- Email: [email protected]
SKIN-GRAFTING OF FINGERTIP INJURIES
1110 chains of M.c.p. and its related T.c.F. are coded by the same genes,24 and mututal M.C.P.-T.C.F. recognition involves London self-recognition forces. Following J erne,5 we have suggested that the first of a sequence of multiple steps in classical immunity is the combination of the antigen (Ag) with pre-formed immunoglobulin antibody (Ab) circulating in the body-fluids.2 The combination of Ag with Ab produces an allosteric modification of the latter, and this provides a signal to reticular and macrophagic cells. These cells take up the Ag-Ab complex, and in the " primary response the Ab (not Ag) is processed for presentation to initially uncommitted multi-potential cells, to induce the synthesis of Abs of the same specificity.2 An essential requirement for the classical immune response in the Jeme5 model, is the existence of opsonins or preformed Abs (e.g., IgM or IgG) complementary to the challenge Ags. However, humoral T.C.F.s should have a similar protein structure to Abs, although their non-protein lipid component differs from that of immunoglobulins and humoral M.C.p.s, which are complexed with carbohydrates. Hypersensitivity, " we suggest, requires firstly, an antigen " that will combine effectively with a specific humoral T.C.F., and, secondly, the existence in the host of an autoantibody (mutant M.c.p.) that is complementary to the same T.C.F. The Ag-T.C.F. complex interferes with the afferent control of the release of the mutant M.c.p., which in consequence is liberated at high concentration to attack the target tissue bearing the specific T.c.F. Direct Ag-autoantibody interactions will also occur. When the autoantibody (mutant M.c.p.) is humoral, the reaction is immediate hypersensitivity; when the autoantibody is cellular (a mutant small lymphocyte) delayed hypersensitivity results. (We have suggested2 that some humoral M.c.p.s may be "
synthesised by mast cells.) In the homograft situation, many of the T.C.F.s of the allogeneic graft will usually be complementary to host T.C.F.s and M.c.p.s. Combination between graft and host T.C.F.s will produce an accelerated discharge of host M.c.p.s, complementary to the cellular T.C.F.S of the graft. If the graft includes tissues that are normally under the control of humoral and
diminished by regarding it as non-immunological. It is not enough to suggest that lymphocytes recognise and destroy allogeneic cells by virtue of characteristics which are distinct from histocompatibility differences-a plausible alternative is
required. The failure of Dr. Fikrig and his colleagues to demonstrate lymphocyte blastogenesis due to trophoblast may well be yet another instance of the unreliability of the mixed-lymphocyteculture technique.Although no technical details were given, it is possible that lysis of trophoblast would release intracellular acidic mucopolysaccharides into the medium. These are known to coat cells in vitroand to inhibit blastogenesis in mixed lymphocyte cultures at very low concentrations.In any case, the cytotoxic effects of non-immune lymphocytes do not appear to be dependent upon blastic transformation in the allogeneic inhibition system. The effects are still present when the lymphocytes have been heavily irradiated.6 We suggest that an adequate discussion of this problem will only be possible when the experimental methods of Dr, Fikrig’s group, and ours, have been published. Edgar and Tenovus Laboratories, Charing Cross Group of Hospitals, Fulham
Hospital,
London W.6.
G. A. CURRIE K. D. BAGSHAWE.
SKIN-GRAFTING OF FINGERTIP INJURIES SIR,-I was interested to read Dr. Salaman’s paper (April 1, p. 705) and glad to see that you accorded it an annotation, for the subject is of particular interest and importance to all who work in casualty departments. Might I with all humility suggest a solution to the dilemma of split versus full thickness skin-grafts for these injuries, which is, like many British answers to
surgical problems, a compromise ? cutting domed grafts which were almost centre and split at the periphery, using a
In 1942 I started full thickness at the
cellular M.c.p.s, then both humoral and cellular factors will be involved in graft rejection. Damaged graft T.c.F.s should also combine with host immunoglobulins,2 and hence graft rejection will be accompanied by a classical (immunoglobulin) immune reaction. It follows that, if the host-versus-graft response can be adequately suppressed, then the graft should eventually fail not through immune rejection but through the loss of -cells. Normally, the stem-cell loss in a tissue is made good through the symmetrical mitosis of similar viable stem cells, stimulated by M.c.p.s. Suppression of M.c.p. production should therefore arrest the replacement process. If this reasoning is correct, allogeneic transplantation presents some very formidable problems indeed. P. R. J. BURCH. The General Infirmary at Leeds. The Robert Jones and Agnes Hunt
Orthopaedic Hospital, Oswestry.
R. G. BURWELL. Demonstration of method of cutting domed skin-grafts.
MASKING OF ANTIGENS ON TROPHOBLAST SIR,-The objection to our paper (April 1, p. 708) raised by Dr. Fikrig and his colleagues last week (p. 1055) is valid only if it can be demonstrated that allogeneic inhibition is not
dependent upon histocompatibility differences. The cytotoxic effects of allogeneic non-immune lymphocytes on target cells and their absence with syngeneic cells are well documented6 and were demonstrated by us using human trophoblast. We are aware that many of the original transplantation immunologists are not entirely happy about this mechanism. Its existence is not disputed-only its significance. Allogeneic inhibition is, at face value, a mechanism of profound importance in the biology of cellular interactions and this is not 5. 6.
