Impairment Of Cellular Immune Response Research Articles

Liver function parameters of patients on antiretroviral therapy attending al-noury specialist hospital Kano, Nigeria

Context: The hallmark of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) infection is the depletion of CD4hearing cells, especially the T helper cells, resulting in impairment of cellular immune response. The introduction of antiretroviral (ARV) therapy which has changed HIV/AIDS infection into a clinically wieldy disease is a progression development. Aims: The aim of the study was to evaluate the liver function parameters of patients ARV therapy attending Al-Noury Specialist Hospital Kano, Nigeria. Settings and Design: The study is a cross-sectional prospective study. Subjects and Methods: This work evaluated the effect of fixed dose combination of stavudine, lamivudine, and nevirapine on CD4cell counts and liver function parameters of 150 adult patients with a mean age of 34 years for 1 year. The measurement of serum alkaline phosphates, billirubin, and aminotransferases was analyzed using the reflection machine. Statistical Analysis Used: Data generated were analyzed using SPSS version 20.0. Logistic regression analysis was used to identify the significant predictors. Results: Of the 150 patients enrolled for the study, only 120 (180%) of them consisting of 82 (68.3%) males and 38 (31.7%) females were consistent with respect to adherence to therapy and submission to laboratory assessment. The findings of this study showed that CD4T-Cells, bilirubin, and alkaline phosphates had statistically significant changes (P > 0.05). Conclusions: Although the treatment outcome of patients with ARV indicates good response, evidence points to severe hepatocellular damage which may become life-threatening, especially for long-term users. We therefore recommend regular livers enzyme profile assessment as part of the integrated management of HIV/AIDS patients on ARV therapy.

Impaired NK cells and increased T regulatory cell numbers during cytotoxic maintenance therapy in AML

Cyclic cytotoxic maintenance therapy can be applied to patients with AML in post-remission. We studied the immune status of AML patients in complete remission and the effect of maintenance therapy on different immune cell populations. Patients in complete remission had reduced NK, TH and Treg counts and a reduced NK activation capacity. In the course of cytotoxic maintenance therapy, NK counts further declined, while TH and Treg cells increased, with lower proliferative potential of TH cells. We conclude that immunotherapeutic approaches in post-remission have to consider reduced NK cell function and further impairment of cellular immune responses during cytotoxic therapy.

Chronic Infections with Hepatotropic Viruses: Mechanisms of Impairment of Cellular Immune Responses

Chronic hepatitis B and C cause significant morbidity and mortality worldwide. Antiviral therapy suppresses but does not eliminate chronic hepatitis B virus (HBV) infection, and it is effective in only half of all hepatitis C virus (HCV)-infected patients. Because adaptive immune responses are associated with spontaneous resolution of acute HBV and HCV infection, therapeutic enhancement of immune responses has been proposed as alternative or supplementary therapy for chronic infection. However, all efforts have been hampered by poor proliferation and effector functions of HBV- and HCV-specific CD4 and CD8 T cells, which are thought to be due to T cell exhaustion, high antigenic load, and viral escape. Recent studies revealed that endogenous factors, such as regulatory T cells, immunosuppressive cytokines, and inhibitory receptors, also contribute to the impairment of virus-specific T cell responses in chronic infection, perhaps reflecting the host's attempt to protect itself against immune-mediated pathology. These endogenous mechanisms and potential avenues to revert them are the subject of this review.

