's theory of antibody production using the concept of clonal selection.|journal=CA: A Cancer Journal for Clinicians|year=1976|volume=26|issue=2|pages=119–21|pmid=816431|doi=10.3322/canjclin.26.2.119}}</ref><ref>{{cite journal|last=Cohn|first=Melvin|author2=Av Mitchison, N. |author3=Paul, William E. |author4=Silverstein, Arthur M. |author5=Talmage, David W. |author6=Weigert, Martin |title=Reflections on the clonal-selection theory|journal=Nature Reviews Immunology|year=2007|volume=7|issue=10|pages=823–830|doi=10.1038/nri2177|pmid=17893695}}</ref> The theory has become a widely accepted model for how the [[immune system]] responds to [[infection]] and how certain types of [[B cells|B]] and [[T lymphocytes]] are selected for destruction of specific [[antigens]].<ref name="Rajewsky1996">{{cite journal|last1=Rajewsky|first1=Klaus|title=Clonal selection and learning in the antibody system|journal=Nature|volume=381|issue=6585|year=1996|pages=751–758|issn=0028-0836|doi=10.1038/381751a0}}</ref>
In [[immunology]], '''clonal selection theory''' explains the functions of cells of the [[immune system]] ([[lymphocytes]]) in response to specific [[antigens]] invading the body. The concept was introduced by Australian doctor [[Frank Macfarlane Burnet]] in 1957, in an attempt to explain the great diversity of [[antibodies]] formed during initiation of the [[immune response]].<ref>{{cite journal|last=Burnet|first=FM|title=A modification of Jerne's theory of antibody production using the concept of clonal selection.|journal=CA: A Cancer Journal for Clinicians|year=1976|volume=26|issue=2|pages=119–21|pmid=816431|doi=10.3322/canjclin.26.2.119|s2cid=40609269|doi-access=free}}</ref><ref>{{cite journal|last=Cohn|first=Melvin|author2=Av Mitchison, N. |author3=Paul, William E. |author4=Silverstein, Arthur M. |author5=Talmage, David W. |author6=Weigert, Martin |title=Reflections on the clonal-selection theory|journal=Nature Reviews Immunology|year=2007|volume=7|issue=10|pages=823–830|doi=10.1038/nri2177|pmid=17893695|s2cid=24741671}}</ref> The theory has become the widely accepted model for how the human [[immune system]] responds to infection and how certain types of [[B cells|B]] and [[T lymphocytes]] are selected for destruction of specific [[antigens]].<ref name="Rajewsky1996">{{cite journal|last1=Rajewsky|first1=Klaus|title=Clonal selection and learning in the antibody system|journal=Nature|volume=381|issue=6585|year=1996|pages=751–758|issn=0028-0836|doi=10.1038/381751a0|pmid=8657279|bibcode=1996Natur.381..751R |s2cid=4279640}}</ref>


