Peripheral immune cell markers in children with recurrent respiratory infections in the absence of primary immunodeficiency.

The immune system of a child has a degree of immaturity that is maintained until 6-7 years of age. Immaturity may be due to age-related functional disorders in the immune response. A healthy child can contract a series of infections which contribute to the maturation of the immune system during the pre-pubertal period. If repeated infections with prolonged or severe complications occur during childhood, the presence of an immunodeficiency should then be considered. Much more frequent than primary immunodeficiency are recurrent infections (frequently involving the upper respiratory tract), which are less severe and occur under the conditions of an immune system with no apparent major defects. A child can present with 4 to 8 episodes of respiratory infections within a year, during the first 5 years of its life. The average duration of infection is 8 days and up to 2 weeks; if the child presents with 3 episodes of acute infections over a period of 6 months, the respiratory infections are then considered recurrent. The aim of this study was to identify the immunological changes or deviations that cause this clinical syndrome in children. For this purpose, 30 children with recurrent respiratory infections and 10 healthy children were included. Immunoglobulin levels were examined and immunophenotyping was performed. We found that the serum immunoglobulin levels were in the normal range in 70% of the children. On the contrary, our data revealed changes in peripheral cell populations, the most important being the decrease in the T-cluster of differentiation (CD)8+ and total B cell percentages and the increase in the number of memory B cells. The data obtained herein indicated that the decrease in the number of total B cells was mainly due to the decrease in the number of naive IgD+ B cells. On the whole, the findings of this study indicate that recurrent respiratory infections may be associated with an altered cellular immune response. In such situations, the investigation of immunological parameters, such as T and B cell subtypes could complete the clinical diagnosis and guide the treatment strategy, thus increasing the quality of life of patients.

Natural killer cell monitoring in cutaneous melanoma - new dynamic biomarker.

Melanoma is responsible for most skin cancer deaths in humans. The immune system plays a major role in regulating tumor cell proliferation by initiating defence responses against tumor aggression. Research on murine cancer models allow for a better understanding of immune response in malignancies, revealing specific changes of the immune status in the presence of tumors. Melanoma resistance to conventional therapies and its high immunogenicity justify the development of new therapies. These features reinforce melanoma as a suitable model for studying antitumor immunity. Recent findings on NK cell activation in cancer patients indicate that several important parameters, such as tumor capacity to modulate the function and phenotype of NK cells, require consideration for the choice of an NK-based therapy. In this study, we investigated T-CD4+ and T-CD8+ lymphocytes, B lymphocytes and NK cells in peripheral blood and spleen cells suspension from melanoma-bearing mice compared to healthy controls in order to assess the potential for tumor growth-promoting immunosuppression. Our results indicate that in a melanoma-bearing mouse model the percentage of NK cells in spleen is reduced and that their phenotype is different compared to control mouse NK cells.

Phenotypic changes of lymphocyte populations in psoriasiform dermatitis animal model.

Psoriasis is a T cell mediated, chronic inflammatory autoimmune skin disease that affects up to 2-3% of the global population and leads to a decrease in quality of life. Experimental data accumulated in recent years highlighted the important role played by the immune system in the pathogenesis of this disease. Non-human psoriasis models are an important research tool that attempts to reproduce the clinical features of the disease in order to explain the pathogenesis of psoriasis and to identify possible therapeutic targets. Imiquimod-based murine model of psoriatic dermatitis is an alternative to traditional models of experimental psoriasis in mice and the induced dermatitis closely mimics the pathologic changes in human psoriasis. In order to emphasize changes in immune cell populations involved in lesion pathogenesis, we performed a murine model of psoriasiform dermatitis model by topical IMQ application. The progress and the severity of IMQ-induced skin inflammation were clinically (PASI score) and histopathologically evaluated. The immunological changes induced by IMQ treatment in lymphocyte populations from peripheral blood and spleen were evaluated by flow cytometry. The main changes observed in peripheral blood were the significantly increased T-CD8a+ lymphocyte and NK1.1+ cell percentages and the decreased T-CD4+ and B lymphocyte percentages in IMQ-treated mice. In spleen samples, lymphocytes showed the same tendency of variation as in peripheral blood, but without statistical significance. A significant decrease of B cells percentages was observed in spleen suspensions. Data obtained in skin samples may suggest the involvement of CD3ε+, CD4+ and CD8a+ cells in the lesional process. This murine model was analyzed by performing a basic cellular profile at three levels: peripheral blood, spleen and skin. The evaluation aimed to establish the immune framework of this experimental model that could further be used for etipathogenic mechanism identification and/or for studies regarding targeted therapies.

Immunological investigations in prostatic pathology--a prospective study.

