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PubMed1987

Immunological and para-immunological mechanisms in spontaneous abortion: recent insights and future directions.

Unexplained spontaneous abortion in humans is currently thought to be related to genetic or immunologic factors. Animal models of spontaneous abortion have been used to try to gain some insight into the problems in humans. From studies of animal models there is increasing evidence that a variety of mechanisms may initiate pregnancy failure and participation of immunologic effectors may be a secondary event. Recent studies indicate that murine abortion that occurs spontaneously (without deliberate immunization by the investigator) may be initiated by para-immunologic host effector cells such as NK cells, macrophages and their toxins that possess selective toxicity which is not antigen-specific. The potential importance of local non-specific suppressive mechanisms in the uterus is also highlighted by their ability to block non-specific para-immune effector cell activation, and by their potential relationship to growth factors in decidual supernatants that promote placental cell growth in vitro. Levels of non-specific suppression do not appear low when fetal death can be attributed to a genetic mutation. The concept that different tissue components of the feto-placental unit serve as targets of different immunologic and para-immunologic effectors is defined. The new insights into the pathophysiology of murine abortion and its correction can provide a useful framework for further analysis of the role of para-immunologic effector mechanisms in unexplained abortion in humans and in non-murine veterinary conditions.

Abortion, Spontaneous↗
PubMed1977

Biological and immunological characterization of human luteinizing hormone: II. A comparison of the immunological and biological activities of pituitary extracts after electrofocusing using different standard preparations.

The profile of immunologically active human luteinizing hormone (hLH) was determined in aqueous pituitary extracts after electrofocusing using two radioimmunoassay systems and the estimates for each fraction were compared to those obtained by an in vitro bioassay method. Similar biological and immunological profiles were obtained in the pH 7.0-9.0 region, where most of the biological activity was present. Biological to immunological (B/I) ratios ranging from 0.6 to 1.7 (mean ratio 1.01; n = 21) were found in the major biologically active fractions of this pH region when a highly purified human pituitary LH preparation (68/40) was used as standard in both types of assays. The close proximity of these ratios to unity indicates a similar composition of biological and immunological activities in all these fractions in relation to that of the highly purified standard. However, marked discrepancies were observed in the pH region 3.0-7.0 where the B/I ratios ranged from 0.1 to 0.9, indicating the presence of immunological activity associated with relatively little biological activity. When impure human LH preparations of pituitary (69/104) and urinary (hMG 2nd IRP) origin were used as standards for the bioassay and radioimmunoassay of the hLH present in the major fractions of the pH region 7.0-9.0, significantly higher B/I ratios were obtained than with the use of the highly purified standard (68/40). These elevated B/I ratios are attributed to the presence in the impure standard preparations of immunological activity, which is associated with little or no biological activity. These observations may provide an explanation for the differences in B/I ratios which were reported for hLH in plasma, using different standard preparations.

Biological Assay↗
PubMed2006

The larynx as an immunological organ: immunological architecture in the pig as a large animal model.

The larynx is a mucosal organ positioned at the divergence of the respiratory and digestive tracts. It is exposed to a wide variety of environmental components, including foreign antigens, tobacco smoke, laryngopharyngeal reflux and pollutants. The mucosal immune system generates either active immune responses or tolerance, depending on the nature of the antigen and we hypothesize that the larynx is important organ for immunological decision-making in the airway. Because the pig is an ideal large animal model in which to explore laryngological research questions, such as those relating to laryngeal transplantation, we investigated the normal mucosal immunology of the porcine larynx. Pig larynges and tracheae were processed and prepared for bright-field microscopy and quantitative, multiple-colour immunofluorescence histology using pig-specific monoclonal antibodies. There was an abundance of immunologically active cells within the mucosa of the larynx and trachea of both the newborn and adult animal. Specifically, major histocompatibility complex class II (MHC class II+) cells, CD4+ and CD8+ cells were identified, although regional differences in numbers were apparent: specifically, the supraglottis contained fewer immunologically relevant cells than other sites sampled. There was a significant correlation between the numbers of MHC class II+ and CD4+ cells indicating co-ordinate regulation and therefore functional local interactions. The presence of such an immunological structure suggests that the larynx may have important functions in respiratory immunology and that it may trigger strong alloresponses after laryngeal transplantation.

Animals↗
PubMed1983

[Immunology - results of two decades of immunological research].

The discipline of immunology has made very rapid progress during the past twenty years. A general introductory part was followed by a discussion of immunological components in resistance. Subsequently, the importance of controlling the immunological system was stressed. The significance of the network theory was briefly referred to. Attention was then drawn to specific and non-specific stimulation of the immune response, which are essential both in theory and in actual practice. A number of instances are cited to illustrate these features in recent developments in the fields of preparation of vaccines and immunological treatment of cancer. It was pointed out that, during the past decades, the discipline of immunology not only made great strides in the field of human medicine and experimental animal models associated with this branch of medicine but also in that of veterinary medicine. It was predicted that immunology would also continue to be essential in the diagnosis, treatment and prevention of disease in animals.

