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The effect of Etofibrate (Lipo-Merz) on "in vitro" cellular immune response and on lipid parameters of men with myocardial infarction and with arteriosclerosis obliterans.

Earlier specific cell-mediated immune reactions and their modulation by different drugs were reported against human vascular antigens in patients with vascular diseases. Presently the effect of Etofibrate (Lipo-Merz) was studied on cellular immune reactions induced by human aorta with lipid plaques and on serum lipid parameters in 46 men with acute myocardial infarction and in 48 men with arteriosclerosis obliterans compared to 40 healthy controls. Leucocyte migration test and lymphocyte-mediated cytotoxicity were repeatedly investigated in the presence of human aortic extract with or without Etofibrate (2 micrograms/50 microliters). The degree of leucocyte migration inhibition and of lymphocyte-mediated cytotoxicity proved to be similar in hypherlipaemic and in normolipaemic groups. Etofibrate could decrease cellular immune reactions both in hyperlipaemic and normolipaemic patients, but its effect was more expressive in the hyperlipaemic than normolipaemic group. Three months later a reduction of cellular immune reactions was found mainly in normolipaemic patients. Ten patients with myocardial infarction and 10 arteriosclerosis obliterans patients were treated with Etofibrate (900 mg/day) for 12 weeks. After therapy, cholesterol, triglycerides, LDL concentrations were reduced, HDL level was increased and the rate of LDL:HDL decreased. Leucocyte migration inhibition and lymphocyte-mediated cytotoxicity were also diminished. This time the cellular immune reactions of treated patients were only slightly reduced "in vitro" by Etofibrate in contrast with non treated hyper- and normolipaemic patients in whom cellular immune reactions were decreased by Etofibrate similarly to the first determinations. On the basis of our observations Etofibrate may be useful in the therapy of arteriosclerotic vascular diseases with or without hyperlipaemia, because it could decrease the cellular sensitization against aortic tissue.

Adult↗

Changes of some parameters of humoral and cellular immunity in allergy to pollen.

The study of some parameters of humoral and cellular immunity in 45 pollinosis patients and 18 healthy controls, showed a deficit of humoral immunity reflected in a decrease of the IgA and IgG mean values and an increase of the IgM mean values (coefficient of correlation (r): r IgA/IgG = 0.912; r IgM/IgG = -0.316). As regards the cellular immunity the study revealed both a numeric and a functional decrease of the T lymphocytes r Th/Ts = -0.877, showing a deficit of cellular-mediated immunity.

Adult↗

Cellular immune responses to diluted and undiluted aventis pasteur smallpox vaccine.

BACKGROUND: Recent primary vaccine trials of diluted Aventis Pasteur smallpox vaccine (APSV) demonstrated that immunization "take" rates, defined by the presence of a vesicle or pustule ("take") at the inoculation site 6-11 days after immunization, did not differ between the dilution groups. To our knowledge, there have been no studies that examine the cellular immune response or that distinguish CD4(+) T cell responses from CD8(+) T cell responses after primary immunization with varying dilutions of APSV. METHODS: In the present study, we examined the cellular immune response in vaccinia-naive healthy adults (n=91) receiving inoculations with an undiluted or diluted (1:5 and 1:10) suspension of the APSV, using an intracellular cytokine staining assay. RESULTS: The diluted vaccine induced vaccinia virus (VV)-specific CD4(+) and CD8(+) T cell responses 1 month after primary immunization that were comparable to those induced by undiluted vaccine. The cellular immune responses were correlated with the reactogenicity profile of subjects and did not differ between dilution groups. Furthermore, expression of the interleukin-7 receptor alpha chain, which has been proposed to distinguish antigen-specific T cells that differentiate into long-lived memory T cells, did not differ among groups, suggesting that dilution of the vaccine does not affect the quantity of VV-specific memory T cells. CONCLUSIONS: APSV is an effective smallpox vaccine inducing strong humoral and cellular immune responses after a primary immunization even at diluted doses.

