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Experimental salmonellosis. VII. In vitro transfer of cellular immunity by ribosomal fraction of mouse mononuclear phagocytes.

Sato, Ichiei (Gunma University, Maebashi, Japan), and Susumu Mitsuhashi. Experimental salmonellosis. VII. In vitro transfer of cellular immunity by ribosomal fraction of mouse mononuclear phagocytes. J. Bacteriol. 90:1194-1199. 1965.-The mononuclear phagocytes (termed monocytes) of mice hyperimmunized with live vaccine of Salmonella enteritidis inhibited the intracellular growth of virulent strain 116-54 of S. enteritidis. Also, the monocytes withstood the degeneration of cells caused by the phagocytosis of bacteria in the absence of immune serum in the tissue culture medium, termed cellular immunity. When the nonimmune monocytes were incubated with the ribosomal fraction of immune monocytes, obtained from the abdominal cavity of mice hyperimmunized with live vaccine of S. enteritidis, they acquired cellular immunity, but the monocytes did not acquire immunity when ribosomal fractions from normal mouse monocytes or from the monocytes of mice immunized with killed vaccine of S. enteritidis were used. The transfer agent present in the ribosomal fraction of immune monocytes was inactivated by treatment with ribonuclease but not with deoxyribonuclease or with trypsin.

Animals↗

Stability of individual differences in cellular immune responses to acute psychological stress.

To determine the stability of individual differences in cellular immune reactions to acute mental stress, we correlated enumerative and functional lymphocyte responses to an evaluative speech task across two experimental sessions scheduled 2 weeks apart in 30 young men. Relative to pretask baseline measurements, the speech stressor elicited a diminished proliferative response to phytohemagglutinin and concanavalin A, a decrease in circulating CD19 lymphocytes, and an increase in both CD8 and CD56 lymphocytes across the two occasions of testing. Test-retest correlations were significant for the magnitude of change in proliferative response to PHA (r = .50, p < .005) and in numbers of circulating CD8 and CD56 cells (r = .53, and .42, respectively; p's < .02). Concomitant cardiovascular responses also correlated significantly over the two experimental sessions (heart rate: r = .78, p < .0001; systolic and diastolic blood pressure: r = .79 and .48, p < .0001 and .007). These data provide initial evidence that interindividual variability of cellular immune responses to acute psychological stress is moderately reproducible on retesting and may therefore denote a stable dimension of individual differences.

Adolescent↗

Status of local cellular immunity in interferon-responsive and -nonresponsive human papillomavirus-associated lesions.

BACKGROUND AND OBJECTIVES: Anogenital warts are caused by human papillomaviruses (HPVs), which should induce cellular immune responses in immunocompetent patients. However, the natural history of these warts shows considerable variation between persons, ranging from spontaneous regression to prolonged persistence. In addition, the efficiency of immunologically based modalities for the therapy of anogenital warts, such as interferon (IFN) treatment, is highly variable. METHODS: Considering that preexisting conditions of the host are important factors in an appropriate immune response, the authors determined the pretreatment status of local cell-mediated immune response to HPV infection by reverse transcription-polymerase chain reaction in patients with condyloma acuminatum, who later received IFN treatment and responded well or poorly to that therapy. RESULTS AND CONCLUSIONS: The authors found that biopsies from nonresponders were depleted markedly in Langerhans cells, leading to decreases in major histocompatibility complex class II expression and, therefore, to diminished attraction of CD4+ T cells. An inappropriate major histocompatibility complex class I expression also was observed in those nonresponders with decreased CD8+ levels. The mRNA levels of cytokines (interleukin-1a, interleukin-1b, granulocyte-macrophage-colony stimulating factor, tumor necrosis factor that participate in immune responses were low in nonresponders. In contrast, responders demonstrated high macrophage-natural killer cell (CD16-positive) and activated CD4 (IL-2, interferon gamma-positive, TH1 cells) T-cell recruitment against HPV-infected keratinocytes, which is consistent with a delayed-type hypersensitivity-like cellular immune response. Lack of immune response in nonresponders appeared to correlate with high expression levels of the HPV E7 gene. These differences in local cellular immunity might determine the response rate of HPV-infected cells to immunomodulatory therapies.

