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Severe feed restriction enhances innate immunity but suppresses cellular immunity in chicken lines divergently selected for antibody responses.

The main aim of this study was to investigate the effects of different levels of feed restriction (FR) on immune responses of chicken lines divergently selected for high (H) and low (L) antibody responses to SRBC. We hypothesized that severe feed restriction suppresses immune responses and the level of immune suppression differs between birds with different genetic background. Therefore, we tested antibody responses, blood lymphocyte proliferative responses, and production of reactive oxygen intermediates (ROI) by Zymosan A-stimulated blood cells in chicken lines maintained on 3 levels of FR. The H line birds had significantly higher antibody responses, higher ROI production, and lower corticosterone (CORT) levels when compared with the L line birds. Feed restriction induced no significant effect on specific antibody responses to either a T helper 1- (Mycobacterium butyricum) or a T helper 2- (keyhole limpet hemocyanin) type antigen. Feed-restricted birds showed a marked reduction in natural antibodies binding lipoteichoic acid, in vitro lymphocyte proliferation in response to stimulation with concanavalin A, BW gain, and relative lymphoid organ weights compared with the birds fed ad libitum. However, FR birds showed a markedly enhanced ROI production, and plasma CORT levels compared with the birds fed ad libitum. The enhanced ROI production and suppressed lymphocyte proliferation coinciding with enhanced plasma CORT levels suggest stress-mediated immunomodulating effects of FR. A significant treatment by line interaction was found for ROI production; the increase of ROI production was larger in the H line than in the L line under severe FR. The increase in CORT levels was larger in the L line than in the H line under severe FR. Furthermore, the L line gained more BW than the H line under ad libitum conditions. Finally, under severe FR, relative spleen weight was lower in the L line than in the H line. The present findings suggest genetic differences affecting physiological and immunological responses under FR conditions.

Animals↗

[Studies on the mechanism of the protective immunity against Schistosoma japonicum--cellular immune responses].

Kinetics of cellular immune responses was studied in C57BL/6 mice immunized with irradiation-attenuated vaccine, cryopreserved and irradiated vaccine or frozen-thawn vaccine. The results and analysis of correlation between cellular responses and resistance showed that cellular immune responses played an important role in the protective immunity against Schistosoma japonicum.

Animals↗

RNA-mediated transfer of cellular immunity to a synthetic env antigen of the human immunodeficiency virus (HIV-1).

A sheep was immunized with a synthetic peptide corresponding to amino acid residues 586-606 of the precursor envelope protein GP-160 of the HIV-1 including a conserved epitope region of the GP-41 transmembrane protein in the mature viral particles, referred to as SM 284 HIV-1 [1]. It is demonstrated that immune RNA extracted from the lymphoid organs of the immunized animal (SM 284 HIV-1 I-RNA) was able to transfer immune cellular reactivity to SM 284 HIV-1 in vitro to human and rabbit lymphocytes and in vivo to Cebus apella monkeys. The transfer was detected by the leukocyte adherence inhibition test (LAI) as an indicator of cellular reactivity. One of the most relevant results was the demonstration that SM 284 HIV-1 I-RNA was able to induce cellular immunological memory in vivo in monkeys. These results may be relevant to delineate a new alternative for immunomodulation against HIV infection.

Amino Acid Sequence↗

Cellular immune reactivity to recombinant OspA and flagellin from Borrelia burgdorferi in patients with Lyme borreliosis. Complexity of humoral and cellular immune responses.

