Immunologic models to study cardiac allograft rejection and prolongation.
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Animals↗
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Results for “Models, Immunological”
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In vitro correlates of rejection. III. Immunologic models for the study of a variety of kidney and heart transplant rejection and prolongation phenomena.
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Animals↗
[Experimental immunologic models in nephropathology].
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Animals↗
[Antitumor immunity elicited by 4-1BBL gene transfected Hepa1-6 in vivo].
OBJECTIVE: To study the effects of 4-1BBL on antitumor immunity induced in vivo by murine 4-1BBL gene transfected Hepa1-6. METHODS: Retrovirus vector was used to transfer the 4-1BBL gene into syngeneic murine heptocellular carcinoma cell line Hepa1-6. The products were termed as Hepa1-6/4-1BBL, and then the TCV4-1BBL was obtained by treating them with mitomycin (MMC). Three models (immunological model, early model, and later model) were established to study the antitumor effects of TCV4-1BBL. RESULTS: (1)In immunological models, the syngeneic mice were completely protected by inoculation with TCV4-1BBL, survived free from tumor for a long period (over 100 days). (2)In early models (7 days after inoculation), Hepa1-6 tumor cells showed strong immunogenicity effects and (3) In later models (14 days after inoculation), they had obvious antitumor effects and most of the tumors were disappeared. CONCLUSIONS: The antitumor effect against syngeneic murine hepatocellular carcinoma in vivo is obviously enhanced by treating them with TCV4-1BBL
4-1BB Ligand↗
Computational models in immunological methods: an historical review.
The utilization of computational models in immunology dates from the birth of the science. From the description of antibody-antigen binding to the structural models of receptors, models are utilized to bring fundamental understandings of the processes together with laboratory measurements to uncover implications of these data. In this review, an historical view of the role of computational models in the immunology laboratory is presented, and short mathematical descriptions are given of fundamental assays. In addition, the range of current uses of models is explored -- especially as seen through papers which have appeared in the Journal of Immunological Methods from volume 1 (1971/1972) to volume 208 (1997). Each paper which introduced a new mathematical, statistical, or computer simulation model, or introduced an enhancement to an instrument through a model in those volumes is cited and the type of computational model noted.
History, 20th Century↗
[The immunological synapse: models facing facts].
The notion of immunological synapse is generally associated to a concentric structure (a core of T cell receptors surrounded by a ring of adhesion molecules) often called "mature synapse". This schematic view has been built on observations corresponding to peculiar experimental conditions: very high antigen concentration presented by surrogate APCs such as lipid bilayers or B lymphoma. These observations have been hastily constituted in a dogma that a "normal" synapse should look like this, should form only in the presence of antigen, and should trigger a "stop" signal that completely immobilizes the T cell. However, when analyzing the interaction between naive T cells and dendritic cells (DC), that are the only antigen-presenting cells able to activate naive T cells, a very different picture emerges. Firstly, T-DC synapses can form in the absence of antigen; therefore antigen recognition is not a prerequisite for synapse formation. Secondly, these antigen-independent synapses are likely to play several roles, including sensitization of T cells for later antigen detection, and delivery of survival signals. Thirdly, in vivo, naive T cells interacting with antigen-laden DC do not fully stop, but start to make transient contacts with DCs for a few minutes, before continuing their exploration. It is only after several hours of this process that T cells eventually immobilize. Fourthly, the structure of the T-DC synapse is clearly multifocal, the two cells interacting through several tens of tight appositions of a few tens of nm in diameter. These numerous tight appositions are reminiscent of the microclusters that have been recently described at the T-bilayer interface. Finally, synaptic signaling is not a transient initial event, but is sustained for hours. In particular, sustained activation of phosphatidylinositol 3-kinase allows the exclusion out of the nucleus of FoxO transcription factors, normally maintaining T cells in a quiescent state.
Animals↗
Application of mathematical model of immunological tolerance to HIV infection.
Our experimental model of immunological tolerance to non-reproducing antigens is based on the assumption that tolerance is caused by elimination or irreversible inactivation of lymphocytes reacting specifically with the tolerance inducing antigen, and that recovery from tolerance is due to the spontaneous maturation from the stem cells of new lymphocytes reacting with the tolerated antigen. The recovery starts, when the antigen is eliminated from the organism and does not induce tolerance in newly arising lymphocytes any more. Here we report the application of this model to the depletion of CD4+ lymphocytes in persons infected with HIV. This depletion seems to be effected either directly or indirectly by HIV products. Therefore, the dynamics of this depletion can be described by the equations characterizing the dynamics of lymphocytes exposed to tolerance inducing antigen, when HIV products are substituted for antigen. In contrast to non-replicating antigens, the concentration of HIV products increases, as the infection progresses. In consequence, the CD4+ lymphocyte depletion increases with time and its dynamics are reciprocal to those of tolerance to non-reproducing antigens, which decrease with time.
Acquired Immunodeficiency Syndrome↗
Action of mannitol in various immunological experimental models.
