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Biomedical subjects

R E Billingham

Publications and source records attributed to R E Billingham.

At least 37 records · Page 2Linked to original sources
PubMed1986

Concerning the immunology of the uterus.

As a mucosal organ, the uterus is unique in being subject to exposure to three types of antigen: chronically to micro-organisms, episodically to sperm bearing both auto- and alloantigens as well as soluble antigens in seminal plasma, and to conceptuses--nature's allografts--expressing transplantation antigens. That the uterus is effective in handling pathogens is evidenced by the rarity of infections. Local macrophages, immunocytes, and a secretory immune system, most evident in the cervix, probably underlie this attribute. Mammals' reproductive success hints that the uterus is immunologically discriminating toward the nonharmful but biologically important antigens of classes 2 and 3. Why sperm are not normally destroyed immunologically in the female prior to fertilization and why conceptuses are not rejected are central unresolved questions in reproductive immunology. Undoubtedly, important immunoregulatory principles are operating in this remarkable organ and its decidua. Better to understand antigenic exposure in the rat uterus, we have reinvestigated its lymphatic drainage using labeled cell injection and microanatomical procedures. Despite abundant lymphatics in the myometrium, cells placed in the uterine lumen did not readily gain access to the lymphatic system. There was a paucity of lymphatics in the endometrium, but Ia-positive dendritic cells were abundant. Soluble antigen exposure via the uterus failed to evoke a primary antibody response yet did prime the host for a secondary response. This restriction of systemic antigen presentation from the uterus, in conjunction with both cellular and noncellular immunoregulatory principles acting locally, may be important to ensure maternal hyporesponsiveness to paternal alloantigens.

Animals↗
PubMed1986

Recipient treatment to overcome the allograft reaction, with special reference to nature's own solution.

The 6th decade of this century was particularly important for transplantation immunology. The universality of allograft rejection by normal hosts had won general acceptance and, experimentally, several means of abrogating host reactivity to allografts were discovered. These included sub-lethal whole body irradiation, administration of certain corticosteroid hormones and inoculation of very young animals with living cellular inocula from the future graft donor--i.e., classic, neonatal tolerance. The latter was particularly important since it indicated the feasibility of a specific, permanent solution to the clinical allograft problem. Radiation and drug-induced tolerance in adult subjects came along and chemical immunosuppressants, which led to successful clinical use of azathioprine. The important rediscovery of ALS pointed towards the development and clinical application of monoclonal antibodies many years later. With the development of immunogenetics and transplantation biology came recognition that the conceptus is a highly successful allograft, raising the question of how it is able to withstand rejection by its immunocompetent mother for the duration of pregnancy. Hopefully, knowledge of the principle(s) involved when they are finally elucidated will be applicable to clinical allograft recipients. Although functional hypoantigenicity of the syncytial trophoblast probably plays a major role in protecting the allogeneic conceptus, a strong case now exists that local, cell-based, immunosuppressive and immunoprotective activity within the placenta and decidua, mediated by suppressor and other cells, is important.

Animals↗
PubMed1985

Premarital contraceptive use: a discriminant analysis approach.

The ability of seven independent variables to predict accurately, from a sample of unmarried, sexually active students, which ones use reliable contraceptives and which ones use unreliable contraceptives, was investigated. Using discriminant analysis, the seven independent variables were age individuals started engaging in coitus, frequency of coitus, frequency of dating, length of time sex partners knew each other, number of sex partners, having anticipated coitus to occur, and the number of close friends who were thought to use birth control. The results indicated that these variables were accurate in predicting which students were users of contraceptives, with more than 80% of males and females being correctly classified. The number of close friends thought to use contraceptives was the most influential variable for both sexes, followed by length of time the partners knew each other.

Adult↗
PubMed1985

Maternal--fetal immune interactions and the maintenance of major histocompatibility complex polymorphism in the rat.

In several different strain combinations of rats, an R2 backcross was used to assess the relative fitness of progeny MHC-incompatible with their mothers as compared to that of MHC-compatible progeny. None of the various treatments used to alter maternal immunoregulatory processes, namely splenectomy, active or adoptive immunization, or the induction of transplantation tolerance, was able to perturb consistently the population distribution of RT1 antigens. Though the extreme variability of RT1 heterozygote excess remains poorly understood, studies of parity-associated changes in the population distribution of RT1 heterozygotes: RT1 homozygotes nonetheless do support the hypothesis that the spleen is important to the immunoregulatory control of these phenomena.

