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PubMedDate not supplied

Current concepts of tumor immunology. I. Basic immunologic concepts.

Interest in tumor immunology grew out of the study of host response to microbial infections during the second half of the 19th century. However, the growth of interest in transplantation during the 1950s and 1960s is largely responsible for the great surge of scientific investigation into tumor immunobiology which we are experiencing today. Tumor cells possess certain abnormal antigens in addition to their normal complement of transplantation antigens. These abnormal antigens evoke an immune response in the host, which involves both the humoral and the cell-mediated systems. Though the cell-mediated (thymus derived) system is generally conceded the most important role in tumor cell destruction, the humoral (bursal-equivalent derived) system also plays a role in host response which is presently less clearly understood. Certain aspects of the humoral response (blocking factors) actually appear to inhibit the host response against a tumor. This complex system of host immune response to tumor has been termed the immunosurveillance system.

Animals↗
PubMed2000

[Immunology in medical practice. XXIX. Pathogenesis of allergic and immunologic pulmonary diseases].

Recently acquired insights into the complex functions of the immune system in the airways and lungs shed new light on the importance of local immunologic defence mechanisms in the maintenance of a normal lung function. Prolonged exposure to inhaled allergens or to aspecific injurious substances in the environment, in particular, may give rise to the onset of immunopathology that may manifest itself only years later. Clinically, the most common of such diseases is allergic asthma. This results from the interaction of an unknown number of genes with specific and aspecific environmental factors. In chronic obstructive pulmonary disease, exposure to such aspecific factors (cigarette smoking) is the most important aetiological factor. Immune-mediated diseases may also develop in the presence of congenital or acquired immunodeficiencies and in idiopathic diffuse pulmonary disorders. In addition, pulmonary disease is often a component of collagen diseases, occupational diseases and idiopathic pulmonary fibrosis. Recently developed investigational techniques such as bronchoalveolar lavage (BAL), cloning experiments on cells obtained by BAL, and ex vivo studies on cytokine production patterns are making an important contribution to the acquired understanding of the immunopathogenesis of pulmonary diseases.

Acute-Phase Reaction↗
PubMedDate not supplied

The use of three different therapeutic protocols according to the immunologic pathology present in three women with recurrent spontaneous abortion and fetal death for immunologic reasons: flucortolone and salicylates; high-dose intravenous gammaglobulins; subcutaneous heparin.

The authors report three cases of immunologic spontaneous abortions and fetal death. In the first patient there was lupus-like anticoagulant activity with a diagnosis of sub-clinical autoimmune disease; the second showed inadequate blocking factor activity, while the third subject presented excessive lymphocytotoxicity. In these cases three different therapeutic protocols were successfully used: flucortolone and salicylates, high-dose intravenous gammaglobulins and subcutaneous heparin.

Abortion, Habitual↗
PubMed1991

Long-term immunologic tolerance induction in chimeric mice after bone marrow transplantation across major histocompatibility barriers: persistent or redeveloping immunologic responsiveness after prolonged survival.

Employing allogeneic bone marrow chimeras [B6----C3H] (C3H/HeN mice lethally irradiated and then reconstituted with T cell-depleted C57BL/6J bone marrow), we investigated the kinetics of immunological reconstitution and the functional characteristics of the immune system at regular intervals following bone marrow transplantation (BMT). In chimeric mice, almost all spleen cells and peritoneal macrophages showed donor H-2 haplotype within 2 weeks after BMT. The differentiation and maturation of B lymphocytes and macrophages was largely complete by 2 weeks following BMT, whereas T cell functions such as Con A responsiveness and alloreactivity were not restored within 4 weeks. Newly developed T cells were found to be exclusively of donor origin but were tolerant of both donor type and host type major histocompatibility complex (MHC) determinants in assays of mixed lymphocyte reactions and capacity to generate cytotoxic T lymphocytes. Fully allogeneic chimeric mice survived up to one year after bone marrow transplantation without significant reactions or serious diseases. Neither graft-versus-host reaction (GVHR), host-versus-graft reaction (HVGR), nor the wasting diseases described. As compared to age-matched control mice, such fully allogeneic chimeras exhibited one year following BMT somewhat reduced but quite significant plaque forming cell responses to in vitro stimulation with a T-dependent antigen, SRBC. These findings suggest that BMT across MHC barriers may ultimately be useful in humans if all manifestations of GVHR are eliminated by completely removing all T cells from the bone marrow and if all hematopoietic resistance and all aspects of HVGR are eliminated by using sufficient immunosuppression and myeloablation.

Animals↗
PubMed1981

Immunologic consequences of antibiotic-induced abridgement of bacterial infection: effect on generation and loss of protective T cells and level of immunologic memory.