The theory states that in a pre-existing group of lymphocytes (specifically B cells), a specific antigen only activates (i.e. selection) its counter-specific cell so that particular cell is induced to multiply (producing its [[Clone (genetics)|clones]]) for antibody production. This activation occurs in secondary lymphoid organs such as the [[spleen]] and the [[Lymph Node|lymph node]]s.<ref>{{Cite book|title = Janeway's Immunobiology 8th Edition|last = Murphy|first = Kenneth|publisher = Garland Science|year = 2012|isbn = 9780815342434|location = New York, NY|pages = }}</ref> In short the theory is an explanation of the mechanism for the generation of diversity of antibody specificity.<ref name="Jordan 2007 72–79">{{cite journal|last=Jordan|first=Margaret A|author2=Baxter, Alan G|title=Quantitative and qualitative approaches to GOD: the first 10 years of the clonal selection theory|journal=Immunology and Cell Biology|year=2007|volume=86|issue=1|pages=72–79|doi=10.1038/sj.icb.7100140|pmid=18040281}}</ref> The first experimental evidence came in 1958, when [[Gustav Nossal]] and [[Joshua Lederberg]] showed that one B cell always produces only one antibody.<ref name=nossal>{{cite journal|last=Nossal|first=G. J. V.|author2=Lederberg, Joshua|title=Antibody Production by Single Cells|journal=Nature|year=1958|volume=181|issue=4620|pages=1419–1420|doi=10.1038/1811419a0|pmid=13552693|pmc=2082245}}</ref> The idea turned out to be the foundation of molecular immunology, especially in [[adaptive immunity]].<ref>{{cite journal|last=Medzhitov|first=R.|title=Pattern Recognition Theory and the Launch of Modern Innate Immunity|journal=The Journal of Immunology|year=2013|volume=191|issue=9|pages=4473–4474|pmid=24141853|doi=10.4049/jimmunol.1302427}}</ref>
The theory states that in a pre-existing group of lymphocytes (both B and T cells), a specific antigen activates (i.e. selects) only its counter-specific cell, which then induces that particular cell to multiply, producing identical [[Clone (B-cell biology)|clones]] for antibody production. This activation occurs in secondary lymphoid organs such as the [[spleen]] and the [[lymph node]]s.<ref>{{Cite book|title = Janeway's Immunobiology 8th Edition|last = Murphy|first = Kenneth|publisher = Garland Science|year = 2012|isbn = 9780815342434|location = New York, NY}}</ref> In short, the theory is an explanation of the mechanism for the generation of diversity of antibody specificity.<ref name="Jordan 2007 72–79">{{cite journal|last=Jordan|first=Margaret A|author2=Baxter, Alan G|title=Quantitative and qualitative approaches to GOD: the first 10 years of the clonal selection theory|journal=Immunology and Cell Biology|year=2007|volume=86|issue=1|pages=72–79|doi=10.1038/sj.icb.7100140|pmid=18040281|s2cid=19122290}}</ref> The first experimental evidence came in 1958, when [[Gustav Nossal]] and [[Joshua Lederberg]] showed that one B cell always produces only one antibody.<ref name=nossal>{{cite journal|last=Nossal|first=G. J. V.|author2=Lederberg, Joshua|title=Antibody Production by Single Cells|journal=Nature|year=1958|volume=181|issue=4620|pages=1419–1420|doi=10.1038/1811419a0|pmid=13552693|pmc=2082245|bibcode=1958Natur.181.1419N }}</ref> The idea turned out to be the foundation of molecular immunology, especially in [[adaptive immunity]].<ref>{{cite journal|last=Medzhitov|first=R.|title=Pattern Recognition Theory and the Launch of Modern Innate Immunity|journal=The Journal of Immunology|year=2013|volume=191|issue=9|pages=4473–4474|pmid=24141853|doi=10.4049/jimmunol.1302427|doi-access=free}}</ref>


==Postulates==
==Postulates==

The clonal selection theory can be summarised with the following four tenets:
The clonal selection theory can be summarised with the following four tenets:
* Each lymphocyte bears a single type of receptor with a unique specificity (by [[V(D)J recombination]]).
* Each lymphocyte bears a single type of receptor with a unique specificity (generated by [[V(D)J recombination]]).
* Receptor occupation is required for cell activation.
* Receptor occupation is required for cell activation.
* The differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity as the parental cell.
* The differentiated [[effector cell]]s derived from an activated lymphocyte bear receptors of identical specificity as the parent cell.
* Those lymphocytes bearing receptors for self molecules will be destroyed at an early stage.
* Those lymphocytes bearing receptors for self molecules (i.e., [[endogenous]] antigens produced within the body) are destroyed at an early stage.


==Early work==
==Early work==
In 1900, [[Paul Ehrlich]] proposed the so-called side chain theory of antibody production. According to it, certain cells exhibit on their surface different "side chains" (i.e. membrane-bound antibodies) able to react with different antigens. When an antigen comes, it binds to a matching side chain. Then the cell stops producing all other side chains and starts intensive synthesis and secretion of the antigen-binding side chain as a soluble antibody. This was a selection (though not clonal selection) theory far more accurate than the instructive theories that dominated immunology in the next decades.
In 1900, [[Paul Ehrlich]] proposed the so-called "side chain theory" of antibody production. According to it, certain cells exhibit on their surface different "[[side chain]]s" (i.e. membrane-bound antibodies) able to react with different antigens. When an antigen is present, it binds to a matching side chain. Then the cell stops producing all other side chains and starts intensive synthesis and secretion of the antigen-binding side chain as a soluble antibody. Though distinct from clonal selection, Ehrlich's idea was a selection theory far more accurate than the instructive theories that dominated immunology in the next decades.