Animals↗
PubMed1979

Immunological surveillance against neoplasia: an immunological quandary.

Immunological endeavor in recent years calls for a reappraisal of the concept of immunosurveillance against neoplasia. This concept proposes an immunological policing system capable of aborting tumor growth by the recognition of "nonself" tumor associated antigens on neoplastic cells. The model is supported by evidence of tumor induction in the immunosuppressed host and the demonstration of an immune response to tumors in animals. The occurrence of tumor, regarded as a failure of immunosurveillance, is attributed to selection of neoplastic cells for immunological or other reasons or abnormal humoral or cellular antitumor immune responses. However protagonists of the postulate are faced with mounting evidence that fails to support the surveillance hypothesis. These observations include, inter alia, the monoclonality of certain tumors, the low incidence of spontaneous tumors in genetically immunodeficient mice and immunological privileged sites, and new ideas about the pathogenesis of lymphoproliferative neoplasms. However, contradictory arguments are not sufficiently substantiated to prosecute the case against surveillance conclusively. In citing highlights of the evolving quandary, both the pros and cons of immunological surveillance are presented here.

Animals↗
PubMed1978

Biological and immunological characterization of human luteinizing hormone: IV. Biological and immunological profile of two international reference preparations after electrofocusing.

The first IRP of Human Pituitary Gonadotrophins (FSH/LH) for bioassay (69/104) and the 1st IRP of Human Pituitary Luteinizing Hormone (LH) for immunoassay (68/40) were fractionated by an electrofocusing technique in a sucrose density gradient and the profile of biological and immunological activities was determined. The partially purified LH preparation (69/104) gave a broad pattern of biolgical and immunological activities which extended from pH 4 to 10. The biological : immunological (B/I) ratio of the various fractions (using the 68/40 preparation as standard) ranged from 0.04 to 1.05. The low B/I ratios indicate the presence of high levels of immunologically active, biologically inactive material in this preparation. In contrast to the behaviour of the 69/104 preparation, the major proportion (88%) of the biological activity recovered after electrofocusing of the highly purified LH preparation (68/40) was found within the pH range 7--9, with B/I ratios (again using as standard the 68/40 preparation) ranging from 0.4 to 1.5. Multiple dose parallel line design radioimmunoassays revealed a lack of parallelism between the 69/104 and 68/40 International Reference Preparations. This was attributed to the presence of acidic material in the former preparation, which is practically absent from the latter. The biological LH profiles of both the 69/104 and 68/40 preparations differed from those previously reported for aqueous extracts of pituitaries. It is concluded that the dissimilarity in the electrofocusing profiles of the biological and immunological activities of the 69/104 preparation renders this preparation unsuitable as a reference preparation for the quantitation of biologically active LH by radioimmunoassay methods. Using the same criteria, the 68/40 preparation would appear to be a more suitable standard.

Animals↗
PubMed1987

Nonrandom development of immunologic abnormalities after infection with human immunodeficiency virus: implications for immunologic classification of the disease.

Blood specimens from 165 intravenous drug users who were seropositive for the human immunodeficiency virus (HIV), from 158 seropositive homosexual men with lymphadenopathy, and from 77 patients with acquired immunodeficiency syndrome (AIDS) were assessed immunologically. Immunologic parameters were analyzed by the Guttman scalogram technique to determine if immunologic abnormalities occurred in a nonrandom pattern. The following four patterns emerged: (i) seropositivity for HIV with no immunologic abnormalities; (ii) seropositivity for HIV with a depressed T4/T8 cell ratio; (iii) seropositivity with a depressed T4/T8 cell ratio and T4-cell depletion; and (iv) seropositivity with a depressed T4/T8 cell ratio, T4-cell depletion, and lymphopenia. Ninety-two to 100% of subjects in each of the three groups of patients were found "to scale" because the abnormalities occurred in the cumulative, ordered fashion described. This nonrandom occurrence of abnormalities indicates an ordered progression of immunologic abnormalities in individuals infected with HIV, a finding useful in the staging of both symptomatic and asymptomatic HIV-seropositive subjects.

AIDS-Related Complex↗
PubMed2003

Modeling and predicting immunological effects of chemical stressors: characterization of a quantitative biomarker for immunological changes caused by atrazine and ethanol.