Sustained virological response to peginterferon plus ribavirin in chronic hepatitis C genotype 1 patients is associated with a persistent Th1 immune response

An impairment of cellular immune response may contribute to the persistency of hepatitis C virus infection. To analyse the Th1/Th2 cytokine profile in peripheral blood CD4(+) and CD8(+) T cells from patients with chronic hepatitis C (CHC) during treatment with pegylated interferon-alpha2a plus ribavirin and to correlate the Th1/Th2 balance with virological response (SVR). Prospective longitudinal study: 44 naïve genotype 1 CHC patients received PEG-IFNalpha2a plus ribavirin for 48 weeks: 26 (59.1%) achieved a SVR, 13 relapsed (29.5%) and 5 (11.4%) were non-responders. Sixteen healthy controls were analysed. The production of IL-4, IFNgamma and TNFalpha by CD4(+) and CD8(+) T cells was measured using flow cytometry, both in resting and phorbol-ester-stimulated cells. First three months of treatment: the synthesis of TNFalpha by phorbol-ester-stimulated-CD4(+) T cells was higher in patients with SVR (P < 0.01). At the end of treatment, SVR was associated with higher intracellular expression of IFNgamma by stimulated-CD4(+) and CD8(+) T cells (P < 0.05). At the end of follow-up, a higher intracellular expression of IFNgamma by CD4(+) T cells was associated with a SVR. A Th1-type immune response was associated with achievement of a SVR, as indicated by the persistent elevation of intracellular IFNgamma and TNFalpha.

Cytokines produced by susceptible and resistant mice in the course of Paracoccidioides brasiliensis infection.

Paracoccidioidomycosis (PCM) is the most prevalent deep mycosis in Latin America and presents a wide spectrum of clinical manifestations. We established a genetically controlled murine model of PCM, where A/Sn mice develop an infection which mimics the benign disease (immune responses which favor cellular immunity) and B10.A animals present the progressive disseminated form of PCM (preferential activation of B cells and impairment of cellular immune responses). To understand the immunoregulatory phenomena associated with resistance and susceptibility in experimental PCM, A/Sn and B10.A mice were studied regarding antigen-elicited secretion of monokines (TNF-alpha and TGF-beta) and type-1 (IL-2 and IFN-gamma) and type-2 (IL-4,5,10) cytokines. Total lymph node cells from resistant mice infected i.p. with P. brasiliensis produced early and sustained levels of IFN-gamma and IL-2; type-2 cytokines (IL-4 and IL-5) started to appear 8 weeks after infection. In contrast, susceptible mice produced low levels of IFN-gamma concomitant with significant levels of IL-5 and IL-10 early in the infection. In the chronic phase of the disease, susceptible animals presented a transitory secretion of IL-2, and IL-4. In the pulmonary infection IL-4, IL-5 and IL-10 were preferentially detected in the lung cells washings of susceptible animals. After in vitro challenge with fungal antigens, normal peritoneal macrophages from B10.A mice secreted high levels of TGF-beta and low levels of TNF-alpha. In contrast, macrophages from A/Sn animals released high levels of TNF-alpha associated with a small production of TGF-beta. The in vivo depletion of IFN-gamma not only abrogated the resistance of A/Sn mice but also diminished the relative resistance of B10.A animals. The in vivo depletion of IL-4 did not alter the disease outcome, whereas administration of rIL-12 significantly enhanced resistance in susceptible animals. Taken together, these results suggest that an early secretion of high levels of TNF-alpha and IFN-gamma followed by a sustained secretion of IL-2 and IFN-gamma plays a dominant role in the resistance mechanisms to P. brasiliensis infection. In contrast, an early and ephemeral secretion of low levels of TNF-alpha and IFN-gamma associated with production of IL-5, IL-10 and TGF-beta characterizes the progressive disease of susceptible animals.

The in vitro Effect of Pidotimod on Some Immune Functions in Cancer Patients

There are several reports concerning an impairment of cellular immune response in patients affected by malignant disease. The aim of this study was to evaluate the in vitro effect of Pidotimod, a synthetic biological response modifier, on some immune functions in 14 cancer patients. In particular, we showed that these subjects had a significantly reduced peripheral blood mononuclear cell (PBMC) proliferation both in response to PHA and to Con A in comparison with a group of healthy subjects. Besides, they showed a significantly reduced PBMC IL2 production, which was evaluated both through an ELISA method and a biological assay. The in vitro addition of increasing concentrations of Pidotimod (10, 25 and 50 ug/ml) was able to enhance PBMC proliferation and IL2 production significantly. However, in spite of the addition of Pidotimod, both immune functions in our neoplastic patients did not reach normal values.