Patients with Lyme borreliosis (LB) usually develop a vigorous T cell response against the causative pathogen Borrelia burgdorferi, but little is known about the antigens recognized in the cellular response. Therefore, T cell reactivities against whole bacteria, recombinant 31-kD (outer surface protein A, [OspA]), and 41-kD proteins (flagellin) from B. burgdorferi were studied in patients with LB, non-LB patients, and healthy donors. In parallel, specific antibodies were determined by Western blot analysis. Virtually all patients with LB exhibited marked cellular responses to whole B. burgdorferi, which were significantly elevated compared with the control groups in both early and late disease stages. However, analyses using the purified antigens OspA and flagellin revealed considerable heterogeneity in the cellular reactivities among individuals as well as variations during the course of infection. T cell responses to OspA were significantly increased in patients with early LB compared with both control groups whereas in late-stage disease responses only exceeded those of non-LB patients and were not different from normal donors. Cellular immune reactivities to flagellin were significantly higher only in early LB compared with both control groups. Reciprocally, several control subjects demonstrated marked cellular responses to OspA and flagellin, suggesting that reactions to these proteins may not always be related to LB. T cell reactivity did not correlate well with the presence of specific antibodies. Almost all seropositive patients in both early and late stage LB had serum antibodies against flagellin, but antibodies to OspA were detectable only in a subset of late LB sera. These data demonstrate the complexity of the humoral and the cellular immune responses to components of B. burgdorferi.

Adolescent↗

Hepatitis C virus envelope DNA-based immunization elicits humoral and cellular immune responses.

The vaccine development for hepatitis C virus (HCV) is highly urgent to prevent non A and non B hepatitis. It was recently shown that the HCV envelope proteins appeared to the key viral antigens to induce protective immunity. To generate immune responses to the HCV envelope proteins on the DNA-based immunization, various envelope gene-containing plasmids were constructed. For efficient expression and secretion of envelope proteins, the signal sequence of each envelope protein was replaced with either herpes simplex virus type-1 (HSV-1) gD or signal sequence of gD and truncated C-terminal hydrophobic regions of envelope proteins. The intramuscular injection of these plasmids generated a significant level of antibody titers to the E1 and E2 proteins, which maximally reached 850 and 25,000 respectively. The secreted form of each envelope protein and the fusion of the highly immunogenic gD proteins were shown to have no significant effect on generating immune responses to the envelope proteins. In addition, immunized rats appeared to generate antibodies directed to the homologous HVR-1 peptide. Splenic lymphocytes from immunized rats were shown to induce significant T-cell proliferative responses with the stimulation of recombinant E1 and E2 proteins. Our results demonstrated that the HCV envelope-DNA based immunization could elicit both humoral and cellular immune responses.

Amino Acid Sequence↗

The role of asymmetry of nervous and immune systems in the formation of cellular immunity of (CBaxC57Bl/6) F1 mice.

We have previously shown the existence of functional asymmetry of the immune system and the role of brain hemispheres and different lobes of thymus in the development of humoral immune response in (CBA x C57Bl/6) F1 mice. The role of asymmetry of the nervous and immune systems in the formation of the cellular immune response [delayed-type hypersensitivity (DTH) reaction] in these mice has been studied in our work. In order to test the influence of asymmetry of the primary immune organs, thymus, on the cellular immune response, mice were thymectomized and then we studied the effect of the injection of cells from contralateral thymus lobes of right-dominant and left-dominant donors by motor asymmetry on how pronounced the DTH reaction in the back left paw was. The injection of thymocytes from right-dominant donors appeared to result in significant differences in DTH reaction between left- and right-handed mice. At the same time, our experiments failed to discover any pronounced role of thymus asymmetry in the formation of DTH reaction. In order to test the influence of asymmetry of peripheral immune organs, regional lymph nodes, on the regulation of cellular immune response, we compared the DTH reaction in left and right paws of mice. We found that the intensity of the DTH reaction to sheep red blood cells in the front paws of (CBA x C57Bl/6) F1 mice depends not only on whether the antigen is injected into the left or right paw but also on the motor asymmetry of the hemispheres. While comparing the DTH reaction in the back left and right paw of mice we showed that in both right- and left-handed mice it was much more pronounced in the left paw than in the right one. The data obtained testify to the functional asymmetry of bilateral lymph nodes located near the forming cellular immune reaction. Thus, the results obtained show that the intensity of DTH reaction in (CBA x C57Bl/6) F1 mice depends on the functional asymmetry of regional lymph nodes and motor of brain hemispheres. The thymus functional asymmetry is of slight importance in DTH reaction.

