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Dependence of cell-mediated immune lysis of the EL-4 ascitic lymphoma on its population composition and rhythm.

Investigations on cell-mediated immune release of 51Cr from the EL-4 ascitic lymphoma showed that daily rhythmic changes can be correlated with the dominance of certain cell types in the population. Cells in compartment 1--i.e., those representing true G0, early G1, S and M--are most sensitive to effector cell attack. During the establishment 96-hour appearance cycle of the population, each day a different compartment will predominate, with corresponding variations in percent immune release. On days when spontaneous 51Cr release shows a maximum, immune release is minimal. The differences between maximal values of immune release may reach more than 300%, when findings from different days in the appearance cycle are compared.

Animals↗

Cells involved in the immune response. XXVIII. the cellular composition of the lymphoid organs in the normal outbred rabbit.

Horse anti-rabbit spleen cell antiserum was obtained by the intravenous immunization of horses with rabbit spleen cells. The antisera obtained were analysed for their lymphocytotoxic activity with respect to the lymphoid cells of the different lymphoid organs prior to and following absorption with the different lymphoid cells. The results have been integrated with those obtained in previous investigations and an all-embracing concept of the interrelationship of the lymphoid cells in the different lymphoid organs in the rabbit has emerged. The distinction between the heretofore considered central lymphoid organs (bone marrow and thymus) and peripheral lymphoid organs (spleen, lymph node and appendix) has been blurred by the finding that, at least in the rabbit, appendix cells possess specific antigen markers and participate in cell-mediated immune reactions in vitro and the observation that the spleen also has a central lymphoid function in the generation of cells in vivo capable of carrying out a cell-mediated immune reaction in vitro. It is concluded that the distinction of central and peripheral lymphoid function may be an artificial one in that it may reflect a function of the particular organ in only one of the many different types of immune reactions and that it should not influence the investigator in the elucidation of the cellular mechanisms participating in the mediation of the different immune responses.

Absorption↗

Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma.

In the present study, epithelium derived lesions of various pathological manifestations were examined histologically and immunohistochemically for mononuclear cell infiltration. The infiltrate under the transformed epithelium of oral lesions, was examined for differences in the composition of immune mononuclear cells as the epithelium moves from hyperkeratosis through various degrees of dysplasia to squamous cell carcinoma. The study was performed on 53 human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19 cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases). Immunohistochemical analysis of various surface markers of the tumour infiltrating immune cells was performed and correlated with the transformation level as defined by morphology and the expression of p53 in the epithelium. The results revealed that, in the tongue lesions, the changes in the epithelium from normal appearance to transformed were accompanied by a corresponding increase in the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most significant change was an increase in B lymphocytes in tongue lesions, that was in accordance with the transformation level (P<0.001). In the salivary gland, a significant number of cases did not show an infiltrate. In cases where an infiltrate was present, a similar pattern was observed and the more malignant tissues exhibited a higher degree of immune cell infiltration.

Carcinoma↗

Regulation of the immune response in Plasmodium falciparum malaria. III. Proliferative response to antigen in vitro and subset composition of T cells from patients with acute infection or from immune donors.

T cells from patients with acute Plasmodium falciparum malaria were investigated for their proliferative responses in vitro to malarial antigen. Of 26 patients, 14 had acute and short lived (less than or equal to 8 days) disease episodes, most of them for the first time, while 12 had been ill for more than 8 days at the time of the blood samples were taken. The lymphocytes from the first group gave a weak, and apparently P. falciparum specific proliferation, peaking after 3-4 days, but waning within 5-6 days, suggesting the induction of suppression. No such responses were obtained with control antigen consisting of normal RBC membranes. The P. falciparum antigen-induced proliferative response was completely lacking in the second group of patients. Since both groups responded equally to T cell mitogen, the results are indicative of a malaria specific non-responsiveness. In contrast T cells from a group of apparently immune donors living in highly endemic P. falciparum malaria areas developed strong and long lasting proliferative responses to P. falciparum antigen with a peak on days 5-6. T cells from acutely infected P. vivax patients did not respond to either the P. falciparum antigen or to the control antigen. The cellular basis of the proliferative responses were investigated by surface marker studies with monoclonal antibodies. Within the T cell preparations, the T4+/T8+ cell ratio was close to normal for both the immune donors and for those with acute P. vivax infection. In contrast, this ratio was depressed for both groups of patients with acute P. falciparum infection. However, this was due to reduced number of circulating T4+ cells in the patients with short disease episodes whereas it was due to increased numbers of T8+ cells, probably including suppressor cells, in those who were ill for more than 8 days.

Antibodies, Monoclonal↗

[Regulating effect of pineal gland peptides on development of T-lymphocytes in CBA aging mice: role of microenvironment of immune system organs and neuroendocrine factors].

