Editing Side-chain theory

{{Short description|Generally accepted theory published in 1900 to explain immune response in living cells}}
The '''side-chain theory''' ([[German language|German]], '''''Seitenkettentheorie''''') is a [[theory]] proposed by [[Paul Ehrlich]] (1854&ndash;1915) to explain the [[immune response]] in living [[cell (biology)|cell]]s. Ehrlich theorized from very early in his career that [[chemical structure]] could be used to explain why the immune response occurred in reaction to [[infection]]. He believed that [[toxin]]s and [[antitoxin]]s were [[chemical substance]]s at a time when very little was known about their nature. The theory explains the interaction of antibodies and antigens in the blood, and how antibodies are produced.<ref name="wite">{{cite journal|last1=Witebsky|first1=Ernest|title=Ehrlich's side-chain theory in the light of present immunology|journal=Annals of the New York Academy of Sciences|date=1954|volume=59|issue=2|pages=168–181|doi=10.1111/j.1749-6632.1954.tb45929.x|pmid=13229205|bibcode=1954NYASA..59..168W }}</ref>

==History==

In 1891, Paul Ehrlich joined the newly established [[Robert Koch Institute]] in Berlin upon the invitation of [[Robert Koch]] himself.<ref>{{cite journal|last1=Kasten|first1=FH|title=Paul Ehrlich: pathfinder in cell biology. 1. Chronicle of his life and accomplishments in immunology, cancer research, and chemotherapy.|journal=Biotechnic & Histochemistry|year=1996|volume=71|issue=1|pages=2–37|pmid=9138526|doi=10.3109/10520299609117128}}</ref> By 1896 a new branch, the Institute for Serum Research and Testing (Institut für Serumforschung und Serumprüfung), was established in Frankfurt with Ehrlich as its founding director.<ref>{{cite journal|last1=Valent|first1=Peter|last2=Groner|first2=Bernd|last3=Schumacher|first3=Udo|last4=Superti-Furga|first4=Giulio|last5=Busslinger|first5=Meinrad|last6=Kralovics|first6=Robert|last7=Zielinski|first7=Christoph|last8=Penninger|first8=Josef M.|last9=Kerjaschki|first9=Dontscho|last10=Stingl|first10=Georg|last11=Smolen|first11=Josef S.|last12=Valenta|first12=Rudolf|last13=Lassmann|first13=Hans|last14=Kovar|first14=Heinrich|last15=Jäger|first15=Ulrich|last16=Kornek|first16=Gabriela|last17=Müller|first17=Markus|last18=Sörgel|first18=Fritz|title=Paul Ehrlich (1854-1915) and His Contributions to the Foundation and Birth of Translational Medicine|journal=Journal of Innate Immunity|year=2016|volume=8|issue=2|pages=111–20|doi=10.1159/000443526|pmid=26845587|pmc=6738855 |doi-access=free}}</ref> He worked on antitoxins for [[diphtheria]] and their binding to antibodies in the blood. He hypothesised that antibodies bind to antigens through special chemical structures that he called "side chains" (which he later named "receptors"). Borrowing a concept used by [[Hermann Emil Fischer|Emil Fischer]] in 1894 to explain the interaction between an enzyme and its substrate, Ehrlich proposed that binding of the receptor to an infectious agent was like the fit between a lock and key. He published the first part of his side-chain theory in 1897, and its full form in 1900 in a lecture he delivered to the [[Royal Society]] in London.<ref name="ziel">{{cite journal|last1=Zielinska|first1=Edyta|title=Side-Chain Theory, circa 1900|journal=The Scientist|year=2013|volume=online|url=http://www.the-scientist.com/?articles.view/articleNo/36175/title/Side-Chain-Theory--circa-1900/}}</ref>

==Postulate==

Ehrlich's theory can be summarised with the following tenets:<ref>{{cite book|last1=Silverstein|first1=Arthur M|title=A History of Immunology|date=1989|publisher=Elsevier Science|location=Oxford|isbn=978-0-080925837|page=95|url=https://books.google.com/books?id=J3Hg4I6GrYoC}}</ref>
# Antibodies are produced by white blood cells normally and they act as side chains (receptors) on the cell membrane.
# Antibody specificity exists for specific interaction with a given antigen.
# Antigen–antibody interaction occurs by precise binding through the side chains.