Animals↗

Adaptive immunity in teleosts: cellular immunity.

Specific cell-mediated immunity in fish is to date a relatively poorly studied area in fish immunology. Despite breakthroughs in the cloning of the fish TcR and major histocompatibility (MHC) molecules, and more recently the CD3 and CD8 marker molecules, assays to measure specific T-cell responses are still in their infancy. The classical division of T cells into cytotoxic (Tc) and helper (Th) subpopulations is probably relevant to fish, based on the presence of these functional activities and MHC class I and II molecules, but as yet even this is not definitively proved. This review will consider which specific cell-mediated responses can be measured within fish and what their relevance is to fish vaccination programmes.

Amino Acid Sequence↗

Assays of cellular immunity.

Numerous cellular assays are available to study the response or activities of mononuclear and polymorphonuclear cells in domestic species. When the assays, most developed originally to study rodent or human cells, are adapted to the cells of domestic species, minor or major modifications have been necessary. Furthermore, interpretation of results of the assays with cells from domestic species are not always consistent with those obtained in the original system, and it should not be expected that the assays will always provide results that can be interpreted similarly among species. Application and additional experience with these techniques, as well as new techniques, will provide a foundation for our understanding of the importance of cellular mechanisms in immunity of domestic species.

Animals↗

Cellular immune responses to influenza.

Cellular immune responses are believed to play an important role in controlling influenza infection. CD4+ and CD8+ T cell responses are well described and CD8+ immunity is of paramount importance in killing virally infected cells. In the past few years several novel techniques have been devised which allow quantification of antigen-specific cellular immune responses and these will be reviewed briefly. Influenza-specific cellular immunity is elicited following natural infection and several viral proteins have been identified as targets for cellular responses. Cellular immunity is detectable throughout life in most donors but there is clear evidence of impaired cellular immunity in the elderly, a population at particular risk of influenza infection. This finding must be viewed against the background of 'immune senescence' that is documented with aging. Cellular responses are able to provide heterosubtypic immunity to influenza viral antigens. As such the induction of cellular immune responses is a highly desirable aim of vaccination protocols. Induction of cellular immunity with conventional formalin-inactivated vaccine is poor although some improvement may be derived from novel forms of vaccine delivery such as the use of adjuvanted carriers. Nevertheless, a range of new vaccines is being developed which are more effective in priming cellular responses. Although there is relatively little detail on the nature of the cellular response induced by these agents, they hold out the promise of more effective and durable protection from influenza infection.

Adjuvants, Immunologic↗

Bacterial modulation of the cellular immune response in mice. II. Stimulation by endotoxin of the reduced cellular immune response to LCM virus infection in aged mice.

Aging mice treated with radio-detoxified endotoxin and subsequently inoculated intracerebrally with lymphocytic choriomeningitis (LCM) virus died earlier and in a higher rate than the virus infected and otherwise untreated controls. Thus, in mice with insufficient T lymphocyte function due to aging, the radio-detoxified endotoxin pretreatment contributed to the outcome of LCM virus infection in the form of lethal meningitis. That indicates a stimulatory effect on the reduced cellular immunological reaction to the virus infection.

Age Factors↗

Estradiol-induced alteration in the immune system. II. Suppression of cellular immunity in the rat is not the result of direct estrogenic action.