Studies were undertaken on the development of T-lymphocytes in adult and old CBA mice and its changes at aging after injections of pineal gland peptides. It was shown that in old mice the disturbances of T-cells differentiation are registered in bone marrow, thymus, spleen and characterized by the changes of lymphocyte markers expression, migration and proliferation of cells. In old mice FTS titer, melatonin and testosterone levels decreased, the balance of noradrenalin and serotonin in hypothalamus and the cell composition of microenvironment immune systems organs impaired. After chronic (18 mo) administration of the pineal gland preparation epithalamin the amount of stromal cells-precursors, CD4+ and Mac-1(+)-cells in old bone marrow increased, improved the migration of T-cell precursors from bone marrow to thymus and their proliferative potential. The proportion of CD3+, CD4+CD8-, CD4-CD8+, Mac-1(+)-cells in old thymus increased, while that of CD44(+)-cells decreased. The proportion of CD4-CD8(+)-cells in spleen increased. The most number of indices and their balance showed a pattern of adult mice. In old mice after epithalamin the balance of amines in hypothalamus improved, concentration of melatonin in pineal gland, testosterone and FTS titer in blood increased. Epithalon has also the possibility to increase of thymic endocrine function.

Aging↗

The neonatally T cell receptor 2-suppressed rat: lymphocyte subset composition and immune reactivity.

Rats were injected intraperitoneally from birth on with a mouse monoclonal antibody (R73) to a constant determinant of the rat T cell receptor (TcR)2. Throughout the observation period (6 months), TcR2+ cells in peripheral lymphoid organs and blood were absent in treated animals with the exception of few (less than 10%) cells with a tenfold reduced TcR2 density; peripheral TcR2-CD3+ cells, i.e. most likely TcR1+ T cells, were increased in frequency. Among thymocyte subpopulations, only those expressing the TcR2 at a high level were reduced in number. The lack of a visible effect on immature thymocytes may, however, be due to the fact that despite high serum levels, thymic R73 determinants were incompletely saturated. Spleen and lymph node cells from TcR2-suppressed rats were completely unresponsive in mixed lymphocyte reaction (two fully allogeneic haplotypes tested) even in the presence of interleukin 2. Reactivity to the T cell mitogen concanavalin A was, in contrast, only partially reduced. Since rat TcR1 cells are activated by concanavalin A, these results suggest that the TcR1 cells present in TcR2-suppressed rats are functional, but do not respond to foreign major histocompatibility complex antigens at a high frequency, a finding of possible importance for immunosuppression with anti-TcR2 monoclonal antibody in human allografting. Neonatally TcR2-suppressed rats were unable to respond to the strong T-dependent antigen keyhole limpet hemocyanin administered intraperitoneally in alum with B. pertussis. Thus, in the absence of peripheral TcR2 cells, the numerically expanded TcR1 T cells are not capable of providing help for B lymphocytes.

Animals↗

Polyunsaturated fatty acids, inflammation, and immunity.

The fatty acid composition of inflammatory and immune cells is sensitive to change according to the fatty acid composition of the diet. In particular, the proportion of different types of polyunsaturated fatty acids (PUFA) in these cells is readily changed, and this provides a link between dietary PUFA intake, inflammation, and immunity. The n-6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds, which have important roles in inflammation and in the regulation of immunity. Fish oil contains the n-3 PUFA eicosapentaenoic acid (EPA). Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA-derived mediators. In addition, EPA is a substrate for cyclooxygenase and lipoxygenase and gives rise to mediators that often have different biological actions or potencies than those formed from AA. Animal studies have shown that dietary fish oil results in altered lymphocyte function and in suppressed production of proinflammatory cytokines by macrophages. Supplementation of the diet of healthy human volunteers with fish oil-derived n-3 PUFA results in decreased monocyte and neutrophil chemotaxis and decreased production of proinflammatory cytokines. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease. Clinical studies have reported that fish oil supplementation has beneficial effects in rheumatoid arthritis, inflammatory bowel disease, and among some asthmatics, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory and immunomodulatory.

Animals↗

Chronological assessment of asbestos exposure on cell composition in murine lung.