In 1955, Danish immunologist [[Niels Jerne]] put forward a hypothesis that there is already a vast array of soluble antibodies in the serum prior to any infection. The entrance of an antigen into the body results in the selection of only one type of antibody to match it. This may happen by certain cells phagocytosing the immune complexes and somehow replicating the antibody structure to produce more of it.<ref name="Burnet1976">{{cite journal|last1=Burnet|first1=F. M.|title=A Modification of Jerne's Theory of Antibody Production using the Concept of Clonal Selection|journal=CA: A Cancer Journal for Clinicians|volume=26|issue=2|year=1976|pages=119–121|issn=0007-9235|doi=10.3322/canjclin.26.2.119|pmid=816431}}</ref>
In 1955, Danish immunologist [[Niels Jerne]] put forward a hypothesis that there is already a vast array of soluble antibodies in the [[blood serum|serum]] prior to any infection. The entrance of an antigen into the body results in the selection of only one type of antibody to match it. This supposedly occurred by certain cells [[phagocytosis|phagocytosing]] the immune complexes and somehow replicating the antibody structure to produce more of it.<ref name="Burnet1976">{{cite journal|last1=Burnet|first1=F. M.|title=A Modification of Jerne's Theory of Antibody Production using the Concept of Clonal Selection|journal=CA: A Cancer Journal for Clinicians|volume=26|issue=2|year=1976|pages=119–121|issn=0007-9235|doi=10.3322/canjclin.26.2.119|pmid=816431|s2cid=40609269|doi-access=free}}</ref>


In 1957, [[David W. Talmage]] hypothesized that antigens bind to antibodies on the surface of antibody-producing cells and "only those cells are selected for multiplication whose synthesized product has affinity for the antigen". The key difference from Ehrlich's theory was that every cell was presumed to synthesize only one sort of antibody. After antigen binding the cell proliferates, forming clones with identical antibodies.
==Further work==
In 1957, [[David W. Talmage]] hypothesized that antigens bind to antibodies on the surface of antibody-producing cells and "only those cells are selected for multiplication whose synthesized product has affinity for the antigen". The key difference from Ehrlich's theory was that every cell was presumed to synthesize only one sort of antibody. After antigen binding the cell proliferates, forming a clone producing the same antibody.


===Burnet's clonal selection theory===
===Burnet's clonal selection theory===
Later in 1957, Australian immunologist [[Frank Macfarlane Burnet]] published a paper titled "A modification of Jerne's theory of antibody production using the concept of clonal selection" in the rather obscure ''Australian Journal of Science''. In it Burnet expanded the ideas of Talmage and named the resulting theory the "clonal selection theory". He further formalised the theory in his 1959 book ''The Clonal Selection Theory of Acquired Immunity''. He explained [[immunological memory]] as the cloning of two types of lymphocyte. One clone acts immediately to combat infection whilst the other is longer lasting, remaining in the immune system for a long time and causing immunity to that antigen. According to Burnet's hypothesis, among antibodies are molecules that can probably correspond with varying degrees of precision to all, or virtually all, the [[antigenic determinant]]s that occur in biological material other than those characteristic of the body itself. Each type of pattern is a specific product of a clone of lymphocytes and it is the essence of the hypothesis that each cell automatically has available on its surface representative reactive sites equivalent to those of the [[globulin]] they produce. When an antigen enters the blood or tissue fluids it is assumed that it will attach to the surface of any lymphocyte carrying reactive sites that correspond to one of its antigenic determinants. Then the cell is activated and undergoes proliferation to produce a variety of descendants. In this way, preferential proliferation is initiated of all those clones whose reactive sites correspond to the antigenic determinants on the antigens present in the body. The descendants are capable of active liberation of soluble antibody and lymphocytes, the same functions as the parental forms.<ref name="Jordan 2007 72–79"/><ref>{{cite journal|last=Hodgkin|first=Philip D|author2=Heath, William R |author3=Baxter, Alan G |title=The clonal selection theory: 50 years since the revolution|journal=Nature Immunology|year=2007|volume=8|issue=10|pages=1019–1026|doi=10.1038/ni1007-1019|pmid=17878907|s2cid=29935594}}</ref>