Ampicillin was employed in mice to determine the effect of rapidly abridging bacterial infection on the generation of T cell-mediated antibacterial immunity. It was found that antibiotic-induced abridgement of infection with Listeria monocytogenes had a pronounced effect on the generation of splenic T cells capable of adoptively immunizing normal recipients against a Listeria challenge infection. Ampicillin given at the time of maximum bacterial growth at 24 hr caused a striking reduction in the number of protective T cells produced at the time of peak response on day 6. Although the greatest effect was caused by giving ampicillin early in infection, a significant reduction in peak T cell production occurred even when Ampicillin was given as late as day 5. On the other hand, the effect of abridging infection at the onset of decay of the anti-Listeria response was to cause protective T cells to be lost from the spleen at a much faster rate. These results clearly show that regardless of any immunoregulatory mechanism involved, the duration of generation, and the onset and duration of decay of the anti-Listeria response are determined by the number of replicating Listeria in the tissues. Moreover, Ampicillin-induced abridgement of infection, either before or at the time of peak primary response, resulted in the expression of greatly reduced levels of immunologic memory at a later time. This indicates that memory cells are generated throughout the entire course of the primary anti-Listeria response, including the period of its decay.

Ampicillin↗
PubMed1982

[Immunological mechanisms of specific hyposensitization in allergic diseases of an infectious nature. IV. The comparative characteristics of the changes in the immunological processes in nonspecific (dekaris) and specific (autovaccine) immunotherapy of infectious-allergic bronchial asthma].

The data based on the comparative evaluation of changes in immunological processes due to the effect of decaris, autovaccine and standard staphylococcal allergens are presented. These data indicate that such changes resulting from the clinical effectiveness of different kinds of immunotherapy are accompanied by identical changes in the immune system of patients with infectious allergic bronchial asthma. At the same time the results of this study point out that the therapeutic effectiveness of autovaccine is higher than that of decaris.

Adult↗
PubMed1976

The immunologic system, immunologic deficiency disorders and lymphoid hyperplasia of the small intestine.

The purpose of this paper is to review our current concept of the systems that subserve immunological functions. It concerns specifically the immunodeficiency diseases probably due to a B cell immunodeficiency. An attempt is made to classify those diseases clinically as well as roentgenologically. At last using the enteroclysis technique some examples of immunodeficiency syndromes are shown with special emphasis on developing a malignant disease.

Animals↗
PubMed1986

Immunological consequences of tumor excision: from active immunity to immunological memory.

Excision of the immunogenic Meth-A fibrosarcoma during generation by the host of concomitant antitumor immunity resulted in the appearance in sequence of two qualitatively distinct states of post-excision immunity. Immunity expressed on the day of excision was dependent on Ly-1-2+, cyclophosphamide-sensitive T cells, whereas immunity expressed 2 weeks later was dependent on cyclophosphamide-resistant T cells which can be functionally eliminated by either anti-Ly-1 or anti-Ly-2 monoclonal antibody and complement. The data suggest that antitumor immunity expressed shortly after tumor excision represents active concomitant immunity that is acquired by the host before excision is performed. In contrast, immunity expressed 2 weeks later is based on immunological memory.

Animals↗
PubMed1976

Immunological and non-immunological phagocytosis by inflammatory macrophages, epithelioid cells and macrophage polykaryons from foreign body granulomata.

Inflammatory macrophages, epithelioid cells and macrophage polykaryons were obtained on the surface of round glass coverslips inserted into the subcutaneous tissue of mice and removed at different intervals. About 90 per cent of the macrophages and polykaryons express IgG, C and non-specific surface receptors, involved in phagocytosis, up to 15 days after coverslip implantation. In 21-day-old lesions, about 50 per cent of these cells lose the IgG resed with IgM and complement but do not incorporate these particles and are poorly phagocytic for glutaraldehyde-treated horse red blood cells. The ultrastructural study of these cells demonstrates that they are macrophages which have undergone epithelioid transformation. Whole-body irradiation of mice bearing implanted coverslips of 7 days duration reveals that 6 days after irradiation, the great majority of macrophages and multinucleate cells have acquired epithelioid characteristics. It is suggested that the loss of immunological receptors during epithelioid transformation in granulomas may protect bacteria and be disadvantageous to the host.

Age Factors↗
PubMed1980

The biology, pathology and immunology of a virus induced rat osteosarcoma. II. Immunological studies.

