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At least 361 records · Page 20Linked to original sources

Model approach to immunological rejuvenation of the aged.

Reconstitution of a damaged or exhausted immune system by injection of genetically compatible immunocompetent cells (immunologic rejuvenation) is a promising approach for restoration of immune activity. By using this model, spleen cells from young-adult mice, previously immunized with Salmonella typhimurium, were transferred to either young-adult or old, syngeneic recipients before or after storage at -196 C. The susceptibility of recipient mice was then determined by challenging them at increasing time intervals after reconstitution with lethal doses of the virulent organisms. The findings, although preliminary in nature, demonstrate that (i) immunological rejuvenation of mice is possible with immunocompetent cells from specifically immunized donors; (ii) prolonged "takes" of these cells can occur even in nonirradiated recipient mice, and (iii) storage at -196 C does not impair their protective capacity.

Aged↗

Murine and rat mammary tumors as models for the immunological study of human breast cancer.

The human breast cancer process and some aspects of experimental mammary cancer are compared in the light of Huxley's hypothesis that each neoplastic cell line may be viewed as a new obligate parasitic species derived from metazoan cells. Sufficient correlations are found to justify the hope that the viral-induced mouse mammary oncogenic process and the carcinogen-induced rat mammary system may serve as reasonable models of the human disease for immunological studies.

Age Factors↗

The search for pathogenic T cells and the genetic basis of psoriasis using a severe combined immunodeficient mouse model.

The immunologic and genetic bases of psoriasis are under active investigation throughout the world. Rather than pursue the genetic linkage to psoriasis to discover the gene(s) responsible for causing the disease, we have focused on the cellular immunology and basic biology using a novel animal model. We reasoned by identifying specific cellular and molecular abnormalities involved in the biologic responses that initiate lesion formation, that the genes involved in such a pathologic process would lead us to the correct causative DNA-based abnormality that determines disease susceptibility and inheritance. To pursue this line of inquiry, we utilized an animal model in which severe combined immunodeficient (SCID) mice were engrafted with symptomless skin (PN skin), and bona fide psoriatic plaques (PP skin) were created using specific pathogenic T cell subsets. This model can be used experimentally not only to study the mechanism by which PP skin is converted to PN skin, but also to create PP skin from PN skin. The clinical, histologic, immunologic, and pharmacologic validation of this SCID mouse model will be presented. This summary will also highlight the value of such a model, which has recently led to the discovery of previously overlooked types of immunocytes that are associated with induction of psoriatic lesions. Finally, a novel hypothesis linking the immunology and the genetics of psoriasis, based on findings using this animal model, will conclude this presentation.

Animals↗

Allogeneic kidney transplantation after active immunological enhancement: a model to study post-transplantation hypertension in rats.

A model was developed to study post-transplant hypertension after allogeneic kidney transplantation between two inbred normotensive rat strains. Prolongation of graft survival was achieved by 'active immunological enhancement'. Renal function, systolic blood pressure and plasma renin concentration were determined. The systolic blood pressure started to rise in the second week after allogeneic transplantation. The glomerular filtration rate was impaired to a greater extent than the effective renal plasma flow. Histopathological changes occurred indicating immunological reactions in the renal graft. The plasma renin concentration was lower in transplant recipients than in controls. We hypothesize that retention of sodium is mediately involved in the post-transplant hypertension observed in this model.

Animals↗

Spleen transplantation in the dog as a model for studying immunological feedback reactions.

Modification of the immune response towards the generation of suppressor T cells can be attained using experimental designs promoting immunological feedback mechanisms. Those studies have been carried out in defined inbred animal systems. With respect to the great importance for organ transplantation, an in vivo model using larger outbred animals was developed in order to study such feedback reactions. The following experimental design was used: (1) allogeneic spleen transplantation in the dog; (2) autologous retransplantation of this spleen together with an allogeneic kidney transplantation to the former donor of the spleen after a period of 2-4 days. Although full immunological activity of the transplanted as well as the retransplanted spleen was demonstrated, rejection of the kidney occurred in a fashion identical to that observed in control animals.