In 1958, [[Gustav Nossal]] and [[Joshua Lederberg]] showed that one B cell always produces only one antibody, which was the first direct evidence supporting the clonal selection theory.<ref name=nossal/>
Later in the same year, Australian immunologist [[Frank Macfarlane Burnet]] published a paper titled ‘A modification of Jerne's theory of antibody production using the concept of clonal selection’ in a rather obscure ''Australian Journal of Science''. In it Burnet expanded the ideas of Talmage and named it "clonal selection theory." He further formalised the theory in his 1959 book ''The Clonal Selection Theory of Acquired Immunity''. He explained immunological memory as the cloning of two types of lymphocyte. One clone acts immediately to combat infection whilst the other is longer lasting, remaining in the immune system for a long time, which results in immunity to that antigen. According to Burnet's hypothesis among antibodies are molecules that can correspond probably with varying degrees of precision to all, or virtually all, the [[antigenic determinant]]s that occur in biological material other than that characteristic of the body itself. Each type of pattern is a specific product of a clone of lymphocytes and it is the essence of the hypothesis that each cell automatically has available on its surface representative reactive sites equivalent to those of the globulin they produce. When an antigen enters the blood or tissue fluids it is assumed that it will attach to the surface of any lymphocyte carrying reactive sites which correspond to one of its antigenic determinants. Then the cell is activated and undergo proliferation to produce a variety of descendents. In this way, preferential proliferation will be initiated of all those clones whose reactive sites correspond to the antigenic determinants on the antigen used. The descendents will be capable of active liberation of soluble antibody and lymphocytes which can fulfil the same functions as the parental forms.<ref name="Jordan 2007 72–79"/><ref>{{cite journal|last=Hodgkin|first=Philip D|author2=Heath, William R |author3=Baxter, Alan G |title=The clonal selection theory: 50 years since the revolution|journal=Nature Immunology|year=2007|volume=8|issue=10|pages=1019–1026|doi=10.1038/ni1007-1019|pmid=17878907}}</ref>

In 1958, [[Gustav Nossal]] and [[Joshua Lederberg]] showed that one B cell always produces only one antibody, which was the first evidence for clonal selection theory.<ref name=nossal/>


==Theories supported by clonal selection==
==Theories supported by clonal selection==
Burnet and [[Peter Medawar]] worked together on understanding immunological tolerance, a phenomenon also explained by clonal selection. This is the organism’s ability to tolerate the introduction of cells without an immune response as long as this occurs early in the organism’s development. There are a vast number of lymphocytes occurring in the immune system ranging from cells which are tolerant of self tissue to cells which are not tolerant of self tissue. However, only cells that are tolerant to self tissue will survive the embryonic stage. If non-self tissue is introduced, the lymphocytes which develop will be the ones which included the non-self tissues as self tissue.
Burnet and [[Peter Medawar]] worked together on understanding [[immunological tolerance]], a phenomenon also explained by clonal selection. This is the organism's ability to tolerate the introduction of cells prior to the development of an immune response as long as it occurs early in the organism's development. There are a vast number of lymphocytes occurring in the immune system, ranging from cells that tolerate self tissue to cells that do not. However, only cells tolerant of self tissue survive the embryonic stage. If non-self tissue is introduced, lymphocytes that develop are the ones that include the non-self tissues as self tissue.