CD4-Positive T-Lymphocytes↗

Serum glycoproteins in cancer patients: first report of correlations with in vitro and in vivo parameters of cellular immunity.

Serum levels of proteins previously shown to be elevated [acute-phase proteins (APP)-haptoglobin, alpha 1-acid glycoprotein, alpha 1-antitrypsin] or depressed (alpha 2 HS-glycoprotein, prealbumin, albumin) in cancer patients were correlated with tumor extent, in vitro lymphocyte reactivity (LR) to phytohemagglutinin (PHA), and quantitative delayed hypersensivity (DH) to dinitrochlorobenzene (DNCB) in 147 preoperative patients with operable solid malignancies either confined to the primary site or with regional spread only. Compared to 58 normal controls, levels of the APP were significantly elevated, alpha 2 HS-glycoprotein and prealbumin depressed, and albumin levels unchanged in patients with either local or regional tumors. In patients with normal DH to DNCB, the APP were higher and prealbumin was lower than in controls; in patients with impaired DH to DNCB, haptoglobin and alpha 1-acid glycoprotein were higher and alpha 2 HS-glycoprotein and prealbumin lower than in patients with normal DH to DNCB. Albumin levels did not differ from normals in any of the groups. Serum protein levels appeared to be more related to the immune status of the patient than to tumor extent. The levels of the three APP correlated directly with each other but inversely with alpha 2 HS-glycoprotein and prealbumin; levels of alpha 2 HS-glycoprotein and prealbumin correlated directly with each other. Levels of haptoglobin and alpha 1-acid glycoprotein correlated inversely with LR to PHA; however, levels of alpha 2 HS-glycoprotein correlated directly with LR to PHA, and uniquely the levels of alpha 2 HS-glycoprotein and LR to PHA both showed similar changes for each of the four quantitative levels of DH to DNCB measured in the cancer patients. The data show that the proteins studied, except for albumin, correlate inversely (APP) or directly (alpha 2 HS-glycoprotein and prealbumin) with in vitro and in vivo parameters of cellular immunity. The results provide a rationale for attempts to improve depressed cellular immunity by lowering circulating levels of APP, as is being attempted in ongoing trials using plasmapheresis, and assessing the effect of exogenous alpha 2 HS-glycoprotein or prealbumin in patients with low levels of these glycoproteins and depressed cellular immunity. The correlations between serum glycoprotein levels and in vitro and in vivo parameters of cellular immunity lend rationale to investigations of the interactions of serum glycoproteins and blood cells having immunologic function that determine the level of cellular immunity expressed in vivo.

Adult↗

Sterile wounding is a minimal and sufficient trigger for a cellular immune response in Drosophila melanogaster.

An attack and oviposition by parasitic wasp Leptopilina boulardi induces a vigorous cellular immune response in Drosophila melanogaster larvae. This response is manifested by the appearance of a specialized subset of blood cells, the lamellocytes, which are the key players in the encapsulation and killing of the parasite. The formation of lamellocytes involves the activation of the Toll, the Jun kinase and the JAK/STAT pathways however the minimal requirement for initiation of lamellocyte development in the course of the cellular immune response has not been defined yet. In this study, we tested whether or not the mechanical injury itself, caused by oviposition, could provide a sufficient signal for lamellocyte development. We found that sterile wounding, comparable to that occurring during oviposition, induces normal lamellocyte development. We propose therefore that mechanical damage of the cuticle and subsequent disruption of the basal lamina is a minimal and sufficient single signal for normal lamellocyte development in the course of the cellular immune response of Drosophila.

Animals↗

Concomitant immunization by the fully antigenic counterparts prevents modulated tumor cells from escaping cellular immune elimination.

