IMMUNOPHARMACOLOGICAL DISEASE: A BREAK IN TOLERANCE TO RECEPTOR SITES

Vanda A Lennon, PatrickR Carnegie

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

This hypothesis invokes a new pathophysiological process to explain functional lesions in certain organ-specific autoimmune diseases. It is suggested that a pathogenic immune response can be directed against exposed cell-membrane receptor sites for humoral agents such as neurotransmitters or peptide hormones, and that interaction of an antibody or immunocyte with the receptor site causes an " immunopharmacological" block which disrupts the normal function of that cell and related cells. Tissue damage would result either from the ensuing inflammatory response, initiated by the immunological interaction with the tissue receptor(s), or from disuse atrophy of the unstimulated target cells. This hypothesis was developed from studies in experimental autoimmune encephalomyelitis (E.A.E.) and could be applicable to human multiple sclerosis. The autoantigen responsible for inducing E.A.E. is the small" tryptophan peptide" isolated from the basic protein of myelin, and apparently present also in membranes of nerve-endings. The three-dimensional structure of the tryptophan peptide fulfils the calculated requirement for a central-nervous-system receptor site for 5-hydroxytryptamine (5-H.T.). Antibody to the peptide would compete with 5-H.T. for the receptor site. The concept of functional failure due to immuno-pharmacological block is applicable to other diseases with abnormal immunological features including myasthenia gravis, with its characteristic motor end-plate lesion, and autoimmune diseases of secretory organs. The postulated functionally disruptive autoantibodies may be detectable better by physiological test systems than by conventional immunological tests.

Original languageEnglish (US)
Pages (from-to)630-633
Number of pages4
JournalThe Lancet
Volume297
Issue number7700
DOIs
StatePublished - Mar 27 1971
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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