In 1959 Burnet proposed that under certain circumstances, tissues could be successfully transplanted into foreign recipients. This work has led to a much greater understanding of the immune system and also great advances in tissues transplantation. Burnet and Medawar shared the [[Nobel Prize in Physiology or Medicine]] in 1960.
In 1959, Burnet proposed that under certain circumstances, tissues could be successfully transplanted into foreign recipients. This work has led to a much greater understanding of the immune system and also great advances in tissue transplantation. Burnet and Medawar shared the [[Nobel Prize in Physiology or Medicine]] in 1960.


In 1974 [[Niels Kaj Jerne]] proposed that the immune system functions as a network, that is regulated via interactions between the variable parts of lymphocytes and their secreted molecules. [[Immune network theory]] is firmly based on the concept of clonal selection. Jerne won the Nobel Prize in Physiology or Medicine in 1984, largely for his contributions to immune network theory.
In 1974, [[Niels Kaj Jerne]] proposed that the immune system functions as a network that is regulated via interactions between the variable parts of lymphocytes and their secreted molecules. [[Immune network theory]] is firmly based on the concept of clonal selection. Jerne won the Nobel Prize in Physiology or Medicine in 1984, largely for his contributions to immune network theory.


==See also==
==See also==
* [[Adaptive immune system]]
* [[Adaptive immune system]]
* [[Clonal selection algorithm]]
* [[Clonal selection algorithm]]
* [[Immune system]]
* [[Universal Darwinism]]
* [[Universal Darwinism]]


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==Further reading==
==Further reading==
*{{cite book|last=Podolsky|first=Alfred I. Tauber; Scott H.|title=The Generation of Diversity : Clonal Selection Theory and the Rise of Molecular Immunology|year=2000|publisher=Harvard Univ. Press|location=Cambridge, Massachusetts |isbn=0-674-00182-6|url=https://books.google.com/books?id=ul2nIQjK2pwC&source|edition=1st paperback}}
*{{cite book|last=Podolsky|first=Alfred I. Tauber; Scott H.|title=The Generation of Diversity : Clonal Selection Theory and the Rise of Molecular Immunology|year=1997|publisher=Harvard Univ. Press|location=Cambridge, Massachusetts |isbn=0-674-00182-6|url=https://books.google.com/books?id=ul2nIQjK2pwC|edition=1st paperback}}
*"Biology in Context - The Spectrum of Life" Authors, Peter Aubusson, Eileen Kennedy.
*"Biology in Context - The Spectrum of Life" Authors, Peter Aubusson, Eileen Kennedy.
*{{cite journal | author = Forsdyke D.R. | year = 1995 | title = The Origins of the Clonal Selection Theory of Immunity | url = http://post.queensu.ca/~forsdyke/theorimm0.htm#Introduction | journal = FASEB Journal | volume = 9 | issue = | pages = 164–66 }}
*{{cite journal | author = Forsdyke D.R. | year = 1995 | title = The Origins of the Clonal Selection Theory of Immunity | journal = FASEB Journal | volume = 9 | issue = 2 | pages = 164–66 | doi = 10.1096/fasebj.9.2.7781918 | doi-access = free | pmid = 7781918 | s2cid = 38467403 }}


==External links==
==External links==
* [http://www.wehi.edu.au/education/wehitv/the_immune_system/ Animation of clonal selection] from the Walter & Elisa Hall institute.
* [http://www.wehi.edu.au/education/wehitv/the_immune_system/ Animation of clonal selection] {{Webarchive|url=https://web.archive.org/web/20110706121622/http://wehi.edu.au/education/wehitv/the_immune_system/ |date=6 July 2011 }} from the Walter & Elisa Hall institute.


{{Portal bar|Biology|Medicine}}
{{Portal bar|Biology|Medicine}}

{{Lymphocytic immune system}}
{{Lymphocytic immune system}}



Latest revision as of 01:48, 26 March 2024

Clonal selection theory of lymphocytes:
1) A hematopoietic stem cell undergoes differentiation and genetic rearrangement to produce
2) immature lymphocytes with many different antigen receptors. Those that bind to
3) antigens from the body's own tissues are destroyed, while the rest mature into
4) inactive lymphocytes. Most of these never encounter a matching
5) foreign antigen, but those that do are activated and produce
6) many clones of themselves.