Animals↗

Immunologic reactivity to insulin: animal models and clinical syndromes.

Immunologic responses to insulin can be manifested by both laboratory animals immunized with insulin as a known modifiable model antigen and by patients receiving heterologous insulin as a mainstay of therapy for insulin dependent diabetes mellitus. The use of purified insulin as a model antigen for the study of cellular interactions, T cell antigen recognition, and the mechanism and specificity of Ir gene action in experimental animals has given us great insight into the potential workings of these complex functions. In humans with IDDM, immune cofactors may play a role in both the pathogenesis of disease as well as the obvious complications of therapy. Intense study of cellular, genetic, biochemical, and immunologic parameters in these patients with IDDM may provide us with unique insights into the complex regulatory interactions between the immunologic and endocrine-metabolic systems.

Animals↗

Intramuscular administration of recombinant adeno-associated virus 2 alpha-1 antitrypsin (rAAV-SERPINA1) vectors in a nonhuman primate model: safety and immunologic aspects.

We performed a series of studies in baboons to evaluate the safety of intramuscular administration of rAAV vector expressing the alpha-1 antitrypsin (AAT) gene (SERPINA1) in a nonhuman primate model. Initial experiments performed with an rAAV vector expressing the human SERPINA1 gene (at doses of up to 5 x 10(12) vector genomes/kg) resulted in the generation of anti-human AAT antibodies, which correlated with a loss of detectable transgene expression. Subsequent studies made use of the baboon SERPINA1 gene tagged with a short (10-amino-acid) c-myc tag. When animals were sacrificed, 4 months after vector injection, transduced myofibers showed efficient transgene expression without detectable humoral immune responses. Mild inflammation was observed in and near the sites of injection in some vector- and saline-injected animals, but serum creatine kinase (CK) values were normal in nearly every case. Real-time PCR was also performed 4 months after injection on gonadal tissue to evaluate the risk of germline transmission. No vector sequences were detected in the gonadal tissues from these animals. These studies indicate that the risks of immune reaction and germline transmission after intramuscular injection of rAAV-SERPINA1 in nonhuman primates are relatively low within the range of vector doses studied.

Animals↗

[Interactions between itch and pain].

The discovery of specific pathways for the processing of itch has greatly enhanced our understanding of the physiology of pruritus. However, the complex interactions between itch and pain are only partly understood. This review focuses on the neurophysiological basis of itch under experimental and clinical conditions. Chronic inflammatory diseases can locally sensitize nerve endings and thereby contribute to itch. In addition, there is increasing evidence that also central processing of itch can be sensitized in pruritus patients. Interestingly, this pattern of peripheral and central sensitization in pruritus has striking similarities to the one observed in chronic pain patients. The presumed similarities in underlying sensitizing mechanisms between itch and pain has major therapeutic consequences as successful therapies for chronic pain might be used also in chronic itch.

Humans↗

[Neurophysiology of pruritus].

Neurophysiologic studies indicate that pruritus is a distinct sensation with its own neuronal pathways in the peripheral and central nervous system which are different from that of pain. Pruritus is a very disturbing sensation and most common skin-related symptom. Histamine was long considered to be the only mediator of pruritus. However, it has become evident that - besides histamine - a variety of neuromediators such as neurotrophins and neuropeptides as well as their receptors play an important role in pruritus. Neuromediators are produced by mast cells, keratinocytes and eosinophil granulocytes which are in close contact to sensory nerves. The discovery of these neurophysiological interactions opens new and promising therapeutic options for the treatment of pruritus.

Humans↗

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↗

[Potential use of a mathematical modeling method for the analysis of immunological phenomena].

The paper reviews mathematical models of immunological processes associated with reactions of the total immunity system and its single formations: infectious diseases, in vivo experiments with cell cultures, cell proliferation and differentiation in the thymus, primary and secondary immune responses to the antigen, immunodeficient states, etc. It also gives models of immunological reactions in vitro: precipitation, agglutination, plaque formation, etc. The paper contains a short description of potentialities of mathematical models of biological processes.

Aerospace Medicine↗

Immunologically induced tubulo-interstitial nephritis: experimental models in rats.

