[Generalities on immune response. Humoral immunity, cellular immunity, cell interactions, complement. Study in clinical practice].
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Animals↗
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Bone marrow transplantation in children with severe aplastic anemia: reconstitution of cellular immunity.
Cellular immune functions were evaluated longitudinally in seven children with severe aplastic anemia, who were successfully transplanted with bone marrow cells from an HLA-identical, mixed lymphocyte culture (MLC)-negative sibling. Several parameters were followed: the number of lymphocytes and E rosette-forming cells in the peripheral blood and the lymphocyte reactivity toward various mitogens, antigens, and allogeneic lymphocytes. Some patients already displayed decreased in vitro lymphocyte reactivity before transplantation, especially with regard to the response to pokeweed mitogen (PWM). After transplantation, a severe cellular immunodeficiency developed in all patients, with low numbers of T cells and markedly impaired responsiveness to mitogens, antigens, and allogeneic lymphocytes. Variations between patients were substantial, both with regard to the severity and duration of the immunodeficiency and to the pattern of the recovery of lymphocyte responses to mitogens and antigens. This variability might be attributable to an imbalanced proliferation of different lymphocyte subsets and/or the sequence of appearance of receptors for mitogens on the cell surface.
Anemia, Aplastic↗
Amino acid dimorphism and parasite immune evasion: cellular immune responses to a promiscuous epitope of Plasmodium falciparum merozoite surface protein 1 displaying dimorphic amino acid polymorphism are highly constrained.
Like most other surface-exposed antigens of Plasmodium falciparum, the leading malaria vaccine candidate merozoite surface protein (MSP)-1 contains a large number of dimorphic amino acid positions. This type of diversity is presumed to be associated with parasite immune evasion and represents one major obstacle to malaria subunit vaccine development. To understand the precise role of antigen dimorphism in immune evasion, we have analyzed the flexibility of CD4 T cell immune responses against a semi-conserved sequence stretch of the N-terminal block of MSP-1. While this sequence contains overlapping promiscuous T cell epitopes and is a target for growth inhibitory antibodies, three dimorphic amino acid positions may limit its suitability as component of a multi-epitope malaria vaccine. We have analyzed the CD4 T cell responses in a group of human volunteers immunized with a synthetic malaria peptide vaccine containing a single MSP-143-53 sequence variant. All human T cell lines and HLA-DR- or -DP-restricted T cell clones studied were exclusively specific for the sequence variant used for immunization. Competition peptide binding assays with affinity-purified HLA-DR molecules indicated that dimorphism does not primarily affect HLA binding. Modeling studies of the dominant restricting HLA-DRB1*0801 molecule showed that the dimorphic amino acids represent potential TCR contact residues. Lack of productive triggering of the TCR by MHC/variant peptide ligand complexes thus seems to be the characteristic feature of parasite immune evasion associated with antigen dimorphism.
Amino Acid Sequence↗
Streptococcal preparation as an activator of host-mediated immune response: cellular immunity and alternate pathway of complement.
Streptococcal preparation, OK-432, was examined for its ability to initiate a host-mediated immune response. Aged individuals with negative skin response to phytohemagglutinin (PHA), as well as reduced in vitro blastoid transformation of lymphocytes, were treated with OK-432, and the response to PHA appeared in two out of three cases. The preparation was also demonstrated to convert C3 proactivator of complement when incubated with fresh human serum, as tested by immunoelectrophoresis, indicating the possibility that OK-432 might activate the alternate pathway of complement.
Aged↗
[Inflammatory polyradiculoneuritis and cellular immunity: study of the cellular immune response towards peripheral nerve antigens by the leukocyte migration test].
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Cell Migration Inhibition↗
Immune cellular response to HPV: current concepts.
Although cellular immunity is essential for the elimination of human papillomavirus (HPV), the mechanisms involved are still poorly understood. We summarize the main mechanisms involved in cellular immune response to infections caused by HPV. Immunotherapies for HPV-related cancers require the disruption of T-cell response control mechanisms, associated with the stimulation of the Th1 cytokine response.
Antigen-Presenting Cells↗
[Cellular immunity in rheumatoid arthritis - cellular immunity seen in MIT and lymphoblast formation and specificity of the antigen].