In immunology, clonal selection theory explains the functions of cells of the immune system (lymphocytes) in response to specific antigens invading the body. The concept was introduced by Australian doctor Frank Macfarlane Burnet in 1957, in an attempt to explain the great diversity of antibodies formed during initiation of the immune response.[1][2] The theory has become the widely accepted model for how the human immune system responds to infection and how certain types of B and T lymphocytes are selected for destruction of specific antigens.[3]

The theory states that in a pre-existing group of lymphocytes (both B and T cells), a specific antigen activates (i.e. selects) only its counter-specific cell, which then induces that particular cell to multiply, producing identical clones for antibody production. This activation occurs in secondary lymphoid organs such as the spleen and the lymph nodes.[4] In short, the theory is an explanation of the mechanism for the generation of diversity of antibody specificity.[5] The first experimental evidence came in 1958, when Gustav Nossal and Joshua Lederberg showed that one B cell always produces only one antibody.[6] The idea turned out to be the foundation of molecular immunology, especially in adaptive immunity.[7]

Postulates

[edit]

The clonal selection theory can be summarised with the following four tenets:

  • Each lymphocyte bears a single type of receptor with a unique specificity (generated by V(D)J recombination).
  • Receptor occupation is required for cell activation.
  • The differentiated effector cells derived from an activated lymphocyte bear receptors of identical specificity as the parent cell.
  • Those lymphocytes bearing receptors for self molecules (i.e., endogenous antigens produced within the body) are destroyed at an early stage.

Early work

[edit]

In 1900, Paul Ehrlich proposed the so-called "side chain theory" of antibody production. According to it, certain cells exhibit on their surface different "side chains" (i.e. membrane-bound antibodies) able to react with different antigens. When an antigen is present, it binds to a matching side chain. Then the cell stops producing all other side chains and starts intensive synthesis and secretion of the antigen-binding side chain as a soluble antibody. Though distinct from clonal selection, Ehrlich's idea was a selection theory far more accurate than the instructive theories that dominated immunology in the next decades.

In 1955, Danish immunologist Niels Jerne put forward a hypothesis that there is already a vast array of soluble antibodies in the serum prior to any infection. The entrance of an antigen into the body results in the selection of only one type of antibody to match it. This supposedly occurred by certain cells phagocytosing the immune complexes and somehow replicating the antibody structure to produce more of it.[8]

In 1957, David W. Talmage hypothesized that antigens bind to antibodies on the surface of antibody-producing cells and "only those cells are selected for multiplication whose synthesized product has affinity for the antigen". The key difference from Ehrlich's theory was that every cell was presumed to synthesize only one sort of antibody. After antigen binding the cell proliferates, forming clones with identical antibodies.

Burnet's clonal selection theory

[edit]

Later in 1957, Australian immunologist Frank Macfarlane Burnet published a paper titled "A modification of Jerne's theory of antibody production using the concept of clonal selection" in the rather obscure Australian Journal of Science. In it Burnet expanded the ideas of Talmage and named the resulting theory the "clonal selection theory". He further formalised the theory in his 1959 book The Clonal Selection Theory of Acquired Immunity. He explained immunological memory as the cloning of two types of lymphocyte. One clone acts immediately to combat infection whilst the other is longer lasting, remaining in the immune system for a long time and causing immunity to that antigen. According to Burnet's hypothesis, among antibodies are molecules that can probably correspond with varying degrees of precision to all, or virtually all, the antigenic determinants that occur in biological material other than those characteristic of the body itself. Each type of pattern is a specific product of a clone of lymphocytes and it is the essence of the hypothesis that each cell automatically has available on its surface representative reactive sites equivalent to those of the globulin they produce. When an antigen enters the blood or tissue fluids it is assumed that it will attach to the surface of any lymphocyte carrying reactive sites that correspond to one of its antigenic determinants. Then the cell is activated and undergoes proliferation to produce a variety of descendants. In this way, preferential proliferation is initiated of all those clones whose reactive sites correspond to the antigenic determinants on the antigens present in the body. The descendants are capable of active liberation of soluble antibody and lymphocytes, the same functions as the parental forms.[5][9]