Estradiol has been reported to suppress numerous cellular immune response. What is not known is how estradiol exerts this effect. In vivo administration of estradiol to male rats caused time-related immunomodulatory effects leading to enhancement of lymphocyte transformation while suppressing a mixed lymphocyte reaction (MLR) response. The suppression of the MLR response was not due to alterations in the ratio of helper and suppressor T cells, nor was it due to alterations in either cell viability or the number of cells in culture. Lymphocytes cultured in vitro with estradiol, however, fail to show any alteration in the responsiveness in either MLR or lymphocyte transformation assays. The suppressive effects of estradiol cannot be transferred from a primary MLR culture to a second MLR culture using the supernatants from the primary MLR culture. Lymphocytes from animals given estradiol in vivo show no alteration in the production of interleukin 2: added in vitro to primary MLR cultures, Interleukin 2 failed to restore full responsiveness to lymphocytes from animals treated in vivo with estradiol. These results suggest that estradiol acts indirectly to cause an alteration in the responsiveness of the regulatory cells of the cellular immune system.

Animals↗

Cellular immune responses to recombinant antigens in pregnant women chronically infected with Toxoplasma gondii.

The parasite Toxoplasma gondii can infect most mammals and birds, sometimes causing severe pathology. Primary infection during pregnancy can result in abortion or fetal defects. Host immunity, particularly cellular immunity towards antigenic peptides, can control infection, but an efficient vaccine is not yet available. We have evaluated T-cell responses to a crude soluble toxoplasma antigen (ST-Ag) and to five recombinant peptide antigens of cells in whole-blood cultures from 22 pregnant women with preexisting infections and from 7 pregnant negative controls. Cells from all infected patients but from none of the controls responded specifically to ST-Ag by expressing surface CD25 on culture. Responses to the recombinant antigens showed considerable variation between individuals. rGRA1 elicited a response in 16 of the 22 samples (73%), rSAG1 in 13, rGRA7 in 9, rGRA6-CT in 4, and rGRA6-NT in only 1. Most responding cells were CD4(+). Cells from infected subjects cultured with ST-Ag all released high levels of gamma interferon (IFN-gamma) into the culture supernatant (4,343 +/- 2,536 pg/ml). Cells from 12 patients released IFN-gamma after culture with rGRA1 (130 +/- 98 pg/ml), those from 10 patients released it after culture with rSAG1 (183 +/- 128 pg/ml), and those from 4 patients released it after culture with rGRA7 (324 +/- 374 pg/ml). Intensity of IFN-gamma production in response to the latter two recombinant antigens correlated with responses to ST-Ag (r = 0.61 and 0.53, respectively; P < 0.01). Interleukin-4 was always absent from supernatants of cells stimulated with toxoplasma antigens. The heterogeneity of human responses to individual recombinant toxoplasma antigens should be considered in the design of potential vaccines.

Animals↗

Humoral and cellular immune response of adults from northeastern Brazil with chronic Trypanosoma cruzi infection: depressed cellular immune response to T. cruzi antigen among Chagas' disease patients with symptomatic versus indeterminate infection.

Infection with Trypanosoma cruzi can cause chronic Chagas' disease manifestations (cardiac, gastrointestinal), although most persons with chronic infection have no ill effects (indeterminate form). Cell-mediated immunity (CMI) responses are believed to be intrinsically important in the containment of T. cruzi and in the pathogenesis of Chagas' disease. Humoral and CMI responses were investigated in 70 T. cruzi-infected persons from an endemic area in northeastern Brazil and in 30 uninfected controls. An epidemiologic survey, physical examination, and blood evaluation were conducted for each subject. The 70 chronically infected persons were subclassified into three clinical groups: indeterminate, cardiac, and gastrointestinal. Serum was tested for antibodies to T. cruzi by hemagglutination assay, indirect immunofluorescent assay, and enzyme-linked immunosorbent assay, and for autoantibodies to tubulin. Serum levels of soluble interleukin-2 receptor (sIL-2R), albumin, and C-reactive protein (CRP) were also measured to assess one parameter each of immunosuppression, nutritional status, and inflammation. The proliferative response of peripheral blood mononuclear cells (PBMC) to T. cruzi antigens, mitogen (phytohemagglutinin), and antigen-free controls was also assessed. Our data did not reveal any significant differences in serum levels of antibodies to T. cruzi, antibodies to tubulin, albumin, CRP, or sIL-2R among the subgroups of infected individuals. The data demonstrate differences in CMI responses. Trypanosoma cruzi trypomastigote lysate stimulated proliferation of PBMC from infected persons, but not uninfected controls. Patients with symptomatic Chagas' disease (cardiac and gastrointestinal groups) had decreased cellular responses to T. cruzi lysate (median proliferation index [PI] = 3), compared with those in the indeterminate group (median PI = 9; P < 0.005). Further investigations of the mechanism of this reduced CMI response in those with chronic disease may yield insights into the pathogenesis of Chagas' disease.