To elucidate immune pathogenic mechanisms in asbestosis, lung and spleen lymphoid cell populations were analyzed at defined time intervals (1, 2, 3, 6, and 12 weeks during exposure and 4, 24, and 48 weeks post-exposure) in asbestos-exposed and unexposed (control) mice. Polymorphonuclear leukocytes and macrophages were increased in the lung tissue histologic sections of asbestos-exposed mice compared to controls. No consistent changes were observed in percentages of lung or spleen helper, suppressor, or total lymphocyte populations after asbestos exposure. The numbers of B cells (identified by anti-IgG) in minced lung preparations of asbestos-exposed animals were increased after 12 weeks of exposure. There also was an increase in IgG production in asbestos-exposed mice after 12 weeks exposure and at 4 weeks post-exposure with a return to near baseline levels 24 and 48 weeks after initial exposure. Collectively, these studies demonstrate stimulatory effects of inhaled asbestos fibers on B cells and IgG production after 12 weeks of continuous inhalation of asbestos fibers in a dust generation chamber.

Animals↗

Construction of a new predictive model in head and neck squamous cell carcinoma based on the investigation of extracellular matrix-associated genes.

A key aspect influencing immune cell infiltration is the composition of the extracellular matrix (ECM). Therefore, investigating the association between ECM-associated proteins and immune cell infiltration is key for the identification of new biomarkers to distinguish 'immune-hot' solid tumors and predict patient prognosis. A total of 513 head and neck squamous cell carcinoma (HNSCC) cases as training samples from The Cancer Genome Atlas and an additional 270 as testing samples from the Gene Expression Omnibus were obtained for use in the present study. Using a single-sample Gene Set Enrichment Analysis method, the 513 training samples were divided into Cluster 1 and Cluster 2. Subsequently, the present analysis uncovered 1,573 differentially expressed genes distinguishing the two clusters. After performing an intersection analysis with 751 ECM-associated genes, 103 differentially expressed ECM-associated genes were identified. Least absolute shrinkage and selection operator-Cox and multivariate Cox regression analyses were employed to identify candidate ECM risk genes (P<0.05) and to construct a predictive model. Finally, a nomogram and a three gene (cerebellin 2, galectin-10 and cathepsin G) predictive model were developed. Therefore, the present prognostic risk score model can evaluate the immune infiltration, predict the prognosis of HNSCC, and potentially guide more personalized immunotherapy interventions.

extracellular matrix↗

[Response of immune system and lymphoid tissue of respiratory and gastrointestinal organs to space flight factors].

The studies demonstrated that gamma-radiation drastically enhanced destructive processes and suppressed the mitotic activity of lymphocytes in the thymus and spleen. This resulted in the altered morphological picture of immune organs: the inversion of layers occurred in the thymus, the splenic white pulp increased by three times, lymphoid nodules with germinating centers disappeared, the marginal area became thinner. Following gamma-radiation, restorative processes in the thymus and spleen were noticeable just on day 3 and 7, respectively. However, the cell composition of murine immune organs failed to achieve control values by day 60 after exposure. Examining the responses of respiratory and digestive lymphoid tissue to acetaldehyde and drinking water organisms indicated that as the concentration of an acting agent and the time of exposure increased, there was lymphocytopoietic inhibition in the lymphoid formations whereas its small doses activated a local immune response.

Animals↗

Immunogenic combinations of HIV-1 B- and heterologous T-cell epitopes.

Peptides were synthesized which combined HIV-1 B-epitopes from gp41, p34pol and heterologous T-cell epitopes from hepatitis B virus (HBV) core or tetanus toxoid. Mixtures of these composite peptides and peptides representing single HIV-1 B-epitopes were used to immunize rabbits in an adjuvant-free immunization regimen. Fusion to T-cell epitopes made the HIV-1 B-epitopes immunogenic and high titers of anti-HIV-1 antibodies were reached. Efficient antibody response against an immunorecessive HIV-1 B-epitope from p34 pol introduced as a B+T-composite also developed in rabbits pre-immunized by composites of the same T-cell epitopes but with a B-epitope from gp41. Fusion changed the fine antigenicity of the epitopes, but at least part of the antibodies against gp41-containing B+T composites recognized whole viral gp160. Composite peptides stimulated T-cells in the majority of the immunized animals.

Amino Acid Sequence↗

Altered allogeneic immune responses in middle-aged mice.

It is well known that leukocyte composition, T cell phenotypes and immune function change in aged mice and humans. However, limited and conflicting results on the age-related immune changes in middle-aged mice were reported. Identification of the characteristics of allogeneic immune responses in aging mice may offer important information for transplantation immunology. The major age-related changes in the immune cell phenotypes and function of 12 months old mice include: 1) the significantly decreased CD4+ cell population in the peripheral blood, the major peripheral CD4+ cells is CD45RB(low)CD62L(low) memory phenotype; 2) the in vitro responses to alloantigens and Con A of splenocytes markedly reduced; 3) the in vivo secondary humoral immune responses to alloantigens significantly declined; 4) the age-related alteration in the thymus mainly occurred in CD4/CD8 double positive (DP) stage; and 5) increased CD80+ and MHC class II+ cell population in spleens. Thus, the major age-related immune changes in 12 months old mice occurred in CD4+ T cells in the periphery and DP stage in the thymus, which may subsequently lead to the decreased allogeneic immune responses and the different sensitivity to immunosuppressive drugs and treatments. Further studies on the characteristics of allogeneic immunity in aging individuals may help to determine the appropriated treatment for transplant aging individuals.