In a mathematical model of the cellular antitumor immune response, we studied the possible role of antigenic modulation as a tumor escape mechanism. Modulated tumor cells arise from normal (fully antigenic) tumor cells when the latter interact with antibodies. Modulated tumor cells demodulate when antibody concentrations are sufficiently low. Through modulation, tumor cells become less sensitive to cytotoxic macrophages (cell lysis) and contribute less to the stimulation of the immune system. These experimental data are incorporated in a model which we have analyzed previously. The model incorporates interactions between macrophages and T lymphocytes, which lead to cellular antitumor immune reactions (i.e., to cytotoxic macrophages). Parameters were derived from the immune resistance of DBA/2 mice to the SL2 tumor. Although all parameters were chosen deliberately to favor the modulation process (i.e., modulation proceeds fast, demodulation slowly, and the killing rate is reduced 50-fold), modulation is found to be a poor tumor escape mechanism. Heterogeneous populations of modulated and normal tumor cells are easily rejected. Homogeneous populations of modulated cells do escape, however. We conclude that the impact of modulation as an escape mechanism remains small because modulated tumor cells do not appear until the immune system has been stimulated (immunized) by the fully antigenic tumor cells. Thus, the elimination of modulated tumor cells generally occurs merely as a side effect of the immune response which is directed primarily against the fully antigenic tumor cells. Parameter sensitivity analysis shows that this conclusion holds true only for cellular immunity. Conversely, the parameter analysis suggests that antigenic modulation plays a deleterious role in cytotoxic antibody responses (e.g., monoclonal antibody therapy).

Animals↗

[Specific features of cellular immunity of pulmonary tuberculosis in patients with diabetes mellitus].

The parameters of cellular immunity were studied in 64 patients with pulmonary tuberculous developed in the presence of type 1 diabetes mellitus and compared with those in 36 patients with pulmonary tuberculosis alone. Patients with concomitant abnormalities showed higher depression of cellular immunity appeared as fewer T lymphocytes and their decreased capacity for blast-cell transformation than those with tuberculosis alone. Immunological parameters became normal only due to complex chemo- and immunotherapies (with T-activin). In addition, treatment outcomes improve and more rapid and frequent abacillation occurs. The development of tuberculosis in patients with diabetes mellitus is an additional indication for immunostimulant therapy with T-activin.

Adjuvants, Immunologic↗

Dendritic cells and HIV infection; immunity with viral transmission versus compromised cellular immunity?

In this commentary we propose that changes in immune activity in HIV 1 infection are secondary to two aspects of the function of dendritic antigen presenting cells (DC). Firstly DC initiate primary proliferative and cytotoxic T cell responses to HIV but disseminate virus to T cells. Secondly, balanced against the development of protective immunity is progressive inhibition of the capacity of DC to initiate primary T cell responses. With regard to viral transmission via DC, recent studies provide direct evidence that virus has evolved in vivo by passage between DC and T cells and that DC can act as a reservoir for virus. Thus, phylogenetic trees of the sequences of V3 loops of HIV viruses in individual blood samples show evolution via DC and T cells, and plasma virus can be related preferentially to that derived from DC. In functional studies, DC from asymptomatic individuals (lacking lymphadenopathy and without treatment) cause low levels of stimulation of allogeneic lymphocytes in the mixed leukocyte reaction (MLR). By contrast, lymphocytes from these patients respond to normal allogeneic DC. Our recent evidence shows that DC stimulate an MLR by transfer of alloantigens to DC of the responder type with subsequent syngeneic stimulation of T cells. The failure of T cell stimulation by DC in HIV infection therefore shows an incapacity of these DC to transfer antigenic signals to other DC but DC that acquire and present antigen directly to stimulate T cells are still functional. The latter situation provides encouragement that immunotherapy via DC may be feasible. However, DC from HIV infected individuals promote antibody production in B cells suggesting that the initial interaction of HIV with DC produces autocrine effects on DC populations that promote interaction with B cells rather than with T cells. Treatment that pushes the DC back towards stimulating T cells, despite increased viral dissemination, may promote protective immunity.