Prenatal diazepam induced persisting downregulation of peripheral (ω3) benzodiazepine receptors on rat splenic macrophages

Prenatal treatment with a low dose of diazepam (1.25mg/kg/d, gestational day 14–20) has previously been found to cause longterm impairment of cellular immune responses in rat offspring. A possible site of action of diazepam, i.e., the peripheral-type (ω3) benzodiazepine receptor, was characterized on splenic macrophages as well as on a rat splenic cell preparation containing mainly lymphocytes. In membranes of both preparations, [3H]PK 11195 bound to a single site which in competition experiments exhibited characteristics of the (ω3) site. Prenatal exposure to diazepam was followed, at 8 weeks of life, by a marked decrease in maximal binding capacity (Bmax) of spleen macrophage membranes in offspring of both sexes, while membranes of the splenic cell preparation exhibited an increase of the dissociation constant of [3H]PK 11195 at 2 and 8 weeks of life. Both types of delayed effects may reduce the metabolic capacity of these immune cells, in which we have also observed deficits of cytokine release.

Lymphocyte subsets, phytohaemagglutinin responsiveness of blood lymphocytes, and interleukin 2 production in sarcoidosis.

To test the possibility that T lymphocyte subset imbalance and interleukin 2 (IL2) play a part in the impairment of cellular immune response in sarcoidosis, the proportion of T lymphocyte subsets in peripheral blood and alveolar lavage fluid from 21 patients with sarcoidosis was studied, monoclonal antibodies OKT3, OKT4, and OKT8 being used. Lectin induced production of IL2 and phytohaemagglutinin (PHA) responsiveness of peripheral blood lymphocytes were investigated. The percentage of both OKT3+ and OKT4+ T lymphocytes was significantly lower in peripheral blood from patients with sarcoidosis than in control subjects (control 63% and 46%), more so in patients with chronic sarcoidosis (44% and 23%) than in patients with recent sarcoidosis (56% and 38%). PHA induced IL2 production from peripheral blood lymphocytes did not differ between patients with sarcoidosis and control subjects. There was a significant positive correlation between PHA responsiveness and the percentage of blood OKT3+ and OKT4+ cells. Peripheral blood lymphocyte PHA responsiveness was decreased only in patients with an OKT4/OKT8 ratio of less than 1.5. Finally, late addition of exogenous IL2 to the culture medium on day 5 increased 3(H)Tdr incorporation by PHA stimulated blasts in peripheral blood lymphocytes from normal subjects, but not from those of patients with sarcoidosis. The data suggest that the impairment of cellular immune response in patients with sarcoidosis could in part reflect a decrease in the percentage of blood T helper lymphocytes and impaired IL2 receptors at the surface of stimulated lymphocytes.

Impaired Cell-Mediated Immune Response in Patients with Congenital Rubella: Correlation with Gestational Age at Time of Infection

Lymphocyte transformation, interferon, and leukocyte migration inhibition factor synthesis were studied in purified lymphocyte cultures for 20 children with congenital rubella and 18 healthy children (seven susceptible and 11 immune to rubella). Lymphocyte transformation after phytophemagglutinin stimulation was significantly lower in children with congenital rubella as compared to healthy controls. Responses to purified rubella virus were absent in the susceptible controls and absent or at least two times lower in congenital rubella children than in immune controls. After purified rubella virus stimulation, leukocyte migration inhibition factor production was detected in all immune controls, but in none of the susceptible controls, or the congenital rubella-infected children. The results varied with gestational age of intrauterine infection: the impairment of cellular immune response, both after phytohemagglutinin or rubella virus stimulation, was more severe in the children infected in the first two months than in the latter stages of gestation.