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Biomedical subjects

P McCullagh

Publications and source records attributed to P McCullagh.

At least 73 records · Page 4Linked to original sources
PubMed1982

The response of the pregnant ewe to challenge with foetal and paternal lymphocytes.

The efferent lymph from the popliteal lymph nodes of pregnant ewes challenged between 93 and 127 days with specific paternal or foetal lymphocytes was examined. There was an increased efflux of lymphocytes and blast cells from the challenged node, similar to that observed during the response of normal, non-pregnant ewes to allogeneic cells. Additionally, there was a decrease in the mixed lymphocyte and mitogen responsiveness of the efferent lymphatic cells that was comparable with that evoked by challenge of non-pregnant sheep. While cytotoxic cells could not be detected in the lymph after challenge of normal or pregnant animals, specific cytotoxic antibody was invariably produced in both instances. The present observations that the immune responsiveness of the pregnant ewe to foetal lymphocytes remains normal are consistent with an earlier report on the antifoetal reactivity of maternal cells in vitro. It is inferred that the in vitro reactivity of maternal lymphocytes was a valid reflection of the capacity of these cells in the intact ewe.

Animals↗
PubMed1982

The response of the foetal lamb to maternal lymphocytes.

Foetal lambs were inoculated with either maternal or third-party lymphocytes. Of foetuses transfused in the first half of pregnancy (from 49 to 73 days), one quarter survived until the fifth month. Examination of the immunological reactivity of these survivors revealed that all rejected skin grafts from the lymphocyte donors and manifested normal mixed lymphocyte reactivity. In two instances, responsiveness of the transfused lambs to normal lymphocyte transfer was reduced. Foetal lambs transfused with large numbers of maternal lymphocytes in the last third of pregnancy could survive provided the donor ewe had not been sensitized against foetal or paternal determinants. Following intravenous challenge with maternal lymphocytes, cells collected over a prolonged period from the thoracic duct of the foetal recipient exhibited depression of anti-maternal reactivity in mixed lymphocyte culture.

Animals↗
PubMed1982

Some aspects of analysis of covariance.

An account from first principles is given of a number of aspects of analysis of covariance. Six different meanings of analysis of covariance are outlined and the history of this technique is sketched briefly. The development of the key formulae from the method of least squares is described, and generalizations to other distributions in the exponential family are mentioned. Special problems of application in randomized experiments and in observational studies are discussed. Finally, the decomposition of regression relations is considered along with components of covariance.

Analysis of Variance↗
PubMed1981

Immunological responsiveness of maternal and foetal lymphocytes during normal pregnancy in the ewe.

Peripheral blood lymphocytes collected from ewes before and during pregnancy manifested constant reactivity to concanavalin A and to paternal and third party peripheral blood lymphocytes. However, in some instances, the reactivity of these maternal cells against lipopolysaccharide and lymphatic lymphocytes from paternal, foetal and third-party donors increased markedly during pregnancy. Apart from an indication that plasma from some pregnant ewes acquired the capacity to depress lymphocyte reactivity non-specifically, no evidence was obtained to suggest that maternal lymphocyte reactivity observed in vitro did not accurately reflect the capacity of these cells in the donor ewe. In particular, there was no indication that populations of maternal peripheral blood lymphocytes returning from the gravid uterus had undergone any modification of reactivity against foetal determinants.

Animals↗
PubMed1981

Immunological reactivity of maternal lymphocytes during normal pregnancy in the rat.

Thoracic duct lymphocytes from pregnant PVG rats differed markedly from similar cells collected from non-pregnant donors in their reactivity in popliteal lymph node assays performed in (PVG x DA) F1 hybrid hosts. Cells from pregnant rats failed to evoke an increase in popliteal node size commensurate with higher challenge doses of lymphocytes. This modification in maternal lymphocyte reactivity was not dependent on the presence of foetuses genetically compatible with the F1 hybrid rats used in the popliteal lymph node assay. The mechanism responsible for the decrease in size of responding F1 hybrid popliteal lymph nodes appeared to be based on a reduced capacity of lymphocytes from pregnant donors to stimulate a response by host lymphocytes.

Animals↗
PubMed1981

Specific inhibition of anti-self reactivity following exposure of neonatal rats to lymphocytes with anti-neural activity.

Not only did newborn rats prove to be resistant to the adoptive transfer of responses against central nervous system tissues following the injection of lymphocytes from rats sensitized against syngeneic spinal cord, but such recipients were also subsequently resistant as adults to the active induction of an immune response following challenge with syngeneic cord. This resistance to active immunization against syngeneic spinal cord as adults was associated with the absence of lymphocytes with anti-neural activity and with the appearance of cells able to suppress such activity, after challenge. Interference by the lymphocytes of resistant rats with anti-neural responses was restricted to those responses directed against syngeneic neural cells.

