Side-chain theory

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Paul Ehrlich

Side-chain theory (German, Seitenkettentheorie) is a theory proposed by Paul Ehrlich (1854–1915) to explain the immune response in living cells. 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 toxins and antitoxins were chemical substances at a time when very little was known about their nature.

Ehrlich supposed that living cells have side-chains in the same way dyes have side-chains which are related to their coloring properties. These side chains can link with a particular toxin, just as Emil Fischer said enzymes must bind to their receptors "like a key in a lock."

Ehrlich theorized that a cell under threat grew additional side-chains to bind the toxin, and that these additional side chains broke off to become the antibodies that are circulated through the body. It was these antibodies that Ehrlich first described as "magic bullets" in search of toxins.

In an attempt to explain the origin of serum antibody, Ehrlich proposed that cells in the blood expressed a variety of receptors, which he called “side-chain receptors,” that could react with infectious agents and inactivate them. Borrowing a concept used by 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. 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. Reference(Kuby Immunology)

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