Previous studies demonstrate that the effects of one chemical stressor on selected immunological parameters can be predicted on the basis of the area under the corticosterone concentration vs. time curve. However, it is not clear if this is applicable to other chemical stressors. The present study was conducted to determine if the stress-induced immunological effects of atrazine and ethanol could be predicted, and if it is feasible to use one immunological parameter as a biomarker of stress to predict the quantity of changes expected in other immunological parameters. The area under the corticosterone concentration-versus-time curve (AUC) was measured in mice treated with ethanol (EtOH, 4, 5, 6, or 7 g/kg by oral gavage) or atrazine (ATZ, 100, 200, or 300 mg/kg, ip). The effects of the same dosages of these chemicals on thymus and spleen cellularity, lymphocyte subpopulations in the thymus and spleen, expression of MHC class II protein on splenocytes, antibody responses to keyhole limpet hemocyanin, and natural killer-cell activity were determined. Models were derived describing the relationship between corticosterone AUC and immunological changes induced by these chemicals. The results for these chemical stressors were more similar to results obtained from mice subjected to restraint stress than from mice treated with exogenous corticosterone. Some effects were greater than predicted on the basis of the stress response alone, indicating other mechanisms of immunotoxicity. One of the parameters (MHC class II expression) was evaluated as a predictive biomarker for stress-related immunosuppression, and the results suggest it could be suitable for that purpose.

Administration, Oral↗
PubMed1991

Month-related variability in immunological test results; implications for immunological follow-up studies.

This longitudinal study was originally designed to detect changes in the in vitro immune response of healthy subjects as a result of a psychological intervention. In this study a significant proportion, about 70%, of the immunological variability in the test results was accounted for by the differences in immunological response levels of the subjects. Apart from this between-subject-effect, a significant proportion of the variability in test results was related to the month of data sampling. The month-effect was computed in such a way that the between-subject variation was taken into account. This resulted in a more accurate estimation of the month-effect. Even after correction for the intervention, i.e. the defence of the PhD thesis, the effect of month of data sampling remains significant for mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, percentage of CD4 and CD8 cells, and for the response to the mitogens phytohaemagglutinin, pokeweed mitogen and concanavalin A as well as the results for the mixed lymphocyte culture for one pool out of three. In contrast, no significant month-effect was observed for the whole blood cell counts, for the differential white blood cell counts as determined by monoclonal antibody staining for cell surface markers CD3, CD16, TAC and OKM1, nor for the immunoglobulin IgM and IgG serum levels. Likewise the cell-mediated lympholysis activities measured against three pools of stimulator cells remained unaltered. We discuss the implications for future immunological follow-up studies of the observation that a significant proportion of the variability in immunological test results is related to differences between subjects and to the month of data sampling.

Adult↗
PubMed2005

Lessons from reproductive immunology for other fields of immunology and clinical approaches.

Reproduction is indispensable to evolution and, thus, life. Nonetheless, it overcomes common rules known to established life. Immunology of reproduction, and especially the tolerance of two genetically distinct organisms and their fruitful symbiosis, is one of the most imposing paradox of life. Mechanisms, which are physiologically used for induction of said tolerance, are frequently abused by pathogens or tumors intending to escape the host's immune response. Understanding the regulation of immune responses in pregnancy and the invasion of allogeneic fetus-derived trophoblast cells into the decidua may lead to new therapeutic concepts. In transplantation, knowledge concerning local physiological immunotolerance may be useful for the development of new therapies, which do not require a general immune suppression of the patient. In immunological disorders, such as autoimmune diseases or allergies, immune deviations occur which are either prevented during pregnancy or have parallels to pregnancy. Vice versa, lessons from other fields of immunology may also offer new notions for the comprehension of reproductive immunology and may lead to new therapies for the treatment of pregnancy-related problems.

Allergy and Immunology↗
PubMed1984

Bacterial histamine release by immunological and non-immunological lectin-mediated reactions.

The mechanisms of bacteria-induced histamine release were examined in vitro in human leukocytes and rat mast cells. Three types of bacterial responders were found. In persons with IgE-bearing basophilocytes bacterial histamine release could be triggered by two different mechanisms, an IgE-dependent mechanism where removal of IgE abolished the release and a non-immunological mechanism where this was not the case. In responders with no IgE-bearing cells bacterial histamine release was caused by a non-immunological mechanism. The non-immunological mechanism was further substantiated by release in isolated mast cells from germ-free rats. These experiments suggest a direct interaction between bacteria and target cell, and experiments with multi-washed bacteria and bacteria cell wall preparations indicate the possibility of the bacteria wall interacting with the target cell. It is probable that the non-immunological mechanism depends on lectin-mediated reactions, since bacteria-induced histamine release was inhibited by lectin-binding sugars as is release caused by plant lectins.

Basophils↗