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Arthritis, Rheumatoid↗
Cellular immunity in congestive cardiomyopathy. The normal cellular immune response.
In vivo and in vitro tests of cellular immunity were studied in patients with congestive cardiomyopathy to determine whether these patients have normal or depressed cell mediated immunity to common environmental antigens and mitogens. No abnormality was found, but this does not exclude the possibility that transient depression of cell mediated mechanisms occurs early in the illness before clinical presentation.
Cardiomyopathy, Dilated↗
Heterologous prime-boost vaccination strategies for HIV-1: augmenting cellular immune responses.
Cellular immune responses, specifically those mediated by CD8+ cytotoxic T-lymphocytes and CD4+ helper T-lymphocytes, are needed to control HIV-1 in vivo and to mediate viral clearance. Vaccines capable of inducing cellular immune responses are, therefore, widely considered as necessary for controlling the spread of HIV-1. Numerous different vaccine delivery formats designed to induce cellular immune responses have been evaluated in animal models and clinical trials. These include adjuvant-supplemented peptide- or protein-based formulations, DNA vaccines and viral vectors. While none of the current generation vaccine delivery technologies have proved potent enough for stand-alone use against HIV-1-infection, mixed delivery vaccine formats, vaccination schemes known as heterologous prime-boost, have proved to be significantly potent methods for inducing cellular immune responses. Different forms of heterologous prime-boost vaccines are currently being tested in numerous clinical trials and hold significant promise.
AIDS Vaccines↗
The effect of clofibrate and pyridinol carbamate on the circulating immune complexes and cellular immune response in experimental atherosclerosis.
Cholesterol-fed rabbits were treated with clofibrate, pyridinol carbamate and with both drugs simultaneously. The quantity of circulating immune complexes in the sera of the animals was measured weekly and the migration inhibition test was carried out in the 12th week of the experiment. The trend of the changes in the concentration of the immune complexes was rather similar to that of the cellular immune response. Compared with the values obtained in the control animals, in the cholesterol-fed group a markedly higher level of immune complexes and a significant migration inhibition could be detected. The administration of clofibrate or pyridinol carbamate alone had no effect on the concentration of immune complexes. Pyridinol carbamate did not influence the migration inhibition; however, it became similar to the healthy controls in the clofibrate-treated group. Simultaneous treatment with both drugs resulted in a decrease in the quantity of immune complexes and a diminution of the migration inhibition.
Animals↗
Cytomegalovirus-specific immune response and the cellular immune status of malignant lymphoma.
Cytomegalovirus (CMV)-specific immune responses and the general cellular immune status of 24 untreated patients with Hodgkin's disease (HD) and 22 with non-Hodgkin lymphoma (NHL) were evaluated in comparison with matched controls. The incidence of antibodies against CMV-induced early (EA) or late (LA) antigens was not different between patients and controls. LA antibody titres were markedly lower in the lymphoma patients (p = 0.01), especially in the NHL subgroup (p = 0.008), but not in HD patients. EA antibody titre levels were not significantly different between patients and controls. CMV-specific lymphocyte reactivity (LR) was impaired in LA seropositive--and even more so in EA seropositive--lymphoma patients. General cellular immunity tested with LR to mitogens and an antigen cocktail was more disturbed in HD patients (only PWM-LR normal) than in NHL patients (only Con A-LR disturbed). The percentage of circulating T lymphocytes was markedly lowered (less than 60%) in only 2 HD and 4 NHL patients. The impairment of CMV-LR was not directly related to the general cellular immune status of the patients. It appeared furthermore to be virus-specific when it was compared with LR to Epstein-Barr virus antigen. The impairment of CMV-specific immunity in lymphoma patients probably reflects a defect of the immunological defence against endogenous CMV. This defect apparently, occurs early in the course of illness before the general cellular immune status has deteriorated and it may have a pathogenetic significance for lymphoid malignancies.
Adolescent↗
Altered cellular immunity and suppressor cell activity in patients with primary retinitis pigmentosa.