Antigen-Presenting Cells↗

[Study on cellular immunity in children with respiratory syncytial virus associated acute lower respiratory infection].

For exploring cellular immunity disturbances in children with acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV) the level of interleukin-2 (IL-2) soluble interleukin-2 receptor (sIL- 2R), the expression rate of interleukin-2 receptor (IL-2R) on T cells and percentage of T lymphocyte subsets were determined in peripheral blood of 25 acute cases. The results showed that compared acute stage of RSV associated ALRI with recovery stage and control group, the level of peripheral blood IL-2 and expression rates of IL-2R decreased but the level of sIL-2R increased. The level of IL-2 had positive correlation with IL-2R and percentage of CD4+ cells, but had negative correlation with sIL-2R and percentage of CD8+ cells. The plasma sIL-2R level had negative correlation with expression rate of IL-2R, but had a positive correlation with clinical severity. These results suggested that human body had a functional disturbance in cellular immunity when infected with RSV.

Acute Disease↗

[Study on the cellular immune function and cytokines in aplastic anemia patients].

OBJECTIVE: To evaluate the effects of cellular immune function and cytokines on the pathogenesis of aplastic anemia (AA) and its clinical significance. METHODS: T lymphocyte subsets and HLA-DR antigen expression in the peripheral blood cells were assayed, and the levels of G-CSF, IL-6, TNF alpha, IFN alpha and IL-8 in the PBMNC culture supernatants were determined in 38 AA patients and 20 normal control with APAAP and ELISA methods. RESULTS: CD4+ cells, CD4+/CD8+ cells and G-CSF level were lower, and CD8+ cells, HLA-DR+ cells and IL-6, TNF alpha, IFN alpha and IL-8 levels were higher in AA patients than in normal controls. The level of G-CSF was positively correlated with CD4+ cells and CD4+/CD8+ cells and negatively with IFN alpha level. IL-6 level was negatively correlated with WBC count and CD4+ cells. TNF alpha level was positively correlated with CD8+ cells and negatively with CD4+/CD8+ cells. IL-8 level was positively correlated with CD8+ cells and HLA-DR+ cells. CONCLUSION: The cellular immune dysfunction and cytokine aberration participate in the pathogenesis of AA.

Adult↗

[Determinations of antiovarian antibodies and cellular immunity functions in patients with premature ovarian failure].

OBJECTIVE: To investigate the variations of cellular immunity function and its relationship with antiovarian antibodies (AOAb) in patients with premature ovarian failure (POF). METHODS: Serum AOAb, T-lymphocyte subsets and leukocyteprocoagulant activity (LPCA) to ovarian antigens of peripheral blood were examined in 30 normal women (control group) and 30 patients with POF (POF group). RESULTS: The mean serum AOAb level in POF group was significantly higher than that in control group (6.80 +/- 1.9 kU/L vs 1.39 +/- 0.72 kU/L, P < 0.01). The percentage of CD3+, CD4+ cells increased significantly (65.42 +/- 5.31% and 44.79 +/- 5.90%, respectively), the percentage of CD8- cells was significantly lower (25.63 +/- 4.26%) and the ratio of CD4+/CD8+ increased (1.66 +/- 0.27) in POF group when compared with control group (P < 0.01). The positive rate of AOAb in patients who had elevated ratio of CD4+/CD8+ was significantly higher than those with normal CD4+/CD8+ ratio (85.7%, 18/21 vs 3/9; P < 0.01). The level of LPCA was elevated in POF patients with positive AOAb, and was correlated positively with the level of AOAb (chi 2 = 8.378, P < 0.01). CONCLUSIONS: These data showed that cellular immunity and humoral immunity to ovarian antigens can be concurrently produced in POF patients, and suggested that pathogenesis of POF may be associated with immune factors.

Adult↗

Study of modulatory effects of Olimunostim on cellular immunity in healthy humans.