Animals↗
PubMed1985

Immune privilege in the testis. II. Evaluation of potential local factors.

The significance of several local factors in prolonging allograft survival in the rat testis has been investigated. The lower temperature of this organ was shown to have no effect, because parathyroid gland allografts implanted s.c. in the ear, which is similarly hypothermic, were rejected as promptly as in conventional sites. Conversely, testes secured in the abdominal cavity afforded privilege to grafts just as well as normal testes. With indirect immunofluorescence using a monoclonal antibody, it was shown that the testis' interstitial tissue is well-endowed with cells bearing class II histocompatibility antigens, a prerequisite for antigen-processing capability. When intratesticular allograft recipients were pretreated with estrogen to suppress Leydig cell synthesis of testosterone, most grafts were rejected promptly, suggesting that local steroid secretion is important in testicular immune privilege. Both testes and s.c. sites supported inflammatory reactions to cotton pledgets, indicating that there is no interference with the nonspecific inflammatory process necessary for graft rejection, but more likely with antigen processing itself.

Animals↗
PubMed1984

H-Y antigen and immunity: a means for controlling the secondary sex ratio?

C57BL/6J female mice were splenectomized and then sensitized to the H-Y antigen by means of grafts of H-Y incompatible skin and injections of spleen cells from syngeneic males. When subsequently mated to syngeneic males the secondary sex ratio of progeny born was significantly greater than that of controls. However, the effect was manifest only among the progeny of later litters (i.e., 3, 4, 5) suggesting that repeated exposure to the H-Y antigen during the course of pregnancy was essential to bring about demonstrable immunoregulatory changes.

Animals↗
PubMed1983

Reconsideration of the lymphatic drainage of the rat testis.

An extensive investigation of the lymphatic drainage from the rat testis was carried out in an effort to detect any characteristics which might be important in the immunological privilege the testis extends to allografts. Three different methods revealed a consistent and very efficient lymphatic drainage involving primarily the iliac and renal lymph nodes and to a lesser extent the external lumbar, para-aortic, and posterior gastric nodes. Within minutes, dye or labeled cells injected into the testis could be found within regional nodes. Node hypertrophy was induced by injecting the testes of F1 hybrids with parental strain lymphoid cells (a regional graft-versus-host reaction). Besides indicating that efficient filtration occurs in these nodes, this also established that they are a hospitable environment for cellular immune reactions. Similarly, the capacity of allogeneic cells injected into the testis to induce production of humoral alloantibodies by recipients confirms that exposure to antigens via this route does not in itself suppress immune responsiveness.

Animals↗
PubMed1983

Immune privilege in the testis. I. Basic parameters of allograft survival.

The fate of solid tissue allografts--skin or parathyroid glands--implanted in the interstitial tissue of the testis was investigated using inbred rats. The results affirm that the testis is an immunologically privileged site despite its efficient lymphatic drainage. Skin allografts survived at least several days longer than orthotopic grafts of similar size, whether major histocompatibility complex (MHC)-compatible or MHC-incompatible, and failed to induce an alloantibody response in most recipients or to prime for secondary antibody responses on rechallenge. Further assessment employed parathyroid grafts that allowed appraisal of their function and its duration, by monitoring serum calcium levels. Most intratesticular MHC-incompatible parathyroids survived for at least twice as long as control grafts in nonprivileged sites, with a median survival time (MST) of 41 days--and one-third of the grafts functioned at 100 days. MHC-compatible grafts fared even better (MST of 60 days), some surviving more than 400 days. Most F1 hybrid grafts survived virtually indefinitely. Splenectomy 5-23 days prior to implantation had a beneficial rather than a detrimental effect on the privilege afforded intratesticular parathyroid allografts. Allograft rejection was accompanied by antibody production in only one-half the animals. Grafts that had undergone functional rejection at the time of recovery usually had an intense mononuclear cell infiltrate, and long-term surviving grafts displayed varying degrees of cellular infiltration among cords of healthy, functional chief cells. Accepted parathyroids were destroyed by active immunization of the host but were unaffected by passively administered alloantibodies. The possible mechanisms controlling graft rejection in this unique privileged site are discussed.

Animals↗
PubMed1981

The H-Y antigen and its role in natural transplantation.