Jerne, N. K. Proc. natn. Acad. Sci. U.S.A. 1955, 41, 849. Moller, G., Beckman, V., Lundgren, G. Nature, Lond. 1966. 212,
1203.
thin steel plate (the prototype was a tobacco-tin lid) through which the anaesthetised skin is made to protrude by pressure, as shown in this demonstration (non-operative) photograph. The end of the recipient finger is pared down slightly so that it hasa split-skin circumference and the graft is attached by four or five stitches. Nineteen out of twenty-one of these grafts took well, and gave a fingertip of good quality with return of sensation and a degree of suppleness even over bone, which is sometimes not achieved by split skin itself. London N.W.I. JOHN FERGUSON. Bach, F. H., Voynow, N. K. Science, N.Y. 1966, 153, 545. Goldsmith, K. L. G. Br. med. Bull. 1965, 21, 162. Johnson, G. J., Russell, P. S. Nature, Lond. 1965, 208, 343. 8. Gasic, G., Baydake, T. Biological Interactions in Normal and Neoplastic Growth; p. 703. London, 1966. 9. Currie, G. A. Unpublished. 7.
synthesised by mast cells.) In the homograft situation, many of the T.C.F.s of the allogeneic graft will usually be complementary to host T.C.F.s and M.c.p.s. Combination between graft and host T.C.F.s will produce an accelerated discharge of host M.c.p.s, complementary to the cellular T.C.F.S of the graft. If the graft includes tissues that are normally under the control of humoral and
diminished by regarding it as non-immunological. It is not enough to suggest that lymphocytes recognise and destroy allogeneic cells by virtue of characteristics which are distinct from histocompatibility differences-a plausible alternative is
required. The failure of Dr. Fikrig and his colleagues to demonstrate lymphocyte blastogenesis due to trophoblast may well be yet another instance of the unreliability of the mixed-lymphocyteculture technique.Although no technical details were given, it is possible that lysis of trophoblast would release intracellular acidic mucopolysaccharides into the medium. These are known to coat cells in vitroand to inhibit blastogenesis in mixed lymphocyte cultures at very low concentrations.In any case, the cytotoxic effects of non-immune lymphocytes do not appear to be dependent upon blastic transformation in the allogeneic inhibition system. The effects are still present when the lymphocytes have been heavily irradiated.6 We suggest that an adequate discussion of this problem will only be possible when the experimental methods of Dr, Fikrig’s group, and ours, have been published. Edgar and Tenovus Laboratories, Charing Cross Group of Hospitals, Fulham
Hospital,
London W.6.
G. A. CURRIE K. D. BAGSHAWE.
SKIN-GRAFTING OF FINGERTIP INJURIES SIR,-I was interested to read Dr. Salaman’s paper (April 1, p. 705) and glad to see that you accorded it an annotation, for the subject is of particular interest and importance to all who work in casualty departments. Might I with all humility suggest a solution to the dilemma of split versus full thickness skin-grafts for these injuries, which is, like many British answers to
surgical problems, a compromise ? cutting domed grafts which were almost centre and split at the periphery, using a
In 1942 I started full thickness at the
cellular M.c.p.s, then both humoral and cellular factors will be involved in graft rejection. Damaged graft T.c.F.s should also combine with host immunoglobulins,2 and hence graft rejection will be accompanied by a classical (immunoglobulin) immune reaction. It follows that, if the host-versus-graft response can be adequately suppressed, then the graft should eventually fail not through immune rejection but through the loss of -cells. Normally, the stem-cell loss in a tissue is made good through the symmetrical mitosis of similar viable stem cells, stimulated by M.c.p.s. Suppression of M.c.p. production should therefore arrest the replacement process. If this reasoning is correct, allogeneic transplantation presents some very formidable problems indeed. P. R. J. BURCH. The General Infirmary at Leeds. The Robert Jones and Agnes Hunt
Orthopaedic Hospital, Oswestry.
R. G. BURWELL. Demonstration of method of cutting domed skin-grafts.
MASKING OF ANTIGENS ON TROPHOBLAST SIR,-The objection to our paper (April 1, p. 708) raised by Dr. Fikrig and his colleagues last week (p. 1055) is valid only if it can be demonstrated that allogeneic inhibition is not
dependent upon histocompatibility differences. The cytotoxic effects of allogeneic non-immune lymphocytes on target cells and their absence with syngeneic cells are well documented6 and were demonstrated by us using human trophoblast. We are aware that many of the original transplantation immunologists are not entirely happy about this mechanism. Its existence is not disputed-only its significance. Allogeneic inhibition is, at face value, a mechanism of profound importance in the biology of cellular interactions and this is not 5. 6.
Jerne, N. K. Proc. natn. Acad. Sci. U.S.A. 1955, 41, 849. Moller, G., Beckman, V., Lundgren, G. Nature, Lond. 1966. 212,
1203.
thin steel plate (the prototype was a tobacco-tin lid) through which the anaesthetised skin is made to protrude by pressure, as shown in this demonstration (non-operative) photograph. The end of the recipient finger is pared down slightly so that it hasa split-skin circumference and the graft is attached by four or five stitches. Nineteen out of twenty-one of these grafts took well, and gave a fingertip of good quality with return of sensation and a degree of suppleness even over bone, which is sometimes not achieved by split skin itself. London N.W.I. JOHN FERGUSON. Bach, F. H., Voynow, N. K. Science, N.Y. 1966, 153, 545. Goldsmith, K. L. G. Br. med. Bull. 1965, 21, 162. Johnson, G. J., Russell, P. S. Nature, Lond. 1965, 208, 343. 8. Gasic, G., Baydake, T. Biological Interactions in Normal and Neoplastic Growth; p. 703. London, 1966. 9. Currie, G. A. Unpublished. 7.