To objectivize potential modulatory effects of polybacterial lysate Olimunostim on cellular immunity, the T-lymphocyte subpopulations and lymphocyte reactivity to mitogens were followed up in 10 healthy volunteers subjected to Olimunostim application and parallelly in 6 healthy individuals receiving placebo. The preparation, which was applied perorally in seven consecutive daily doses, had no effects on T-lymphocytes and their subpopulations and exerted only a limited influence on lymphocyte reactivity to mitogens. Both the moderate suppression of proliferative response to Con A and PWM, observed after the application of the three doses of Olimunostim, and the insignificantly enhanced response to PHA and Con A, revealed shortly after the last dose was given, were only of transient character and in comparison with the control group were not proved to be statistically significant. To explain the discordance of these results with the recently reported modulatory effects of Olimunostim on murine lymphocytes it is suggested, that the performed tests using the peripheral blood lymphocytes cannot mirror the processes developing in the diseased tissues. With respect to this presumption and also to the observations of enhanced immunomodulatory effect of Olimunostim on terrain altered by infection, it is proposed to investigate cellular immune parameters in specific disease sites of Olimunostim treated patients suffering from recurrent infections.

Adjuvants, Immunologic↗

Effect of zinc and melatonin supplementation on cellular immunity in rats with toxoplasmosis.

The effects of zinc (Zn) and/or melatonin supplementation on cellular immunity were investigated in rats infested with Toxoplasma gondii. Fifty Sprague-Dawley male rats were used for this study. All animals were fed a normal diet, ad libitum, containing 97 mg Zn/kg. They were divided into five experimental groups, as follows. Group I (n = 10) received intraperitoneal injections of zinc sulfate at a dose of 3 mg/kg/d for 3 wk. Group II (n = 10) received intraperitoneal injections of melatonin at a dose of 3 mg/kg/d for 3 wk. Group III (n = 10) received intraperitoneal injections of zinc sulfate (3 mg/kg/d) and melatonin (3 mg/kg/d) for 3 wk. Group IV (n = 10) was infested controls. Group V (n = 10) was healthy controls. There were no differences in the percentage of CD3+ lymphocytes among all groups. For groups I-III, the CD4+ and CD8+ ratios were higher than those of the groups IV and V controls (p<0.01). Similarly, the total lymphocyte ratios in groups I-III were higher than those of infested and healthy controls (p<0.01). The total lymphocyte ratios in group III were significantly higher than those of groups I and II (p<0.01). The plasma Zn levels in the supplemented groups were significantly higher than those of control groups IV and V (p<0.01). These results suggest that melatonin and/or Zn supplementation may activate cellular immunity by stimulating CD4+ and CD8+ production in infected rats with T. gondii.

Animals↗

HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals.

HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their HIV-seropositive partners; antibodies were not detected in low-risk controls. Envelope protein (Env) peptide-stimulated interleukin-2 (IL-2) production by peripheral blood mononuclear cells (PBMCs) was detected in 9 out of 16 ESNs, 5 out of 16 HIV-infected patients and 1 out of 50 controls. Env peptide-stimulated PBMCs of ESNs produced more IL-2 and less IL-10 compared with those of HIV-infected individuals; no differences were observed in chemokine production or in CCR5 expression. These data demonstrate that a compartmentalized immune response to pathogens is possible in humans and raise the possibility of protective roles for cell-mediated immunity and mucosal IgA in HIV-seronegative individuals exposed to HIV.

Adult↗

Cellular immunity (T-cell subset using monoclonal antibody) in tuberculosis, melioidosis, pasteurellosis, penicilliosis; and role of levamisole and isoprinosine.

In vitro and in vivo evaluation of cellular immunity (T-cell subset--using monoclonal antibody--immunofluorescent staining technique; E-rosette formation to 2.4-Dinitrochlorobenzene reaction) were made in tuberculosis, melioidosis, pasteurellosis and penicilliosis. The data demonstrate depressed cellular immunity especially a significant decrease in numbers of T-helper cells and T-helper/T-suppressor subset ratio fell to less than 1.0. Of greater importance, in tuberculous patients and patients with melioidosis treated with levamisole, 150 mg/day, twice a week, along with a specific antitubercular or antimicrobial agent for appropriate duration, improved faster both clinically, microbiologically and in cellular immunity.

Adult↗

In vitro whole-blood analysis of cellular immunity in patients with active coccidioidomycosis by using the antigen preparation T27K.