==Concept==
[[File:Diagrams illustrating the side-chain theory of Paul Ehrlich Wellcome M0013303.jpg|frameless|right]]
[[File:Diagrams illustrating the side-chain theory of Paul Ehrlich Wellcome M0013304.jpg|frameless|right]]
Ehrlich supposed that living cells have [[side chain]]s in the same way [[dyes]] have side chains which are related to their coloring properties. These side chains can link with a particular toxin (or any antigen), just as Emil Fischer said [[enzymes]] must bind to their [[receptor (biochemistry)|receptor]]s "as lock and key."<ref>{{cite book|last1=Kindt|first1=Thomas J.|last2=Capra|first2=J. Donald|title=The Antibody Enigma|date=1984|publisher=Springer US|location=Boston, MA|isbn=978-1-46844676-0|page=6|url=https://books.google.com/books?id=VBcGCAAAQBAJ}}</ref>

Ehrlich theorised that a cell under threat grew additional side chains to bind the toxin, and that these additional side chains broke off to become the [[antibody|antibodies]] that are circulated through the body. According to this theory, the surface of white blood cells is covered with many side chains that form chemical links with the antigens. For any given antigen, at least one of these side chains would bind, stimulating the cell to produce more of the same type, which would then be liberated into the blood stream as antibodies. According to Ehrlich, an antibody could be considered an irregularly shaped, microscopic, three-dimensional label that would bind to a specific antigen but not to the other cells of the organism. It was these antibodies that Ehrlich first described as "[[Magic bullet (medical)|magic bullets]]", agents that specifically target toxins or pathogens without harming the body.<ref>{{cite journal|last1=Tan|first1=SY|last2=Grimes|first2=S|title=Paul Ehrlich (1854-1915): man with the magic bullet|journal=Singapore Medical Journal|year=2010|volume=51|issue=11|pages=842–843|pmid=21140107|url=http://smj.sma.org.sg/5111/5111ms1.pdf}}</ref><ref>{{cite journal|last1=Chuaire|first1=Lilian|last2=Cediel|first2=Juan Fernando|title=Paul Ehrlich: From magic bullets to chemotherapy|journal=Colombia Médica|year=2009|volume=39|issue=3|page=online|url=http://colombiamedica.univalle.edu.co/index.php/comedica/article/view/597/902#4}}</ref>

Ehrlich suggested that interaction between an infectious agent and a cell-bound receptor would induce the cell to produce and release more receptors with the same specificity. According to Ehrlich’s theory, the specificity of the receptor was determined before its exposure to antigen, and the antigen selected the appropriate receptor. Ultimately all aspects of Ehrlich's theory would be proven correct with the minor exception that the "receptor" exists as both a soluble antibody molecule and as a cell-bound receptor; it is the soluble form that is secreted rather than the bound form released.

==See also==
*''[[Dr. Ehrlich's Magic Bullet]]'', a 1940 film
*[[Diphtheria]]
*[[Syphilis]]

==References==
{{Reflist}}

==Further reading==
*{{cite book|last1=Silverstein|first1=Arthur M.|title=Paul Ehrlich's Receptor Immunology the Magnificent Obsession|year=2001|publisher=Elsevier|location=Burlington|isbn=978-0-080538518|url=https://books.google.com/books?id=59u9tTd8grQC|pages=202}}
*{{cite journal|last1=Günther|first1=O|title=Changes in Ehrlich's side-chain theory|journal=Deutsche Medizinische Wochenschrift|year=1966|volume=91|issue=26|pages=1197–1201|pmid=5328273|language=German|doi=10.1055/s-0028-1110731}}
*{{cite journal|last1=Anonymous|title=Membranes, receptors, and the immune response. 80 years after Ehrlich's side chain theory|journal=Progress in Clinical and Biological Research|year=1980|volume=42|issue=1|pages=1–387|pmid=7393927}}
*{{cite journal|last1=Doerr|first1=HW|title=Paul Ehrlich's concept of immune defense|journal=Deutsche Medizinische Wochenschrift|year=1996|volume=121|issue=30|pages=958–961|doi=10.1055/s-0029-1233819|pmid=8765706|language=German}}
*{{cite journal|last1=Silverstein|first1=AM|title=Paul Ehrlich's passion: the origins of his receptor immunology|journal=Cellular Immunology|year=1999|volume=194|issue=2|pages=213–221|doi=10.1006/cimm.1999.1505|pmid=10383824|doi-access=free}}
*{{cite journal|last1=Prüll|first1=CR|title=Part of a scientific master plan? Paul Ehrlich and the origins of his receptor concept|journal=Medical History|year=2003|volume=47|issue=3|pages=332–356|doi=10.1017/S0025727300057045|pmid=12905918|pmc=1044632}}

{{DEFAULTSORT:Side-Chain Theory}}
[[Category:Immunology theories]]
[[Category:Paul Ehrlich]]