The authors describe the inhibiting action of mannitol after repeated administration of low subcutaneous doses in a number of experimental immunological models. For example, in the rat it produces a reduction of the secondary arthritis of Freund's adjuvant polyarthritis and also of the pleurisy due to Bordetella pertussis hypersensitivity. In the mouse it reduces the reaction of delayed hypersensitivity to sheep red cells. Its action is also marked against ovalbumin-induced active skin anaphylaxis in the albino guinea-pig and on IgE synthesis in the rat. Moreover, after several injections it produces a reduction of carbon phagocytosis in the mouse. At the doses at which the effect appeared, no action could be found on various models of acute non-immune inflammation, diuresis, blood pressure, hematocrit and protein and plasma sodium levels.
Acute Disease↗
Experimental spironucleosis (hexamitiasis) in the nude mouse as a model for immunologic and pharmacologic studies.
Experimental infection of the nude (nu/nu) mouse with the intestinal flagellate, Spironucleus (Hexamita) muris, was used as animal model for immunologic studies and for the testing of protozoa cides. The fecal discharge of cysts was shown to correlate with the immune status of the host. It was dependent on the strain, presence of the thymus (nu/nu and nu/+), and age (immunologic maturity). Four protozoacides (dimetridazole, metronidazole, tinidazole, and chlormethoxyacridylamino-diethylaminopropanol-dihydrochloride) were tested in infected mice. All lowered or suppressed the fecal discharge of cysts during treatment; however, the cysts reappeared in the feces when treatment, lasting 1-3 weeks, was terminated. It was concluded that experimental infection of the nude mouse with S muris was an excellent model for immunologic and pharmacologic studies.
Animals↗
Adenocarcinoma R-3327 of the Copenhagen rat as a suitable model for immunological studies of prostate cancer.
An experimental animal model for the study of host-prostatic tumor cell interactions has been described. R-3327, a line of prostatic adenocarcinoma of the Copenhagen rat, has been proven to be immunogenic to its syngeneic host as evidenced by two different in vitro cell-mediated immune assays. Specificity of the responses has been ascertained on the basis of absence of response: (a) of nonimmune lymphocytes to the R-3327 tumor antigen(s); (b) of R-3327 immune lymphocytes to several normal tissues including normal prostate; (c) of immune lymphocytes to unrelated squamous cell prostatic carcinoma of the Copenhagen rat. Furthermore, the presence of tumor has an effect in several nonspecific aspects of host response, inducing splenomegaly, heightened responses to nonspecific mitogens in lymphocyte transformation assay, and increased levels of killer cell action. Since there are many histological, biochemical, and functional analogies between this tumor line and human prostate carcinomas, this system appears to be suitable for immunological and possible immunotherapeutic studies of this type of neoplasia.
Adenocarcinoma↗
Correlations among expression of intercellular adhesion molecule 1, cellular infiltration, and coronary arteriosclerosis during chronic rejection using the rat heart transplantation model.
Immunologic mechanisms contribute to the development of coronary arteriosclerosis. In this study the rat heart transplantation model was used to investigate correlations among the expression of intercellular adhesion molecule 1, cellular infiltrate, and coronary arteriosclerosis during chronic rejection. Lewis rats served as heart donors and F-344 rats as recipients. Heart transplantations were performed heterotopically. The recipients were treated with cyclosporin A (5 mg/kg/day) by daily intramuscular injection for 30 days, beginning on the day of transplantation. Rejection grade and the intimal area were measured. The expression of intercellular adhesion molecule 1 and the numbers of infiltrating CD4- and CD8-positive cells and macrophages were examined immunohistochemically. The area of the intima was significantly increased in the allograft group after transplantation. In the allograft group, the level of expression of intercellular adhesion molecule 1 was considerably increased over the same time period. There was increased cellular infiltration in the 60-day group, and many expressed intercellular adhesion molecule 1. The expression of intercellular adhesion molecule 1 in vascular endothelium, infiltrating cells, and the sarcolemmal membrane of myocytes remained constant up to 120 days in the allograft group. In the allograft group, the number of infiltrating CD4- and CD8-positive cells and macrophages increased significantly between 30 and 60 days, and the infiltration of these cells remained constant. Continuous expression of intercellular adhesion molecule 1 induces the infiltration of T cells and macrophages, and the inflammation caused by such cells and their soluble products contributes to the arteriosclerotic process.
Animals↗
A contribution to mathematical modelling of immunological tolerance.
The original simple mathematical model describing the kinetics of B cell tolerance was extended by the inclusion of Th cell tolerance. It anticipates the existence of two compartments of B and Th cells reactive to the antigen--the immature cells and the mature ones. It is assumed that tolerance is induced by irreversible inactivation of the antigen-reactive cells and the escape from tolerance is due to their differentiation from the precursors. There is also considered the situation, where two categories of Th cells cooperate with the same B cells. Besides that, suppressive activity on Th cells is included in the model. The simulated values are compared with experimental data.
Animals↗
GATA-3 transcriptional imprinting in Th2 lymphocytes: a mathematical model.