Experimental models of immunologically induced tubulo-interstitial nephritis (TIN) in rats are described. Antitubular basement membrane (anti-TBM) nephritis was demonstrated to be a TIN resulting from an antigen antibody reaction. Renal transplant rejection and the local graft-vs-host (GVH) reaction were cell-mediated immune reactions in which the antigen was possibly shared by kidney structures. A cellular immune reaction to locally applied antigens was shown to be the basis for another experimental model of TIN, possibly originating from activated mediator systems.

Animals↗

An animal model of occupational immunologic asthma due to diphenylmethane diisocyanate, with multiple systemic immunologic responses.

Inhalation of MDI in the plastics industry may produce hypersensitivity pneumonitis or immediate-type asthma in workers. A suspension of MDI was given intrabronchially to dogs to determine whether any of the clinical and immunologic human responses could be duplicated, Results showed that dogs produce a systemic immune response to MDI-DSA. Serum MDI-125I-DSA binding was shown by the ammonium sulfate binding technique. Antibody activity of IgG, IgA, and IgM antibody classes was shown by a solid-phase enzyme-linked immunoassay. Precipitating antibodies were detected in he dog serum against MDI-DSA. Immediate-type skin reactivity to MDI-DSA consistent with a canine IgE response occurred. The skin reactivity appeared to correlate with an immediate-type airway response characterized by an increase in pulmonary resistance after intrabronchial MDI. There was transient peripheral blood lymphocyte reactivity to MDI-DSA. The results indicate that a large animal model of human immune response to MDI is available for various immunopathogenic studies.

Airway Resistance↗

Xenogeneic and allogeneic canine heart transplantation: a model for cytologic and immunologic monitoring of rejection mechanisms.

In the model of heterotopic intrathoracic heart transplantation, rejections of the graft are not lethal for the recipient animal. Therefore it is possible to follow the immunologic rejection mechanism to the final stage. Allogeneic dog hearts (n = 6) and xenogeneic fox hearts (n = 6) were transplanted. Immunosuppression therapy included cyclosporine and methylprednisolone. Cytoimmunologic monitoring was done every second day. Due to fluctuations of lymphocyte subpopulations and their immature forms, endomyocardial biopsies were performed. The transplanted allogeneic hearts survived for 53.2 +/- 14.8 days if treated with cyclosporine (historical control group without immunosuppression 6.8 +/- 0.8 days). Xenogeneic fox hearts stopped beating after 20.2 +/- 4.1 days (historical control 8.4 +/- 1.9 days). The allogeneic grafts were all rejected in an acute cellular fashion, whereas xenogeneic transplanted hearts showed humoral and cellular rejection mechanisms. Monitoring of circulating inflammatory cells allowed differentiation between humoral and cellular rejection, which was confirmed by histology. Both types of rejection were accompanied by an increase of lymphocytes and their activated forms. Differentiation of lymphocyte subpopulations revealed a significant increase of surface IgG-positive B-lymphocytes under humoral rejection, whereas acute cellular rejection episodes showed a substantial increase of surface IgG-negative lymphocytes. Humoral rejection that developed even with cyclosporine administration was not influenced, whereas cellular rejections were controlled by increasing methylprednisolone to 250 mg/day for 3 days.

Animals↗

Experimental immunological intrahepatic cholestasis model.

Heat-killed Propionibacterium acnes (P. acnes) was intravenously injected into tuberculin-sensitized guinea pigs, and 7 days later, purified protein derivative (PPD) was also injected intravenously resulting in marked reductions in bile flow and bile acid excretion. Serum levels of bile acids and cholesterol were increased, and the activities of alkaline phosphatase (ALK-p) and leucine aminopeptidase (LAP) were also elevated. Histological examination revealed dilatation of bile canaliculi and diminution of microvilli. These results indicated that intrahepatic cholestasis was induced. These pathological changes were not detected in guinea pigs in which PPD was not injected. In this experimental model, the tuberculin-sensitized lymphocytes were infiltrated into the liver by P. acnes injection and the cholestatic factor was produced by PPD injection, resulting in the induction of intrahepatic cholestasis.

Animals↗