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Biomedical subjects

R E Billingham

Publications and source records attributed to R E Billingham.

At least 73 records · Page 4Linked to original sources
PubMed1976

In vitro studies on the T-lymphocyte population of human milk.

Human milk lymphocytes (ML) can be partially purified and propagated in vitro as a means of assessing their immunological function. When exposed to a variety of stimuli known to activate T lymphocytes, ML respond in a unique manner that indicates a selected population of immunocompetent cells. ML are hyporesponsive to to nonspecific mitogens and respond in a reduced manner to histocompatibility antigens on allogeneic cells. In most cases, they are completely unresponsive to C. albicans although blood lymphocytes from the same patients respond to the antigen. The Kl capsular antigen of E. coli induces significant proliferation in lymphocytes obtained from milk, but fails to stimulate blood lymphocytes. This dichotomy of reactivity does not appear to result from suppressive factors or cells in milk or insufficient adherent cell function. Rather it appears to reflect the accumulation of particular lymphocyte clones in the breast and the local nature of mammary tissue immunity at the T-lymphocyte level.

Antigens, Bacterial↗
PubMed1976

The feasibility of altering the immunogenicity of grafts.

Most attempts to prolong the survival of allografts have involved treatment of the host to impair its capacity to reject them. Early uncritical attempts to treat the graft rather than the host were received with skepticism because of the prevailing belief that the alloantigens on cell surfaces are immutable. However, over the past decade unequivocal evidence has accumulated that the immunogenicity of allografts is susceptible to alteration. Short-term maintenance in vitro of malignant and normal tissue grafts, such as those of the ovary and thyroid. Weakens their susceptibility to rejection. Various agents have been identified which, when applied to tissues or organs in vitro, have a similar effect. Soaking skin in media containing steroids, urethane, thalidomide, antilymphocyte globulin (ALG), and specific alloantibody is also effective. X-irradiation and perfusion of allogeneic dog kidneys with solutions of concanavalin A or of nucleic acid prepared from the future donor or even from indifferent donors or microoorganisms lead to extended survival. There is also equivocal evidence that soaking mouse skin grafts in RNA prepared from unrelated donors causes them to be treated as allogeneic by syngeneic recipients. Skin from animals suffering from certain diseases displays altered immunogenicity. Skin from mice suffering from virus-induced leukemia or lymphocytic choriomeningitis is frequently rejected by syngeneic recipients. By contrast, skin allografts from some cancer patients and from mice bearing certain tumors give evidence of prolonged survival as do grafts from uremic mice. Some treatments of prospective donors, including cytotoxic drugs, ALG, specific alloantisera, hypoxia, and experimentally produced uremia, also extend the lives of allografts. Trophoblast, a fetal epithelial tissue in immediate contact with maternal tissue, represents a natural example of graft adaptation. Despite its origin from precursor cells with normal transplantation properties, trophoblast fails to elicit transplantation immunity and is unaffected by it. Some of the disparate agents or procedures described here probably act by modifying grafts in such a way that they are more likely to evoke "blocking" or enhancing antibodies rather than the usual destructive cellular immunity, and many of them deplete the grafts of immunogenically effective "passenger" leukocytes. Both of these processes contribute to apparent hypoantigenicity.

Adrenal Cortex Hormones↗
PubMed1975

Histoincompatibility and maternal immunological status as determinants of fetoplacental weight and litter size in rodents.

Studies conducted upon inbred strains of mice, hamsters and rats have shown that following the interstrain matings the now familiar covert reactivity of pregnant females to the alloantigens of their conceptuses may benefit the latter in two ways; firstly, it exerts a significant influence upon placental weight, and indirectly upon the birth weight of the fetus-allogeneic placentas tending to be heavier than syngeneic placentas, and mothers specifically presensitized against alien paternal tissue antigens gestate fetuses with heavier placentas than normal females. Specifically tolerant mothers, on the other hand, produce smaller, F1 hybrid, fetoplacental (fp) units. The classic notion that the disparity between the birth weights of F1 hybrid and homozygous offspring is due to hybrid vigor has been challenged by the finding that DA and (DA times F1)F1 hybrid blastocysts transferred to the uteri of genetically tolerant (DA times F1)F1 hybrid rats produce fp units of similar weight Maternal immunological reactivity against the fetus qua allograft may make a significant contribution here. Additional support for the premise that maternal reactivity against fetal alloantigens in some way promotes the growth of the fp unit was afforded by the finding that excision of the para-aortic lymph nodes (which drain the uterine horns) from females before interstrain matings resulted in smaller fp units than in females subjected to sham operations. The finding with one rat strain combination that passive immunization of females with serum against their F1 hybrid conceptuses promoted the growth of the latter suggests that a humoral rather than a cellular immunity may be involved. Secondly, in the three species studied, it was observed that genetic disparity between a conceptus and its mother significantly improved its chances of implantation and development to term.

Animals↗
PubMed1975

Immunologic benefits and hazards of milk in maternal-perinatal relationship.

Aside from nutritional significance, milk affords infant mammals immunologic benefits. However, it is not without immunologically based hazards. These stem from its antigenicity and the fact that in certain species that receive their maternal immunologic endowment postpartum, hemolytic disease of the newborn may be mediated by colostral antibodies. Awareness that viable leukocytes are ingredients of colostrum and milk has stimulated interest in the significance of these cells. Skin grafting tests on foster-nursed rats and mice have given circumstantial evidence that, in these species, leukocytes may be transmitted naturally from the mother's blood stream to the suckling's blood stream through the milk, and that these cells may be beneficial (adoptive immunization) or, in some genetic contexts, harmful (initiating graft-versus-host disease). In man, too, studies on necrotizing enteritis and other disease provide increasing support for the thesis that leukocytes in milk fulfill a protective function, possibly as a consequence of their "natural" transplantation.

Animals↗
PubMed1973

Skeletal muscle as a privileged site for orthotopic skin allografts.

A semi-privileged status for rat skin allografts may be achieved by placing them on extensive open beds formed by panniculus carnosus muscle which prevents contact of the transplant with host skin. Such allografts enjoy approximately a twofold increase in their life expectancy, even if transplanted across a strong histocompatibility barrier. Experiments are described which rule out stress or a "central" weakening of response, such as enhancement, as explanations of this phenomenon. Intact skin "islands" separated from surrounding host skin on all sides by a broad border of bared panniculus were also found to serve as privileged sites. Dye injected into these islands failed to reach the regional nodes until about the 15th day after their preparation. These studies indicate that a lymphatic deficit is responsible for the observed privileged status of the allografts.

Animals↗