Measurement of cellular immunity in human coccidioidomycosis has important diagnostic and prognostic implications. The coccidioidin skin test has been the standard for the measurement of this, but it is not available in the United States. We examined the utility of measuring surface expression of CD69 on T lymphocytes in whole blood incubated with the coccidioidal antigen preparation T27K as an alternative to the skin test. Seventy donors with active coccidioidomycosis were studied. The mean fluorescent intensity (MFI) of CD69 expression on CD3 lymphocytes in response to T27K was 28.61 +/- 1.77, significantly greater than the control response of 11.45 +/- 0.78 (P < 0.001). The MFI CD69 response to T27K above that for the control (MFI CD69 above control) was 6.35 +/- 2.18 for seven subjects with disseminated coccidioidomycosis who were studied within 5 months of diagnosis. This was significantly below the value of 20.17 +/- 3.17 for 18 subjects with pulmonary coccidioidomycosis studied within 5 months of diagnosis and the value of 19.58 +/- 2.91 for 27 subjects with disseminated coccidioidomycosis studied after 5 months of diagnosis (for both, P < 0.05). There was an inverse correlation between coccidioidal clinical score and MFI CD69 above control for all 34 subjects with disseminated coccidioidomycosis (r = 0.362; P = 0.036) but not for the 36 subjects with pulmonary disease (r < 0.001; P = 0.993). Among 30 subjects for whom data were available, there was a highly significant association between the MFI CD69 above control and the supernatant concentrations of gamma interferon, interleukin-2 (IL-2), and tumor necrosis factor alpha (for all, P < 0.001), but not for IL-4, IL-5, or IL-10. These data indicate that in vitro assessment of CD69 expression on T lymphocytes by using T27K may be a useful measure of cellular immune response among subjects with active coccidioidomycosis.

Adult↗

Reconstitution of the cellular immune response after autologous peripheral blood stem cell transplantation in patients with non-Hodgkin's lymphoma.

Peripheral blood stem cell (PBSC) transplants may be depleted of lymphoid progenitors, thereby disabling the cellular immune response against viral pathogens after autologous PBSC transplantation (PBSCT). To monitor the cellular immune reconstitution after autologous PBSCT, we investigated the cytolytic activity (CLA) of peripheral blood T lymphocytes against Epstein-Barr virus (EBV) in 13 patients with non-Hodgkin's lymphoma or multiple myeloma. The individual EBV-directed CLA (EBV-CLA) was determined by calculating the number of cytolytic effector cells in 106 T cells needed to lyse 25% of autologous EBV-transformed B-lymphoblastoid cells, expressed as lytic units (LU25). During the first 6 months after PBSCT, the EBV-CLA was only 14.6% of the response of healthy controls (median 4. 8 vs. 32.9 LU25). Thereafter, the EBV-CLA increased to 28.15 LU25 (median) or 86% of healthy controls. Monthly follow-up analyses in five selected patients showed that the EBV-CLA was barely detectable at 4 weeks and recovered at 8-12 weeks after PBSCT in four out of five patients. Effector cells consisted mostly of CD8-positive T lymphocytes, with small CD4- and CD3/CD56-positive lymphocyte fractions. These results suggest that the reconstitution of the cellular immune response against EBV takes 8-12 weeks after autologous PBSCT.

Female↗

[Suggestions on the control and stimulation of cellular immunity in cancer].

Seventy patients suffering from cancer have been treated since 1969 with intracutaneous injections of autogenous carcinoma cells. This should stimulate cellular immunity through the skin. A stimulation and reactivation of cellular immunity seems to be possible. The cellular reaction at the injection site supplied useful hints for the evaluation of the state of immunity. The possibility of improving cellular resistance through immune gamma globulin in pigs treated with carcinoma cells is discussed.

Humans↗

The prevalence of cellular immunity to coccidioidomycosis in a highly endemic area.

Intradermal skin test reactivity to spherulin and coccidioidin and in vitro spherulin-induced lymphocyte transformation were used to assess cellular immunity in healthy subjects and patients with acute, self-limited coccidioidomycosis (cocci). The objectives of this study were to evaluate the relative sensitivities of the two assays in assessing cellular immunity to cocci, especially in long-term residents of an endemic area (Tucson) and, based on data from both assays, determine the prevalence of detectable cellular immunity to cocci in this highly endemic area. The lymphocyte transformation assay appeared to be more sensitive than the skin test in assessing long-term immune status, and the prevalence of detectable immunity to cocci in this highly endemic area was only 75% in long-term residents. This is much lower than previous prevalence estimates (90%) in other endemic areas. The absence of a demonstrable cell-mediated immunity may indicate either no prior antigen exposure (infection) or previous remote exposure with a diminished immune response (no reexposure to boost immunity). A possible explanation for the lower prevalence of immunity to cocci in this endemic area may relate to the increased urbanization of the Southwest in the past several years. Therefore, the clinical suspicion of acute cocci should not be restricted to recent arrivals to endemic areas.