A concise overview of the transplantation biology of the H-Y antigen is presented with particular reference to: its prototypic behavior as a weak transplantation antigen; the facility with which mice of certain inbred strains can be rendered tolerant of H-Y incompatible skin grafts; its capacity to instigate graft-versus-host reactions; its significance in clinical transplantation; and finally, H-2 control of anti-H-Y immune responses. The role of the H-Y antigen in natural transplantation, i.e. pregnancy, is then reviewed. Evidence is presented to support the hypothesis that in certain cases maternal immune responses directed specifically to the H-Y antigen can exert selective pressures on male zygotes, producing deviant sex ratios in certain experimental and clinical situations.

Animals↗
PubMed1981

Current trends in reproductive immunology: an overview.

Over the past decade has come general recognition that, directly or indirectly, immunology intrudes into nearly every aspect of mammalian reproduction. Charles Darwin's notion that the profligacy of women led to reduced fertility gained plausibility with the subsequent discovery of the auto- and alloantigenicity of spermatozoa and of testicular material. From this observation arose the reasonable expectation that immunological control of fertility may be feasible. Discovery of the importance of natural transfer of immunity from mother to offspring, the ontogeny of the immune response, and recognition that pregnancy is an almost consistently successful violation of the "laws of transplantation' are only a few highlights or components of the burgeoning, multifaceted field we have come to recognize as the immunology of reproduction. An overview of this subject is here presented with regard to its evolutionary origins, its accomplishments, its current trends, and some of its potentialities. The immunology of reproduction has not developed in isolation; in recent years it has benefited enormously from developments in other fields, and in its turn it has exerted its own impact on other disciplines, especially on transplantation. The present preoccupation of many immunologists with immunoregulation stems largely from independent discoveries in the realm of reproductive immunobiology - the etiology of Rhesus disease and its prophylaxis, and the principle of immunological tolerance, from investigations on the peculiarities of dizygotic twins in cattle.

Antibodies↗
PubMed1981

Capacity of "transplanted" lymphocytes to traverse the intestinal epithelium of adult rats.

Suspensions of viable lymph node cells (LNCs), both unlabeled and 3H-uridine labeled, from adult Fischer (FI) rats were inoculated into the lumens of established, surgically isolated segments of ileum in adult (FI x DA)F1 hybrid hosts. Vascular, lymphatic, and nerve supplies of the isolated segment were preserved. It was reasoned that subsequent hypertrophy of the draining mesenteric LN complex, on an immunogenetically specific basis (attributable to graft-versus-host (GVH) reactivity) and histological identification of labeled lymphoid cells in the intestinal wall of the isolated segment, would be indicative of the passage of inoculated cells across the intestinal epithelium. It was found that host mesenteric LNs were significantly larger on the 8th postinoculation day in animals that received 100 x 10(6) or 300 x 10(6) FI LNCs than in animals that were given similar numbers of syngeneic F1 hybrid cells (controls). This lymph node hypertrophy was dosage dependent and favorably influenced by the presence of Peyer's patches. The results of experiments involving introduction of 3H-uridine-labeled cells into isolated ileal segments and subsequent radioautography corroborated the conclusion that lymphocytes deposited in the intestinal lumen can gain access to host tissues, i.e., they are "naturally transplanted."

Animals↗
PubMed1981

Distribution of fibronectin during wound healing in vivo.

The distribution of fibronectin during wound healing has been studied. Full thickness wounds were made in the skin on the sides of guinea pigs' trunks. Biopsy specimens were taken from the normal skin, from the 5-hr-old wound, and on days 1-18 after wounding. Unfixed frozen sections were analyzed for fibronectin distribution by indirect immunofluorescence analysis with a specific antiserum prepared in rabbits against guinea pig plasma fibronectin. Tissue samples were also embedded in methacrylate and sections cut and stained with hematoxylin and eosin for general histology or with a silver stain for reticulin. Fibronectin was prominent in the basement membranes of normal skin epidermis. It was also present in the papillary dermis and to a lesser extent in the reticular dermis. After wounding, fibronectin was part of the fibrin clot and distributed along fibrin strands. Fibronectin was also deposited along newly synthesized collagen in the granulation tissue, which was at least in part collagen type III based upon staining for reticulin. Eventually, the entire granulation tissue was transformed into aligned collagen fibrils coated with fibronectin. Throughout the period of wound healing, the level of fibronectin associated with what appeared to be type I collagen in the reticular dermis adjacent to the wound area stayed about the same. When fibrils with the histological characteristics of type I collagen were within the granulation tissue, however, they were coated with fibronectin. The results indicate that fibronectin is a major component present during wound healing.

Animals↗