One of the obvious ways of testing the clonal selection hypothesis is to determine the minimum number of cells needed to initiate a measurable immune response. At least in the uncompromising, and now classical, hypothesis of one antigen-sensitive cell clone per antibody specificity (1, 2) it is mandatory that a given antigenic determinant should not be recognizable by every small lymphocyte--accepting that antigen-sensitive ceils are to be found among this, in several ways, heterogenous cell population. While this extreme result, if found, would truly invalidate the hypothesis it is unfortunately not possible to define exactly the maximum frequency of antigen-sensitive cells which would still be compatible with the hypothesis. Clearly, the more complex the immunological universe is thought to be, the higher becomes the number of different clones required by the hypothesis, and the lower becomes the expected frequency of a cell belonging to one particular clone. Few immunologists would probably expect a frequency higher than 10 -4.For reasons which were suggested by earlier studies of the factor of immunization (3), the strong histocompatibility antigens were considered to provide a particularly exacting test of the clonal selection hypothesis. The graftvs.-host (GVH) reactions in chicken embryos injected intravenously with adult chicken lymphocytes were used in the present study to determine the frequency of antigen-sensitive cells with re3pect to the strong antigens of the B locus (4). It is concluded that their frequency is too high to be compatible with the orthodox version of clonal selection.
Hydatid disease of bone is rare. Ivanissevich (1934) gave an incidence of 2 per cent of all forms of hydatid disease in South America, but in Australasia it is less than I per cent. Ninety new patients with hydatid disease are admitted to New Zealand hospitals every year and the death rate from it in New Zealand is &23 per million. This is twenty times as great as that in the United Kingdom, and is attributable to the remarkable disproportion between the human population (two million) and the sheep population (forty-seven million). Forty-three cases of hydatid disease of bone are recorded in the Louis Barnett Hydatid Registry
967 968 PRIMARY IMMUNE RESPONSE IN GRAFTED CELLS Materials and MethodsAnimals.--Outbred eggs (preliminary experiments) were a cross between closed flocks of Rhode Island Red and Light Sussex (purchased from the Appleby Farm Ltd., Ashford, Kent, England). Highly inbred lines of White Leghorns, I and W, were maintained by Dr. D. G. Gilmour at the School of Agriculture, University of Cambridge, from where we obtained birds for production of F1 hybrid embryos. Fertility was low, hence we were much restricted in supply of this material. Through the courtesy of Thornbers Ltd., Halifax, Yorkshire, England, ample supplies became later available of birds and eggs which were of known genotype with respect to the powerful histocompatibility and blood group locus B (5-8).Chromosome Preparations.--Colcemid-treatedsplenic ceilsweresuspendedin 0.95% sodium citrate and kept at 37°C for 20 rain. After slow spinning they were transferred to ethyl-acetic fixative (ethanol 3, glacial acetic acid 1) for ~ hr and spun again and transferred to methylacetic fixative (methanol 3, glacial acetic acid 1). The cells were then cold spread on to clean microscope slides and stained with 2% propionic orcein. Permanent preparations were made. This technique has given uniformly good preparations and the male cells of ZZ chromosome constitution were readily distinguished from female ceils which have only one large Z mediocentric chromosome.
Two rat sarcomas (CC5 and P7) which grow progressively on transplantation into normal syngeneic hosts failed to develop when injected in admixture with the Glaxo strain of Bacillus Calmette-Guérin (BCG). Under comparable conditions, the local development of a third neoplasm (P8) was temporarily inhibited and the number of pulmonary metastases significantly reduced. Experiments were undertaken to determine the extent to which the anti-tumor action of BCG required an immunocompetent host. Rats were immunosuppressed by sub-lethal whole-body irradiation (450 R), with or without prior thymectomy and challenged with inocula of mixed BCG and tumour cells when their capacity to respond to bacterial, tumour and unrelated antigens was maximally depressed. In non-sensitized immunosuppressed rats, the ability of BCG to limit tumour outgrowth was abrogated only in the case of sarcoma CC5. For this neoplasm, immunogenic in syngeneic hosts by conventional criteria, there was a statistically significant difference in the number of tumours in immunosuppressed rats (51%) compared with non-sensitized immunocompetent controls (6%). Presensitization to either bacterial or tumour antigens, prior to thymectomy and/or irradiation, fully restored the tumour-inhibitory capacity of BCG. By contrast, sarcoma P7 was not significantly less susceptible to BCG-induced regression in non-sensitized immunosuppressed rats than in nonsensitized normal rats; and sarcoma P8 similarly failed to reveal any significant differences in susceptibility to BCG affecting primary or secondary tumour development. It is concluded that tumours may vary widely in their sensitivity to host reactions aroused by BCG. Certain neoplasms, exemplified by sarcoma CC5, require participation of an immune reaction of delayed hypersensitivity type for optimal destruction at BCG sites, while for others (e.g. sarcoma P7) an immunoreactive component of this type is not essential. By contrast, a third category of tumour (e.g. sarcoma P8) is relatively resistant to host reactions induced by the mycobacteria. An important component of BCG-mediated tumour inhibition is not dependent on an immunologically intact host.
1. Certain macroscopical and microscopical features of the tendo calcaneus of the rabbit are described and illustrated, and the vascularisation as revealed by Spalteholz clearing is presented. 2. The vessels of the epitenon are chiefly derived from proximal and distal sources. 3. The vessels of the paratenon are derived from the main arteries of the leg. 4. The two vascular systems are largely independent of each other except along one edge of the tendon by way of a mesotenon. 5. The paratenon, epitenon and mesotenon and the related vessels are comparable to those found in tendons with synovial sheaths. By inference and from evidence obtained by dissection on the living human subject it is suggested that the arrangements are similar in the human tendo calcaneus. 6. Considerable friction develops on movement between the surfaces of the paratenon and epitenon. This might be significant in pathological states of the human tendon.
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