Animals↗
PubMed1981

Migration of lymphocytes sensitized against syngeneic and allogeneic spinal cord after infusion into susceptible and resistant syngeneic and semi-allogeneic hosts.

Lymphocytes from rats that had been sensitized against spinal cord were infused into unsensitized hosts, and the ability of cells subsequently recovered from the thoracic duct lymph of these recipients to mount anti-neural responses was tested. Lymph from normal recipients frequently contained reactive lymphocytes during the 4 days following infusion of sensitized cells, whereas cells that had been recovered from transfused rats, resistant to encephalomyelitis as a result of neonatal treatment, were almost invariably benefit of activity. If lymphocytes reactive against allogeneic neural cells were passaged through F1 hybrids of the lymphocyte and sensitizing allogeneic tissue strains, loss or retention of their ability to attack allogeneic neural cells was determined by the method of sensitization of the original lymphocyte donor.

Animals↗
PubMed1981

Reactivity of neuro-antigen-sensitized lymphocytes against syngeneic, allogeneic and tolerated allogeneic neural tissue.

Lymphocytes reactive against cultured cerebellar cells were collected from rats that had been sensitized against a variety of preparations. While cells with in vitro reactivity were invariably present in lymph from rats which were to develop encephalomyelitis, the reverse did not apply. Challenge with either neural or non-neural allogeneic tissue sensitized effectively against allogeneic neural tissue. Challenge of homograft-tolerant rats with either syngeneic or tolerated allogeneic spinal cord sensitized against neural tissues of tolerated strain.

Animals↗
PubMed1980

Recognition of histocompatibility determinants controls reactivity of auto-sensitized lymphocytes against neural tissues.

Thoracic duct lymphocytes from rats sensitized against syngeneic spinal cord rapidly produce damage in cultures of syngeneic cerebellar cells but coexist indefintely with allogeneic cultures. Lymphocytes from donors that have been sensitized against allogeneic spinal cord attack cultures of syngeneic and specific allogeneic cerebellum but not cells from rats of a third, unrelated strain.

Animals↗
PubMed1980

Immunological reactivity between chimeric cattle twins. I. Homograft reaction.

The response of chimeric calves to grafts of cotwin skin was examined both by direct observation of the fate of the graft and by collection of lymph from the lymph node which drained the grafted area. Whilst grafts of body skin exchanged between 16 pairs of twins survived for longer periods than did grafts transferred between unrelated calves, all of the former had been rejected after 10 weeks. Secondary grafts of cotwin body skin were rejected significantly faster. In contrast, grafts of auricular skin exchanged between cotwins survived indefinitely in some instances despite the rejection of simultaneously transferred body skin. The magnitude of the blast cell response observed in efferent lymph in the case of grafts exchanged between cotwins was generally intermediate between that observed in responses to allografts and control autografts. However, an early peak of blast cell response which occurred some 50 hr after placement of allogeneic grafts was not observed in response to cotwin grafts.

Animals↗
PubMed1980

Immunological reactivity between chimeric cattle twins. II. Normal lymphocyte transfer.

The response of normal single-born calves to the s.c. injection of allogeneic lymphocytes and that of chimeric calves to allogeneic and cotwin cells were studied. Whereas allogeneic cells produced local dermal swelling along with an efflux of blast cells and specific cytolytic antibody in the regional lymph, the injection of cotwin lymphocytes into chimeric calves failed to produce responses in excess of those of controls. There was little indication of specific reduction in responsiveness of the lymphocytes of normal calves following challenge with allogeneic cells.

Animals↗
PubMed1980

Immunological reactivity between chimeric cattle twins. III. Mixed leukocyte reaction.

Leukocytes from chimeric calves invariably failed to mount a proliferative response in excess of control responses when cultured with cotwin cells as stimulators. The levels of cellular proliferation in control cultures of leukocytes from chimeric donors were so low as to exclude the occurrence of any auto-stimulation, and it was clear that the absence of excess proliferation in mixed cultures could not be attributed to elevated background levels. Attempts to restore reactivity in mixed leukocyte culture by removal of cell subpopulations from chimeric calf leukocytes and by modification of cell surfaces were unsuccessful. It was inferred that the unreactivity between chimeric cotwins manifest in the normal lymphocyte transfer and mixed leukocyte reactions was unlikely to be produced by humoral or cellular blocking mechanisms.