Immunological memory involves the fast recall of cytokine expression by T helper (Th) lymphocytes. Two distinct profiles of cytokine expression, Th1 and Th2, can be induced by antigen and polarizing signals during activation of naive Th cells and can subsequently be reexpressed on stimulation by antigen alone. The transcription factor GATA-3 induces Th2 development. GATA-3 is activated by the Th2-polarizing stimulus, IL-4, and has recently been observed to autoactivate its transcription. Based on these experimental data, we developed a mathematical model of GATA-3 expression that assumes independent activation of GATA-3 transcription by IL-4 and by GATA-3. Cooperativity of GATA-3 transcriptional activation is shown to create a threshold for autoactivation, resulting in the coexistence of two distinct GATA-3 expression states: a state of basal expression and a state of high expression sustained by autoactivation. Suprathreshold IL-4 signals induce a transition from basal to high GATA-3 expression. Thus, GATA-3 autoactivation creates a bistable system that can memorize a transient inductive signal. The model further predicts conditions under which the state of high GATA-3 expression can be abolished, which may extinguish the Th2 cytokine memory.
Animals↗
Spleen autotransplantation in mice: a novel experimental model for immunology study.
The aim of the experimental model to develop a spleen transplant model in mice to study the role of spleen in autoimmune and transplant rejection. After a midline incision, splenectomy was performed. Four tiny segments were cut from the removed spleen and were rinsed at room temperature in physiological salt solution. The greater omentum was lifted and four omental pockets were created; four thin segments were then placed into the "nests," subsequently marked, and fixed using 8-0 suture. The abdomen was then closed. The duration of the survival time was different among the nine groups (n = 3-3). Tissue samples were taken from the marked areas for histological examination stained with hematoxylin and eosin (H&E). H&E staining demonstrated large, well-circumscribed splenic nests with lymphoid zone and red pulp and well-formed trabecules in the spleen. Among the possible applications of this novel model is the ability to study the role of spleen in autoimmune and organ rejection.
Animals↗
African hamster lymphocytes as a model for immunologic studies.
The mitogenic response of splenic lymphocytes from Mystromys albicaudatus was studied to evaluate the potential of this animal as a model for immunologic research. In response to phytochemagglutinin and concanavalin A, splenic cells from Mystromys, unlike those from mouse strains, incorporate [3H] thymidine optimally in microculture at 10(5) to 2 X 10(5) cells per microculture. Maximum magnitude of incorporation in response to the same doses of mitogen used in mouse splenic lymphocyte microculture is greater than 10(5) cpm. Moreover, this high incorporation at low cell concentration has been observed in cultures from animals ranging from six to 24 months of age. Splenic cells from Mystromys give little or no incorporation with either LPS or PPD in doses mitogenic to mouse lymphocytes. These features of mitogenic response in Mystromys lymphocyte cultures suggest several useful applications to studies of mechanisms of mitogenesis.
Animals↗
[Critical analysis of the immunological self/non-self model and of its implicit metaphysical foundations].
An examination of the concepts used in immunology prompts us to wonder about the origins and the legitimacy of the notions of self and non-self, which constitute the core of the dominant theoretical model in this science. All theoretical reflection concerning immunology must aim at determining a criterion of immunogenicity, that is, an operational definition of the conditions in which an immune reaction occurs or does not occur. By criticizing both conceptually and experimentally the self/non-self vocabulary, we can demonstrate the inaccuracy and even the inadequacy of the dichotomy of self/non-self. Accordingly, the self/non-self model must be reexamined, or even rejected. On the basis of this critique, we can suggest an alternative theoretical hypothesis for immunology, based on the notion of continuity. The 'continuity hypothesis' developed here attempts to give a criterion of immunogenicity that avoids the reproaches leveled at the self model.
Animals↗
[Uncertainties about the self and the issue of the proper theoretical model in immunology].
Theoretical immunology constitutes a critical basis of all medical discoveries. Immunology has been dominated since the 1940s by the self/nonself model. Here we try to shed light on the origins of this theoretical model and to show how and why this model has been called into question during the last thirty years. This paper has three aims. Firstly, we explore the sources of the immune self, going upstream from immunology to ecology-biology, psychology and eventually philosophy. Here the key questions : is the immune self really analogous with the philosophical and psychological selves in which it originates? What is the signification and adequacy of such a conceptual borrowing? We suggest that the << self >> vocabulary in immunology is not clear and precise. Secondly, we present the experimental inadequacies of the self/non-self model. We show then how both the vagueness of the term << self >> and these experimental flaws casted doubt on theories of immunology. Among the several models that have been proposed recently, none has attracted a consensus. Some immunologists have even suggested that immunology should rid itself of theorical concerns and concentrate on molecular aspects. This suggestion, however, is unacceptable\; hence it is still necessary to find a theoretical framework for immunology. Finally, we try to suggest a way to escape this uncomfortable situation of doubt. The immune << self >> and the immune << system >> (<< network >>) are rooted in strong metaphysical conceptions of identity, the main characteristic of which is to consider the organism as an enclosed and self-constructing entity. By contrast, based on experimental data about immune tolerance and host-pathogen interactions, we propose to consider organisms as open entities. To what theory does this conception lead? What would be the consequences of such a theory with regard to medical aspects?
Allergy and Immunology↗
[APROPOS OF TUMOR IMMUNOLOGY. (A MODEL)].
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Humans↗