The immunogenicity of a virus-induced rat osteosarcoma was studied utilizing the lymphocyte microcytoxicity test. Lymphocytes from "progressor" animals (in which the tumour progressed and metastasized) demonstrated an ability to kill osteosarcoma cells in vitro, while serum from these animals abrogated or blocked the cell-mediated cytotoxicity. Lymphocytes from "regressor" animals (in which tumours failed to develop or regressed spontaneously) also showed cytolytic activity against osteosarcoma cells in vitro, but their serum failed to block the lymphocyte-mediated cytolysis. Both progressor and regressor animals demonstrated the presence of humoral cytotoxic antibodies to tumour antigens on the basis of the ability of their serum to kill tumour cells in vitro. In an attempt to alter the fatal course of the disease in progressor animals, immunoprophylaxis and immunotherapy of the osteosarcoma in F1 hybrid rats war carried out by injecting them with parentalor, third party, allogeneic lymphoid cells. Injection of parental spleen lymphocytes into F1 hybrids produced a transient graft versus host reaction (GVHR), and prolonged the survival of the animals when lymphocytes were injected three days before, seven days after and on the day of tumour induction. Injection of allogeneic, third party lymphoid cells produced no detectable GVHR and prolonged the survival of F1 hybrids with osteosarcoma only when injected on the day of tumour induction. The prolonged survival of the groups treated with parental lymphoid cells was a result of stimulation of the host's immunological mechanisms during a transient GVHR, whereas the prolongation of survival in the group given allogeneic cells was most likely the result of a direct action of the donor lymphocytes on tumour cells, and not connected to a GVHR.

Animals↗
PubMed1982

Immunological and non-immunological mechanisms involved in adverse reactions to drugs.

This communication reviews the mechanisms involved in anaphylactic and anaphylactoid reactions to intravenous drugs used in anaesthesia. Although the mechanisms involved are pertinent to other drugs and substances used in clinical practice, the use of the intravenous route makes this a particularly worrying problem in anaesthetic practice. Despite the similarity of the clinical manifestations to those expected from immediate immunological hypersensitivity (anaphylaxis), relatively few reactions involve antibodies. Instead, a variety of mechanisms occur where activation of the blood inflammatory response systems, particularly complement, may be either primary or secondary to activation of the coagulation or fibrinolytic cascades of the blood clotting mechanisms. Immediate anaphylactoid reactions, manifest in the release of vasoactive substances such as histamine, may therefore pose very minor problems compared with coagulation problems arising in the peri- and post-operative period. It is important to discover the mechanism of all adverse reactions not only if these are to be avoided in the reactants in the future but also because of the necessity for devising suitable prophylactic and therapeutic measures for general use. The practical problems of such investigations are explored with particular reference to the laboratory investigation of subclinical reactions in terms of plasma histamine release and changes in blood leucocyte distribution.

Adult↗
PubMed1984

Local histamine release after immunological and non-immunological mast cell degranulation in vivo.

Plasma histamine concentration in the circulation has been proposed as an index of mast cell degranulation occurring in vivo but there are problems with this approach in practice. Local elevations in plasma histamine occur in blood draining the site of antigen challenge in forearm skin. We have compared changes in plasma histamine concentration with time following intradermal injection of antigen, codeine or histamine to produce matched wheal and flare responses in 4 atopic subjects. Less histamine appears to be released after non-immunological challenge.

Adult↗
PubMed1978

Immunological properties of membrane-bound adenosine triphosphatase: immunological identification of rutamycin-sensitive F0.F1ATPase from Micrococcus luteus ATCC 4698 established by crossed immunoelectrophoresis.

(1) F0.F1ATPase (EC 3.6.1.3) from Micrococcus luteus ATCC 4698 was solubilized from plasma membranes by the non-ionic detergent Triton X-100 in the presence of 0.05 M MgCl2. (2) The antibiotics rutamycin, Dio-9, quercetin, oligomycin, botrycidin, efrapeptin, leucinostatin, valinomycin, and venturicidin as well as N,N'-dicyclohexylcarbodiimide and dinitrophenol are potent inhibitors of F0.F1ATPase activity.(3) F0.F1ATPase activity is completely inhibited by anti-F1ATPase antibodies. The inhibition is non-competitive. (4) Crossed immunoelectrophoresis reveals a reaction of immunological identity of F0.F1ATPase and F1ATPase indicating that both enzymes have in common antigenic sites.

Adenosine Triphosphatases↗
PubMed2006

Immunological synapse arrays: patterned protein surfaces that modulate immunological synapse structure formation in T cells.