Animals↗
PubMed1980

The relevance for the immunological responsiveness of an animal of selective entry to and egress from the lymph of antigenically reactive cells.

Although various forms of antigenic challenge of an animal can be shown to modify the capacity of its circulating lymphocytes to respond to the same antigen after re-exposure, the underlying mechanisms have not been elucidated. Of two groups of experiments concerned with the induction of unresponsiveness in circulating lymphocytes, those instances in which unresponsiveness has been produced in the circulating lymphocyte population of rodents challenged with conventional antigens have been claimed to reflect the sequestration of specifically reactive cells in fixed lymphoid tissues. Two observations with which the explanation is incompatible are that unreactive populations can be reactivated readily following their removal from the antigenically challenged animal and that apparently unreactive cells can modify the reactivity of normal populations of lymphocytes when they are transferred together to irradiated hosts. It is not difficult to demonstrate that plasma from rats recently challenged with antigen contains humoral factors able to interfere non-specifically with the reactivity of normal lymphocytes, and the possibility that similar influences may contributed to lymphocyte unresponsiveness after antigenic challenge cannot be dismissed. A second group of experiments, which have been interpreted as an example of selective removal of specifically reactive cells from the circulation, concern the loss of reactivity by parental strain lymphocytes which have been passaged through F1 hybrid hosts. In this situation it can be shown that not only have specifically reactive cells accumulated in the spleen, but also that the retained cells have been subject to a reversible inactivation. Consequently it is probable that the unreactivity of the passaged parental strain lymphocytes in these experiments results from a mechanism quite different from that responsible for the unreactivity of circulating lymphocytes observed in animals challenged with conventional antigens.

Animals↗
PubMed1978

Influence of secondary inoculum of tumour cells on growth of primary tumour.

The effect of successive inocula of tumour cells given to rats at intervals of 1 to 10 days was examined. If W256 cells were injected on both occasions, the second inoculum failed to grow if given into the footpad as early as 1 day, or intravenously as soon as 4 days, after the first administration. However, although a second inoculum failed to grow, it produced significant augmentation of the growth of the primary implant if given during its latent or growth phases. If the second inoculum contained cells from a fibrosarcoma unrelated to W256, its growth was effectively curtailed if the initial inoculum had preceded it by 24 h or more. However, secondary inocula of fibrosarcoma cells did not augment the growth of the primary W256 tumour.

Animals↗
PubMed1977

Transplacental influence of the thymus.

Peripheral blood lymphocyte levels attained in adult rats that had been thymectomized at birth were markedly reduced if the two or three immediately preceding generations of rats from which they were bred had been thymectomized as neonates. The capacity of thymectomized animals to survive to adult life was also drastically reduced if they were bred from thymectomized stock. Pregnancy as a result of mating with syngeneic or allogeneic males produced an ephemeral increase in peripheral blood lymphocyte levels of third and fourth generation thymectomized females. These observations are most readily explicable on the basis of a thymus-derived humoral influence acting directly or indirectly to influence the circulating lymphocyte population.

Animals↗
PubMed1977

Anti-parental lymphocyte reactions in neonatal F1 hybrid rats.

The subpopulation of parental-strain lymphocytes responsible for the recognition of a particular F1 hybrid strain as foreign has been shown to be subject to specific, reversible inactivation after its injection into neonatal rats of that F1 hybrid strain. Neonates born to mothers that were syngeneic with the parental-strain lymphocytes under test acquired the capacity to inactivate these lymphocytes at an earlier age than did the genotypically identical reciprocal F1 hybrids. Neonates had little capacity to inactivate completely allogeneic lymphocytes. It is inferred from the difference in behavior between reciprocal F1 hybrids that the augmented ability to inactivate anti-F1 hybrid maternal-strain lymphocytes follows exposure to such cells in utero and to antibodies with anti-F1 hybrid activity in colostrum. Specific inactivation of those marauding maternal lymphocytes with anti-fetal activity is envisaged as an important means of protection of the fetus from immunological attack by the mother. On the basis of the results presented in this and the preceding paper, it has been proposed that many of the sequelae of the transfer of immunocompetent parental-strain cells to F1 hybrid animals result not from graft anti-host activity but from an F1 hybrid anti-parental lymphocyte response that has eluded normal regulatory mechanisms. These experiments also raise the possibility that regulation of auto-immune responses may be achieved by the inactivation of lymphocytes with anti-self reactivity by other lymphocytes that respond to the recognition structure required for such reactivity.

Animals↗