In 1958, Gustav Nossal and Joshua Lederberg showed that one B cell always produces only one antibody, which was the first direct evidence supporting the clonal selection theory.[6]

Theories supported by clonal selection

[edit]

Burnet and Peter Medawar worked together on understanding immunological tolerance, a phenomenon also explained by clonal selection. This is the organism's ability to tolerate the introduction of cells prior to the development of an immune response as long as it occurs early in the organism's development. There are a vast number of lymphocytes occurring in the immune system, ranging from cells that tolerate self tissue to cells that do not. However, only cells tolerant of self tissue survive the embryonic stage. If non-self tissue is introduced, lymphocytes that develop are the ones that include the non-self tissues as self tissue.

In 1959, Burnet proposed that under certain circumstances, tissues could be successfully transplanted into foreign recipients. This work has led to a much greater understanding of the immune system and also great advances in tissue transplantation. Burnet and Medawar shared the Nobel Prize in Physiology or Medicine in 1960.

In 1974, Niels Kaj Jerne proposed that the immune system functions as a network that is regulated via interactions between the variable parts of lymphocytes and their secreted molecules. Immune network theory is firmly based on the concept of clonal selection. Jerne won the Nobel Prize in Physiology or Medicine in 1984, largely for his contributions to immune network theory.

See also

[edit]

References

[edit]
  1. ^ Burnet, FM (1976). "A modification of Jerne's theory of antibody production using the concept of clonal selection". CA: A Cancer Journal for Clinicians. 26 (2): 119–21. doi:10.3322/canjclin.26.2.119. PMID 816431. S2CID 40609269.
  2. ^ Cohn, Melvin; Av Mitchison, N.; Paul, William E.; Silverstein, Arthur M.; Talmage, David W.; Weigert, Martin (2007). "Reflections on the clonal-selection theory". Nature Reviews Immunology. 7 (10): 823–830. doi:10.1038/nri2177. PMID 17893695. S2CID 24741671.
  3. ^ Rajewsky, Klaus (1996). "Clonal selection and learning in the antibody system". Nature. 381 (6585): 751–758. Bibcode:1996Natur.381..751R. doi:10.1038/381751a0. ISSN 0028-0836. PMID 8657279. S2CID 4279640.
  4. ^ Murphy, Kenneth (2012). Janeway's Immunobiology 8th Edition. New York, NY: Garland Science. ISBN 9780815342434.
  5. ^ a b Jordan, Margaret A; Baxter, Alan G (2007). "Quantitative and qualitative approaches to GOD: the first 10 years of the clonal selection theory". Immunology and Cell Biology. 86 (1): 72–79. doi:10.1038/sj.icb.7100140. PMID 18040281. S2CID 19122290.
  6. ^ a b Nossal, G. J. V.; Lederberg, Joshua (1958). "Antibody Production by Single Cells". Nature. 181 (4620): 1419–1420. Bibcode:1958Natur.181.1419N. doi:10.1038/1811419a0. PMC 2082245. PMID 13552693.
  7. ^ Medzhitov, R. (2013). "Pattern Recognition Theory and the Launch of Modern Innate Immunity". The Journal of Immunology. 191 (9): 4473–4474. doi:10.4049/jimmunol.1302427. PMID 24141853.
  8. ^ Burnet, F. M. (1976). "A Modification of Jerne's Theory of Antibody Production using the Concept of Clonal Selection". CA: A Cancer Journal for Clinicians. 26 (2): 119–121. doi:10.3322/canjclin.26.2.119. ISSN 0007-9235. PMID 816431. S2CID 40609269.
  9. ^ Hodgkin, Philip D; Heath, William R; Baxter, Alan G (2007). "The clonal selection theory: 50 years since the revolution". Nature Immunology. 8 (10): 1019–1026. doi:10.1038/ni1007-1019. PMID 17878907. S2CID 29935594.

Further reading

[edit]
[edit]