Arizona↗

Cellular immune reactions against common antigen, small intestine, and colon antigen in patients with Crohn's disease, ulcerative colitis, and cirrhosis of the liver.

Patients with ulcerative colitis showed in 71-93%, patients with cirrhosis of the liver in 64-91%, cellular immunity against Common Antigen (CA) and human fetal intestinal antigens as measured by the leucocyte migration test (LMIT). Patients with Crohn's disease exhibited cellular immune reactions to a lesser degree - from these only patients without immunosuppressive therapy differed significantly from normal controls (p less than 0.05). Approximately 30% of patients with Crohn's disease and ulcerative colitis had elevated antibody titers against intestinal antigens and CA. A high percentage of patients in both diseases showed a reciprocal relationship between cellular and humoral immunity. It was concluded that Crohn's disease and ulcerative colitis can be separated in most cases using intestinal antigens and CA in the LMIT. The occurrence of cellular immunity against these antigens cannot be interpreted as being the only pathogenetic principle in these two diseases. It is also concluded that there appears to be only a weak immune tolerance against intestinal antigens. The high percentage of cellular immune reactions in patients with cirrhosis of the liver demonstrates that this group may have an impairment of the physiological elimination of antigens by the liver.

Antibodies↗

[Study of cellular immunity in patients with Mediterranean visceral leishmaniasis].

Cellular immunity against Leishmania infantum antigens was studied in visceral leishmaniasis patients and healthy subjects living in a endemic area. Only the healthy subjects were TTL positive with production of gamma interferon, whereas the visceral leishmaniasis patients presented a transitory inhibition of their specific cellular response mechanisms.

Adult↗

Heat shock protein 70 / MAGE-1 tumor vaccine can enhance the potency of MAGE-1-specific cellular immune responses in vivo.

The cancer-testis antigen encoded by the MAGE-1 gene is an attractive antigen in tumor immunotherapy because it can be processed as a foreign antigen by the immune system and generate tumor-specific cellular immune response in vivo. However, increase of the potency of MAGE-1 DNA vaccines is still needed. The high degree of sequence homology and intrinsic immunogenicity of heat shock protein 70 (HSP70) have prompted the suggestion that HSP70 might have immunotherapeutic potential, as HSP70 purified from malignant and virally infected cells can transfer and deliver antigenic peptides to antigen-presenting cells to elicit peptide-specific immunity. In this research, we evaluated the enhancement of linkage of Mycobacterium tuberculosis HSP70 to MAGE-1 gene of the potency of antigen-specific immunity elicited by naked DNA vaccines. We found that vaccines containing MAGE-1-HSP70 fusion genes enhanced the frequency of MAGE-1-specific cytotoxic T cells in contract to vaccines containing the MAGE-1 gene alone. More importantly, the fusion converted a less effective DNA vaccine into one with significant potency against established MAGE-1-expressing tumors. These results indicate that linkage of HSP70 to MAGE-1 gene may greatly enhance the potency of DNA vaccines, and generate specific antitumor immunity against MAGE-1-expressing tumors.

Animals↗

Recurrent aphthous ulceration with zinc deficiency and cellular immune deficiency.

Zinc deficiency (serum zinc level 65 micrograms/dl) and cellular immune deficiency (confirmed by lymphoblastic transformation assay) were found in a 15-year-old boy who had had recurrent aphthous ulceration for 6 years. Despite the previous therapy (orally administered steroid, isoprinosine, interferon, lysozyme, and local treatment), the ulcers recurred monthly. After 3 months of zinc therapy (50 mg zinc sulfate orally three times daily) the aphthae disappeared and did not reappear for 1 year. The lymphoblastic transformation activity and serum zinc levels were also normalized with this treatment.

Child↗