A group of 54 patients with primary retinitis pigmentosa were studied and the following findings are described: response of lymphocytes to stimulation by phytohaemagglutinin (PHA); response of lymphocytes to stimulation by xenogenic retinal extract; distribution of T and T-active lymphoid populations; total suppressor activity induced by concanavalin-A (con-A). The results obtained showed a reduction in the response to PHA (p less than 0.05), a positive response of 26/45 (p less than 0.001) to stimulation by retinal extract, a reduction in the T and T-active lymphoid populations (p less than 0.01), (p less than 0.01), and a diminished total suppressor activity induced by con-A (p less than 0.01). This alterations of immune cellular responses and the diminished suppressor activity in the group of patients, in comparison with a control group of healthy subjects, seems to indicate the existence of an immune process of disregulation (autoimmunity?) in the pathology of primary retinitis pigmentosa.
Adult↗
Recombinant HIV structural proteins detect specific cellular immunity in vitro in infected individuals.
Peripheral blood mononuclear cell (PBMC) cultures were established from patients with antibody to human immunodeficiency virus (HIV). Asymptomatically infected patients [5 of 19] had significant lymphocyte transformation responses induced in culture by a purified, recombinant envelope glycoprotein (rgp120) from the virus. A few (4 of 55) subjects with AIDS related complex (ARC) and no subjects with AIDS (0 of 29) had proliferative responses to this protein. These responses correlated directly with circulating levels of helper/inducer lymphocytes (p less than .01) and indirectly with virus antigen in blood (p = .04). Also, these responses occurred significantly less frequently than responses to herpes simplex virus (HSV) or cytomegalovirus (CMV) antigens in seropositive ARC patients (p less than .005). These data indicate that the frequency of immune cellular responses to rgp120 decline in association with disease progression, and become undetectable in frank AIDS. As rgp120-induced proliferation was not observed in cells from 15 seronegative immunocompetent subjects, this response appears immune specific. Immune T-lymphocyte-mediated responses to this HIV envelope glycoprotein may allow the prediction of future clinical events and may be useful in monitoring immune-enhancing therapy in patients with ARC and AIDS.
AIDS-Related Complex↗
The effects of 13-cis-retinoic acid and beta-carotene on cellular immunity in humans.
Deficiency of vitamin A and/or its precursors has been associated with increased cancer risk in animals and humans. Therapeutic trials of vitamin A and related compounds have demonstrated activity in several cancerous and precancerous conditions. The authors measured the effects of a retinoid, 13-cis-retinoic acid, and a carotenoid, beta-carotene, on the human immune system in vivo in conjunction with their use in ongoing clinical trials. Immune cell subpopulations were analyzed by quantifying the expression of markers using flow cytometric study. Both compounds produced significant effects on immune cell populations. 13-cis-Retinoic acid resulted in an increase in the percentage of peripheral blood lymphoid cells expressing surface markers for T-helper cells with only minimal effect on natural killer cell marker expression. In contrast, beta-carotene produced an increase in the percentage of cells expressing natural killer cell markers with smaller effect on T-helper markers. Modest increases in the percentage of cells expressing Ia antigen, transferrin, and interleukin-2 receptors were produced by both drugs. These results suggest that retinoids and carotenoids can produce major changes in immune cellular marker expression in vivo in humans at doses relevant to their potential clinical use.
Adult↗
Antigen recognition and the immune response. Humoral and cellular immune responses to small mono- and bifunctional antigen molecules.
L-Tyrosine azobenzene-p-arsonate (RAT) induced cellular immunity without antibody production in guinea pigs. Bifunctional antigens were prepared consisting of one RAT carrier moiety linked either directly to a dinitrophenyl (DNP) haptenic determinant or through one or more 6-amino-caproyl (SAC) spacers. Each SAC unit has an extended span of 8 A. Guinea pigs immunized with these conjugates developed cellular immunity directed against the RAT determinant and antibody specific for the DNP determinant. The anti-DNP response was the same with one or three SAC spacers, but was significantly weaker when the two determinants were joined without a spacer. Animals immunized with either DNP-SAC-TYR or DNP-TYR developed neither cellular nor humoral immunity. Prior immunization with RAT potentiated the secondary anti-hapten response to DNP-SAC-RAT. Modification of RAT at either the arsonate or tyrosine positions showed that other charged groups (sulfonate and trimethylammonium) could substitute for arsonate without loss of immunogenicity. Removal of either the amino or carboxyl group from the side chain of tyrosine did not abolish immunogenicity, but immunogenicity was lost upon removal of both. Immunization with symmetrical bifunctional RAT-(SAC)(n)-RAT and cyclo-(L-RAT-D-RAT) antigens led to cellular immunity but no anti-arsonate antibody, suggesting a barrier to "self-help." These compounds were also ineffective in inducing a secondary anti-arsonate response in animals primed with arsonate-BSA conjugates and RAT.