Animals↗

Local cellular immunity in the draining lymph nodes of mice after immunization with histocompatibility alloantigens.

Mice immunized with allogeneic cells exhibit a local component of cellular immunity that is confined to lymph nodes draining the site of immunization. After immunization of C3H mice by skin grafting or by i.p. or footpad injection of F1 hybrid spleen cells, draining lymph nodes show increased responsiveness toward the immunizing histocompatibility determinants for at least 3 months after immunization. This local component of immunity is not detected in a traditional graft-versus-host (GVH) assay of splenomegaly. To demonstrate this immunity, we used a GVH assay in which pieces of whole lymph nodes were grafted onto F1 hybrid host kidneys. The enlargement of each grafted node piece is taken as the measure of its immunological responsiveness. We interpret our results to indicate that this node-onto-kidney assay detects the contribution of a relatively immobile donor cell population that exerts its effects in lymph nodes local to, but not distant from, the site of immunization.

Animals↗

Cellular immunity to P. acnes in the normal population and patients with acne vulgaris.

Patients with varying degrees of acne, acne-free adult controls and samples of cord blood were investigated for cell mediated immunity to P. acnes using a leukocyte migration inhibition test. Despite the fact that the mean migration index tended to decrease with acne severity, only the patients with severe acne showed cell-mediated immunity. It is suggested that when cellular immunity arises it is a late event which may contribute to inflammation but is probably not a factor in its initiation.

Acne Vulgaris↗

[Humoral and cellular immunity in mice immunized with mutagenic NTG-attenuated cercariae of Schistosoma japonicum].

Observation was made on humoral and cellular immunity in mice immunized with NTG-attenuated cercariae. Results showed that the specific antibody in serum of immunized mice increased gradually. The titer by ELISA and IFA were more than 1:1,280 respectively at week 7 post-immunization with NTG-attenuated cercariae (15 min. pc or 60 min. ip). SDS-PAGE electrophoresis showed that there was an extra-band of IgG with MW, between 50,000 and 40,000 in the serum of immunized mice and there was no obvious difference in IgM bands. It suggested that there were differences in not only the increase of antibody titre, but also the composition of antibody post-immunization. The results also indicated that there were differences in levels of lymphocyte proliferative response to schistosome antigens at different weeks post-immunization. The proliferative response to SEA was greater in immunized mice than in infected mice, especially in lymph node lymphocytes. It suggested that NTG-attenuated cercariae did stimulate mice to produce immunity. The dynamic characteristics of humoral and cellular immunity may play roles in the induction of protective immunity against S. japonicum.

Animals↗

Immunization with cytoplasmic repetitive antigen and flagellar repetitive antigen of Trypanosoma cruzi stimulates a cellular immune response in mice.

In previous studies, we demonstrated that CRA and FRA recombinant proteins, used for diagnosis of Chagas' disease, elicited a humoral immune response in susceptible and resistant mice. To understand better the immune response to these proteins, we have evaluated, the cellular immune response in CRA- and in FRA-immunized BALB/c and C57BL/6 mice. A specific cellular lymphoproliferative response was observed in both strains of mice. Spleen cell cultures mainly from CRA-immunized C57BL/6 and FRA-immunized BALB/c mice produced high levels of IFN-y, indicating the induction of a Type 1 immune response. Regarding the T cell subsets, CD4+ T cells were the major source of IFN-y in CRA- and FRA-immunized mice. These results suggest that CRA and FRA are important immunogens in inducing a Type 1 immune response and that they may be considered as potential vaccine antigens.

Animals↗

[Effect of zinc on the cellular immunity and NK cell activity in acute heat exposed rats].