T cells are activated by recognition of foreign peptides displayed on the surface of antigen presenting cells (APCs), an event that triggers assembly of a complex microscale structure at the T cell-APC interface known as the immunological synapse (IS). It remains unresolved whether the unique physical structure of the synapse itself impacts the functional response of T cells, independent of the quantity and quality of ligands encountered by the T cell. As a first step toward addressing this question, we created multicomponent protein surfaces presenting lithographically defined patterns of tethered T cell receptor (TCR) ligands (anti-CD3 "activation sites") surrounded by a field of tethered intercellular adhesion molecule-1 (ICAM-1), as a model substrate on which T cells could be seeded to mimic T cell-APC interactions. CD4(+) T cells seeded on these surfaces polarized and migrated; on contact with activation sites, T cells assembled an IS with a structure modulated by the physical pattern of ligand encountered. On surfaces patterned with focal spots of TCR ligand, T cells stably interacted with activation sites, proliferated, and secreted cytokines. In contrast, T cells interacting with activation sites patterned to preclude centralized clustering of TCR ligand failed to form stable contacts with activation sites, exhibited aberrant PKC- clustering in a fraction of cells, and had significantly reduced production of IFN-gamma. These results suggest that focal clustering of TCR ligand characteristic of the "mature" IS may be required under some conditions for full T cell activation.

Animals↗
PubMed1991

Mediator secretion from human skin mast cells provoked by immunological and non-immunological stimulation.

Mast cells of the human skin not only release mediators following immunological activation, but may also be stimulated to release histamine by the neuropeptides substance P, vasoactive intestinal polypeptide and somatostatin or by other basic secretagogues such as morphine, poly-L-lysine and compound 48/80. Release of histamine under these conditions is rapid and accompanied by minimal generation of the eicosanoids, prostaglandin (PG)D2 and leukotriene (LT)C4. Transient elevations of intracellular calcium are associated with mediator secretion induced by both stimuli, that induced by anti-IgE being derived from extracellular sources through channels in the plasma membrane while that stimulated by neuropeptides is mobilized intracellularly. Similarly, elevations of intracellular cyclic adenosine monophosphate (AMP) induced by anti-IgE occur only in the presence of extracellular calcium whereas with substance P elevations are apparent even in the absence of extracellular calcium. With the latter stimulus, histamine release is complete before the peak cyclic AMP is achieved. Histamine release stimulated by both secretagogues is unaffected by sodium cromoglycate or nedocromil sodium but is reduced by both salbutamol and isobutylmethylxanthine. Despite these biochemical and temporal differences, degranulation induced by both secretagogues proceeds by compound exocytosis which is indistinguishable under the electron microscope.

Calcium↗
PubMed1976

Secretory immunological system of fowl. V. The gallbladder: an integral part of the secretory immunological system of fowl.

The concentrations of IgA, IgM and IgY were measured in gallbladder (GB) bile and serum from chickens of various ages. The ontogeny data suggested that IgA and IgY were synthesized by the GB. Furthermore, the chicken GB becomes lymphoid 3-8 days post-hatch and contains distinct foci of lymphocytes by 7 weeks of age. That the GB can synthesize and secrete IgA was shown in two ways. IgA-containing cells were demonstrated by immunofluorescence and in vitro studies with adult GB explants showed the synthesis and secretion of IgA and also IgY and IgM. Immunoglobulin class suppression experiments and quantitation of IgA in sera from selected sites supported the concept of synthesis and secretion of IgA by the GB. Several lines of evidence also support the concept of some bile IgA being derived from serum. Introduction of antigen directly into the GB was shown to stimulate antibody formation, and this antibody was detectable in bile and serum. A very unusual finding, in one animal, was the presence of a normal secretory IgA concentration in the presence of undetectable serum IgA. These data indicate that the GB is an integral part of the secretory immunological system and suggest that aberrations in GB-immune function may result in pathological clinical manifestations.

Aging↗
PubMed1975

[Tissue immunology in psoriasis. I. Changes in the immunologic mechanism caused by methotrexate].

To evaluate the posibility of detecting immunological alterations in psoriasics after MTX's treatment, lymphocyte culture was used, following Nowell's techniqe with slight modifications. There were no significant differences in blastic response between psoriasic patients and normals. Important variations were not observed in blastogenesis, after three and six weeks of MTX'S treatment, in the group of patients without previous medication. Another group of patients, selected for their therapeutic resistence to the drug employed, was also studied. There were no significant differences between the group sensitive to medication and the control. The values obtained suffered no modification, when treatment was continued, in similar doses, at three and six weeks of starting it. Finally, no alterations were found in the blastic response of those patients who had complete remission of psoriasis, after having been under MTX at least, six months before our work began.

Adult↗
PubMedDate not supplied

Immunological basis for the use of TNFalpha-blocking agents in ankylosing spondylitis and immunological changes during treatment.

TNFalpha is expressed in high amounts at the site of inflammation in ankylosing spondylitis, which provided the basis to initiate treatment studies with TNF-blocking agents. We could show that the immunological effects of infliximab and etanercept differ in patients with AS, although the clinical effect was similarly good. While infliximab induced a downregulation of the production of the T-helper 1-cytokines IFNgamma and TNFalpha, etanercept treatment triggered rather an upregulation of these cytokines secreted by T cells after in vitro stimulation.

Antibodies, Monoclonal↗