BACKGROUND: BPH with prostatitis represents one of the most common urological pathologies affecting most men. The etiology of both conditions remains at the discretion of the various assumptions. OBJECTIVES: The body's cellular immune response in prostate adenoma is a less studied aspect which we have focused on, in this paper. The correlation with a wide range of information from specific investigations such as prostate-specific antigen (PSA) and total histopathology was the secondary aim of this work. METHODS: The study included 31 patients who underwent surgery for prostate adenoma (TUR-P, simple prostatectomy) between 08.2013 and 03.2014. Patients presenting urinary tract infection were excluded from the study. Preoperative evaluation of the immunological examination consisted of lymphocyte immunophenotyping (T, B, NK cells) from peripheral blood performed by flow cytometry. Total PSA was performed in serum by enzyme immunoassay EIA. RESULTS: In all forms of anatomoclinical BPH we found the presence of two major cellular changes: decrease of suppressor/cytotoxic T-cells and decrease of B cells. These deficits may confer an increased susceptibility to viral infection and tumor transformation. NK cells were grown in BPH associated with inflammation. PSA-prostate specific antigen values were grown at less than 50% of the patients in all clinical forms of BPH.

Effects of menadione, hydrogen peroxide, and quercetin on apoptosis and delayed luminescence of human leukemia Jurkat T-cells.

Menadione (MD) is an effective cytotoxic drug able to produce intracellularly large amounts of superoxide anion. Quercetin (QC), a widely distributed bioflavonoid, can exert both antioxidant and pro-oxidant effects and is known to specifically inhibit cell proliferation and induce apoptosis in different cancer cell types. We have investigated the relation between delayed luminescence (DL) induced by UV-laser excitation and the effects of MD, hydrogen peroxide, and QC on apoptosis and cell cycle in human leukemia Jurkat T-cells. Treatments with 500 µM H2O2 and 250 µM MD for 20 min produced 66.0 ± 4.9 and 46.4 ± 8.6% apoptotic cell fractions, respectively. Long-term (24 h) pre-exposure to 5 µM, but not 0.5 µM QC enhanced apoptosis induced by MD, whereas short-term (1 h) pre-incubation with 10 µM QC offered 50% protection against H2O2-induced apoptosis, but potentiated apoptosis induced by MD. Since physiological levels of QC in the blood are normally less than 10 µM, these data can provide relevant information regarding the benefits of flavonoid-combined treatments of leukemia. All the three drugs exerted significant effects on DL. Our data are consistent with (1) the involvement of Complex I of the mitochondrial respiratory chain as an important source of delayed light emission on the 10 µs-10 ms scale, (2) the ability of superoxide anions to quench DL on the 100 µs-10 ms scale, probably via inhibition of reverse electron transfer at the Fe/S centers in Complex I, and (3) the relative insensitivity of DL to intracellular OH• and H2O2 levels.

Regulatory T cells and TH1/TH2 cytokines as immunodiagnosis keys in systemic autoimmune diseases.

We assessed Helper T-cell involvement and possibilities to quantify the cell-based immune response in systemic autoimmune diseases (SAID) in 14 systemic lupus erythematosus (SLE) and 7 rheumatoid arthritis (RA) patients. The goals of investigation were T-CD4+/T-CD8+ ratio, regulatory T cells (Treg) status and TH1/TH2 serum cytokine profiles (IFN-gamma and IL-2, respectively IL-4 and IL-6). SLE group proved significant decreased average Treg value as compared to RA group and controls and showed significant low Treg incidence (86% patients). The distribution of high T-CD4+/T-CD8+ ratio registered no significant distinction among LES and RA groups. SAID patients presented low serum IFN-gamma (86% RA, 60% SLE), high IL-2 (57% RA) and high IL-6 (53% LES), but no significant IL-4 modification. We conclude that Treg percentage remains the only cellular criterion for SAID immune evaluation. In the same time, different secretion mechanisms seem to be involved in SAID, i.e. TH2 in SLE and TH1 in RA.

Prolonged treatment with interferon alpha and peginterferon induces rheumatoid arthritis syndrome and erythema nodosum.

The antiviral treatment of chronic C hepatitis has improved significantly over the past decade with the introduction of interferons (IFNs), and more recently, pegylated IFNs. Up to two-thirds of all patients treated with pegylated IFN combined with ribavirin can now achieve viral eradication if treated according to current guidelines. Despite this success rate, hematological, immunological, rheumatological and dermatological side effects have been reported in chronic hepatitis C patients treated with IFN-alpha. The subjects of this report are two young females with chronic hepatitis C, who developed rheumatoid syndrome and/or erythema nodosum during antiviral treatment with IFN-alpha or pegylated IFN combined with ribavirin.