To study the effects of zinc on the cellular immunity and NK cell activity in acute heat-exposed rats. Rats were fed with dietary containing high, moderate and low zinc for 15 days. The concentrations of zinc in high, moderate and low zinc dietary are 92.20 mg/kg, 45.61 mg/kg and 21.70 mg/kg respectively. After exposed to acute heat (41.5 degrees C) for 5 min, 30 min and 60 min, the rats were killed and the cellular immunity and NK cell activity were measured. The proliferation of lymphocyte and the NK cell activity were higher in high zinc group than in moderate and low zinc groups no matter the rats were exposed to heat or not. Zinc can improve the cellular immunity and NK cell activity in acute heat exposed rats.

Animals↗

Local adoptive transfer of antitumor cellular immunity to xenogeneic animals studied with a rapid radioisotopic footpad assay.

The antitumor cellular immune response to Gross virus-induced rat tumor cells in F344 rats, as measured by a sensitive radioisotopic footpad assay, was adoptively transferred to syngeneic rats and to xenogeneic irradiated BALB/c mice. Xenogeneic transfer was accomplished by the injection of a mixture of rat tumor cells and syngeneic spleen cells, peritoneal exudate cells, or blood lymphocytes from specific immune rats into the footpads of mice. Peritoneal exudate cells produced the strongest footpad reaction in xenogeneic recipients. Use of the xenogeneic adoptive transfer system in a bioassay for human antitumor immunity appeared feasible.

Animals↗

Humoral and cellular immune responses to an envelope-associated antigen of herpes simplex virus.

The humoral and cellular immune responses of rabbits and guinea pigs to the envelope-associated antigen of herpes simplex virus type I were studied. Neutralizing antibody (at high titer) and lymphocytes reactive to herpes simplex virus were detected in both guinea pigs and rabbits after immunization with the antigen. In a standard assay of cellular immunity to herpes simplex virus, the antigen stimulated blast transformation of herpes simplex virus-reactive splenic lymphocytes in vitro. Furthermore, immunization of rabbits with the envelope-associated antigen protected the animals from a lethal dose of live herpes simplex virus. Thus an antigen of herpes simplex virus can be prepared which contains neither infectious nor noninfectious viral particles and which stimulates immunity to the virus in laboratory animals.

Animals↗

[Induction of EIAV-specific cellular immune response by attenuated EIAV vaccine].

AIM: To elucidate cellular immune protective mechanism of EIAV. METHODS: Four horses were immunized with (DLV) by subcutaneous injection and 2 horses with 0.85% sodium chloride as the negative control. Rectal temperatures and clinical features were recorded daily. Whole blood samples were collected, from which PBMC were separated and used for CTL assay and lymphocyte proliferation assay. RESULTS: The target cells were activated by PWM and treated with DLV or recombinant vaccinia vectors expressing DLV and LN Gag or Env separately. The percentage of EIAV-specific CTL lysis was under 5% in the negative control group, however, that was 20% to 30% in the group of immunized horses. The stimulation index (SI) from proliferation assay was 3 in the group immunized with attenuated DLV vaccine. CONCLUSION: The results indicated that EIAV-specific cellular immune-response induced by DLV immunization may contribute to the immune protective effect against EIAV virus infection.

Animals↗

Humoral and cellular immune responses to Salmonella typhi in patients with typhoid fever.

Humoral and cellular immune responses to Salmonella typhi have been studied in nine children with typhoid fever. By using dot immunobinding assay, anti-O-polysaccharide chain and antilipid A antibody titers have been evaluated during the course of the disease. Anti-O-polysaccharide chain antibody titers are lower at the first week and increase up to the third week of the infection. On the other hand, antilipid A antibody levels, which are already higher at the beginning of the disease, progressively augment during the following weeks. Concerning cellular immunity to S. typhi, antibacterial activity mediated by typhoid peripheral mononuclear cells has been determined. Results show this function to be depressed in the initial phase of typhoid, increasing with the time. Together, these data bring new insight on immunity in typhoid patients.

Antibodies, Bacterial↗