Adolescent↗

Blood transfusions as pretreatment for kidney transplantation: immunization rate and effect on cellular immune response in vitro.

A group of 28 untransfused uremic patients was given five or more units of stored blood as pretreatment for kidney transplantation; 9 patients formed lymphocytotoxic antibodies against B cells and 1 patient developed multispecific antibodies against both B and T cell panels (greater than 80% reactivity). During the same period 22 previously transfused patients received up to five transfusions as pretreatment for kidney transplantation. B cell antibodies were formed by 10 patients, and 4 of these patients also formed T cell antibodies, 2 with broad reactivity. Cellular immune reactivity in vitro was studied on frozen cells from 17 randomly chosen patients. After five blood transfusions no significant changes were seen in blood lymphocyte responses to phytohemagglutinin (PHA), Concanavalin A (Con A), or in mixed lymphocyte cultures (MLC) and cell-mediated lympholysis (CML). After transfusion 3 patients got Non-A, non-B hepatitis and were withdrawn for up to six months from the transplantation list because of increased S-ALAT and S-ASAT. Of the 50 patients, 27 have received kidney grafts, 6 out of 20 who were sensitized, and 21 out of 30 who were nonsensitized. Because of positive crossmatches no patient with multispecific T cell antibodies has received a graft. We conclude that our transfusion regimen for kidney recipients has rendered barely one-third of the patients sensitized (mostly against B cells) and 3 out of 50 hypersensitized. No effect on T cell reactivity could be seen following five planned transfusions. Because fewer patients with antibodies received grafts (30% with antibodies, as compared with 70% without [P less than 0.01]) the blood transfusions seem to have led to a selection effect.

Antibodies↗

Effect of open and laparoscopic surgery on cellular immunity in a swine model.

Immune suppression associated with trauma has been demonstrated to be proportional to the magnitude of injury. Laparoscopic surgery has been shown to produce a diminished stress response compared to open surgery. Postoperative immune function, specifically cellular immunity, may be better preserved after laparoscopic surgery compared to open surgery. The aim of this study was to examine the effect of open versus laparoscopic surgery on cellular immunity in a swine model. Twenty domestic female pigs were randomly selected for laparoscopic cholecystectomy (LC) or open cholecystectomy (OC). Cellular immune functions were evaluated with delayed-type hypersensitivity (DTH) skin test and serial phytohemoagglutinin (PHA)-induced T-cell proliferation of the peripheral blood. There was a significant reduction in PHA-induced T-cell proliferation in both LC and OC groups on days 1 and 3 compared to preoperative values (p < 0.05). The reduction of mitogen-induced T-cell proliferation after LC was significantly less than after OC on day 1 (p = 0.03). The mean DTH reaction was 29.7 +/- 3.7 mm2 in the LC group compared to 13.9 +/- 1.2 mm2 in the OC group (p < 0.001). There was no difference in postoperative white blood count values between the two groups. Suppression of cellular immunity occurred after both LC and OC. The magnitude and duration of impaired cellular immunity after laparoscopic surgery was less than after open surgery as measured by T-cell proliferation and DTH response.

Animals↗