Animals↗
Cord blood leucocyte expression of functionally significant molecules involved in the regulation of cellular immunity.
The cellular immune system of the newborn infant is immature and hypo-responsive when compared with adults. The extent to which immaturity of the leucocyte function underlies hyporesponsiveness in the newborn is incompletely understood. In this study flow cytometric techniques were applied to investigate the concurrent expression of a range of surface and intracellular leucocyte functional molecules and cytokines in resting and stimulated cord and adult blood. Production of interleukin (IL)-2 and expression of the components of its receptor, IL-2R alpha/beta/gamma, were investigated. No differences in the proportion of leucocytes producing IL-2R alpha and IL-2R gamma were observed for newborns and adults. A lower proportion of T cells and natural killer (NK) cells from newborns expressed IL-2R beta and upregulation of expression was slower. We hypothesize that reduced IL-2R beta may curtail early autocrine IL-2 activation of immune responses in the newborn. This hypothesis was supported by the observation that an increased proportion of stimulated T cells from newborns produced IL-2 at 4 h poststimulation, but at 24 h the proportion was lower than for adult T cells. The very low levels of interferon (IFN)-gamma produced by neonatal T cells and NK cells may also be partly explained by a curtailment of early autocrine activation of T cells. Expression and kinetics of upregulation for other functional molecules were studied. CD71, HLA-DR, tissue factor and CD152 levels were not significantly different for adults and newborns, suggesting that cord blood leucocytes, in some respects, may demonstrate functional maturity. IL-6 secretion by stimulated monocytes was also comparable in cord and adult blood. However, IL-1 alpha and IL-1 beta were produced by a lower proportion of monocytes from newborns than adults. Similarly, tumour necrosis factor (TNF)-alpha production for monocytes and T cells was lower in cord blood. The mean fluorescence intensity for IL-1 alpha, IL-1 beta and TNF-alpha was also lower for leucocytes from cord blood. These findings are significant in relation to the inability of newborn infants to mount a febrile response to infection. The findings of lower expression of IL-2R beta and lower production of inflammatory cytokines IL-1 alpha, IL-1 beta and TNF-alpha is a basis for improved understanding of the immunological immaturity of leucocytes in the newborn.
Adult↗
Haemodialysis, continuous ambulatory peritoneal dialysis and cellular immunity.
The cellular immunity of haemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients was studied with regards to T-lymphocyte subsets and to suppressor T-cell function. The two groups of patients showed similar alterations: low proportions of suppressor-cytotoxic T-cells and low suppressive activity. In both groups there is a deterioration of this suppressive activity with time on dialysis.
Aged↗
Aging: the cellular immune response against autologous and foreign antigens is affected before the humoral response.
In this study we examined the auto- and hetero-immune response in mice of different ages immunized with antigens of Trypanosoma cruzi (S-105). We observed that 20-day- and 12-month-old mice showed decreased response to foreign antigens and increased response to autoantigens, compared with 3-month-old immunized mice. The 6-month-old mice showed hetero- and auto-immune cellular responses similar to those of 12-month-old animals; however, the humoral response was similar to that of 3-month-old animals against either antigen, suggesting that the compartments of the immune response are altered at different moments in the same individual. Immune response against a foreign antigen is correlated with the presence of cellular infiltrate in skeletal and heart muscle whereas no modifications in the tissue are noticed in animals with an autoimmune response. Also, we observed from cell transfer experiments that lymph node cells are involved in the dysregulation that we noticed with aging.
Aging↗