TY - JOUR
T1 - IMMUNOPHARMACOLOGICAL DISEASE
T2 - A BREAK IN TOLERANCE TO RECEPTOR SITES
AU - Lennon, Vanda A.
AU - Carnegie, Patrick R.
PY - 1971/3/27
Y1 - 1971/3/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0015241947&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0015241947&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(71)91557-1
DO - 10.1016/S0140-6736(71)91557-1
M3 - Article
C2 - 4101235
AN - SCOPUS:0015241947
VL - 297
SP - 630
EP - 633
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 7700
ER -