Aging↗

[The role of cytokines at the fetomaternal interface].

Various mechanisms are necessary for regulating the survival of the semiallogenic embryo in the maternal organism. In addition to the lack of classical MHC class I and II antigens at the trophoblast the cytokines play an important role at the fetomaternal interface. Different cytokines regulate the immunological processes with an emphasis on the Th1/Th2 balance. In contrast to the peripheral blood there is a certain composition of immune competent cells at the fetomaternal interface. There are many different interactions between the endocrine and immunological system. Hormones modulate the secretion of certain cytokines and vice versa. In reproductive medicine it is of specific interest to evaluate these functions for treating problems during the early pregnancy.

Cytokines↗

Predicting diagnostic gene biomarkers associated with immune infiltration in patients with diabetes.

Diabetes is a global public health problem with various complications, which can lead to disability and mortality. This study identified potential diagnostic markers for diabetes and explored the immunometabolic mechanisms in the pathological process. The gene expression of 17 diabetes cases and 16 normal controls were obtained from the Gene Expression Omnibus (GEO) database. The "limma" package was employed for screening differentially expressed genes (DEGs). Gene functions and enriched pathways of DEGs were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Candidate key genes were screened using the least absolute shrinkage and selection operator (LASSO) regression model and support vector machine recursive feature elimination (SVM-RFE) analysis. The diagnostic effectiveness of identified markers was further verified via the receiver operating characteristic (ROC) curve. The compositional patterns of immune cell infiltration and signaling pathway enrichment associated with key genes were explored via single sample Gene Set Enrichment Analysis (ssGSEA) and GSEA analysis, respectively. Possible miRNAs interacting with key genes were predicted via miRcode database. B2M, FTL, SH3BGRL3, and SOD2 were recognized as diagnostic markers for diabetes based on LASSO regression and the support vector machine recursive feature elimination (SVM-RFE) feature selection algorithm. Analysis of immune cell infiltration demonstrated that the four key genes were related to B cells, neutrophils, macrophages, and CD8+ T cells. The diagnostic value of B2M, FTL, and SOD2 for diabetes was higher than that of SH3BGRL3 according to the ROC curve. Validation experiments indicated that the mRNA expression of B2M and FTL was increased in liver tissues of diabetic mice. B2M and FTL can act as diagnostic markers for diabetes and contribute to new understandings of the disease's molecular mechanisms.

Humans↗

Rheumatoid arthritis and pregnancy.

The activity of RA is significantly altered by pregnancy with approximately 70 per cent of patients experiencing substantial improvement in symptoms, signs and sometimes extra-articular manifestations. This lessening of disease activity occurs in association with an almost complete cessation of medications. However, whether partial or complete this remission is short-lived with more than 90 per cent of women who improved relapsing by 6 to 8 months postpartum. Further, in approximately 30 per cent of RA patients the course remains unchanged or worsens during gestation and indeed the first symptoms of RA may develop during pregnancy or shortly thereafter. Conversely active rheumatoid arthritis seems to little influence the maternal course or fetal outcome of pregnancy. The multiple and complex immunologic alterations of the pregnant state are designed to ensure survival of the fetal allograft in a foreign host. A number of these alterations particularly involving modulation of cell-mediated immunity, immunoglobulin composition, immune complex generation, or the inflammatory response have the potential to interfere with the pathophysiology of RA. In short, although the specific mechanism remains an enigma, the reason for the amelioration of RA during pregnancy is probably an incidental and fortuitous reaction to one or more of these immunomodulatory factors.

Anti-Inflammatory Agents↗

Heat-shock protein-based anticancer immunotherapy: an idea whose time has come.

The heat-shock proteins (HSPs) belong to a family of ubiquitous and abundant proteins used successfully in prophylactic and therapeutic vaccination against tumors. The HSPs are natural chaperones of peptides that reflect the immunologic composition of the cell. Immunization with tumor-derived HSP-peptide complexes (HSP-PC) induces a potent antigen-specific immune response against both the primary tumor and preestablished metastases; the response is restricted to the tumor from which the HSPs are purified. This article describes the manufacturing process of an individual HSP vaccine, and discusses the rationale, feasibility, advantages, and safety of this new approach of cancer immunotherapy in the context of various animal models and of the first HSP clinical trial.

Animals↗