Activation Of Humoral Immunity Research Articles

Humoral immune activation in amyotrophic lateral sclerosis patients

There is evidence that immunological factors may involved in the pathogenetic mechanisms of amyotrophic lateral sclerosis (ALS). Few studies to date have explored the status of the humoral immune response in patients with ALS. We examined the presence of humoral immune activation in ALS patients, serum immunoglobulins (IgG, IgA and IgM) levels were measured in 36 patients with ALS and 35 normal controls. Serum IgG, IgM and IgA levels were not significantly different in our ALS patients compared with the control group (P=ns). No correlations of serum IgG, IgM and IgA concentrations with duration, severity of the disease or the clinical form of onset (bulbar or spinal) were found in our ALS patients. Our results do not suggest a humoral immune activation in ALS patients. This does not exclude that immunological mechanisms may be involved in ALS pathogenesis.

Impact of cytokines on diffuse splenic 18F-fluorodeoxyglucose uptake during positron emission tomography/computed tomography

Concurrent inflammation or anemia at the time of PET/computed tomography (CT) could be one of several causes of diffuse splenic (18)F-fluorodeoxyglucose ((18)F-FDG) uptake. In this study, we focused on cytokines to investigate interactions during this phenomenon and clarify the significance of splenic (18)F-FDG uptake in PET/CT. We selected 40 patients (17 women and 23 men) with cholangiocarcinoma, pancreatic cancer, or gallbladder cancer who had undergone PET/CT. These patients were subdivided into two groups (group A: patients showing splenic (18)F-FDG uptake exceeding hepatic uptake; group B: patients showing hepatic (18)F-FDG uptake exceeding splenic uptake). Blood sampling was performed for each patient on the same day as PET/CT, and 22 types of cytokines and hematologic indices were analyzed. Group A showed higher levels of interleukin (IL)-1β (P=0.0478), IL-1RA (P=0.0044), IL-4 (P=0.0118), IL-6 (P=0.0375), IL-7 (P=0.0478), and IL-13 (P=0.0081) compared with group B. However, interferon-inducible protein-10 (IP-10; P=0.1714), IL-9 (P=0.8022), IL-8 (P=0.1631), IL-5 (P=0.5273), IL-3 (P=0.3097), IL-23 (P=0.1194), IL-2 (P=0.1099), IL-1α (P=0.4439), IL-17α (P=0.8811), IL-16 (P=0.3201), IL-15 (P=0.0580), interferon-γ (IFN-γ; P=0.5308), growth-regulated oncogene (GRO; P=0.2847), granulocyte macrophage-colony-stimulating factor (GM-CSF; P=0.0913), granulocyte-colony-stimulating factor (G-CSF; P=0.5244), and soluble CD40 ligand (sCD40L; P=0.1714) levels in group A were not statistically significantly different compared with those in the control group. In addition, the white blood cell counts and C-reactive protein levels in group A showed higher values compared with group B. IL-13 among the cytokines and C-reactive protein among the hematologic indices were significant predictors of splenic (18)F-FDG uptake exceeding hepatic (18)F-FDG uptake. This study showed that splenic F-FDG uptake is related to IL-1β, IL-1receptor antagonist, IL-4, IL-6, IL-7, and IL-13. These cytokines may reflect the activation of humoral immunity of the spleen.

Detection of Human Cytomegalovirus (HCMV) among Infertile Male in AL-Najaf governorate.

The current study aimed to detect human cytomegalovirus among infertile individual. Blood and seminal fluid collected of 300 infertile male randomly, ELISA technique was used to know the activity of humoral immunity among them through measuring anti-HCMV IgM and IgG antibodies, the result revealed that 31 (11%) were positive for IgM result and 234 (78%) were positive for IgG. The PCR technique showed that out of 300 samples only 22 (7.4%) gave positive results, In case of control group, results were negative for anti- HCMV IgM antibodies in ELISA test and PCR technique. While IgG gave a weak positive results. Objective: the present study was to study the relationship between the virus and infertility through detection of human cytomegalovirus (HCMV) infection in infertile male in AL-Najaf governorate by screening of anti-human cytomegalovirus IgM and IgG in the serum and detection of human cytomegalovirus DNA in seminal fluid, using PCR technique.

Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. IL-21/IL-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum IL-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) IL-21 in MS and NMO patients still remain unknown. To detect the CSF concentration of IL-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity. CSF IL-21 was detected by an enzyme-linked immunosorbent assay (ELISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16). CSF concentration of the IL-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between IL-21 and complement in NMO cohort (p=0.023) and high IL-21 levels in autoantibody-positive subgroup (p=0.027). The concentration of CSF IL-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO.

Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy

Recently, the disappearance of oligoclonal bands (OCBs) from the cerebrospinal fluid (CSF) of a few natalizumab-treated patients with multiple sclerosis (MS) has been reported. This is interesting since CSF-restricted OCB are believed to persist in MS. We pooled CSF data from 14 MS centers to obtain an adequate sample size for investigating the suspected changes in central nervous system (CNS)-restricted humoral immune activities in the context of natalizumab therapy. In a retrospective chart analysis, CSF parameters of blood–CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy. At the time of repeat lumbar puncture, local IgG production (according to Reibergram) was significantly reduced (p < 0.0001) and OCB had disappeared in 16% of the patients. We therefore conclude that natalizumab therapy interferes with intrathecal antibody production at least in a significant number of patients.

PECULIAR IMMUNOLOGICAL PROPERTIES OF CHRONIC POSTTRAUMATIC OSTEOMYELITIS

A comparative study of cellular immunity parameters was performed in patients with long bone chronic posttraumatic osteomyelitis in regard to osteomyelitis stages. Thirty patients with the fistulous form of long bone chronic posttraumatic osteomyelitis and 13 patients with long bone chronic posttraumatic osteomyelitis in the remission stage were examined using laser flow citometry. It was revealed that a moderate leukocytosis, increased monocyte and neutrophile absolute number as well as increased CD25 and HLA-DR-positive T-lymphocyte number are typical for chronic osteomyelitis regardless of the pathological process stages. The remission stage in patients with chronic posttraumatic osteomyelitis is accompanied by moderate activation of humoral immunity (increased B-lymphocyte (CD19+) number and increased production of IgG). The decrease in the peripheral blood lymphocyte number and well as reduction of HLA-DR expression on monocytes creates prerequisites for the development of fistulous osteomyelitis form and can be an indication for administering the preparations of immunomodulating action.

Female Drosophila melanogaster suffer reduced defense against infection due to seminal fluid components

Reduced defense against infection is commonly observed as a consequence of reproductive activity, but little is known about how post-mating immunosuppression occurs. In this work, we use Drosophila melanogaster as a model to test the role of seminal fluid components and egg production in suppressing post-mating immune defense. We also evaluate whether systemic immune system activity is altered during infection in mated females. We find that post-mating reduction in female defense depends critically on male transfer of sperm and seminal fluid proteins, including the accessory gland protein known as “sex peptide.” However, the effect of these male factors is dependent on the presence of the female germline. We find that mated females have lower antimicrobial peptide gene expression than virgin females in response to systemic infection, and that this lower expression correlates with higher systemic bacterial loads. We conclude that, upon receipt of sperm and seminal fluid proteins, females experience a germline-dependent physiological shift that directly or indirectly reduces their overall ability to defend against infection, at least in part through alteration of humoral immune system activity.

Inflammation and decreased immunoregulation characterize the leptin receptor deficient (db/db) mouse model of type II diabetes. (173.12)

Abstract Type II diabetes is an inflammatory disease marked by chronic immune activation. Our goal is to describe the fundamental distinctions in the immune system of the db/db mouse. Serum was collected for a 58-factor immunoassay. Splenic leukocytes were isolated for six panels of flow cytometry to examine immune subsets and activation states. Db/db mice exhibit higher levels of proinflammatory factors such as C-reactive protein, granulocyte chemotactic protein-2, monocyte chemotactic protein-1, macrophage inflammatory protein-2, IL1α, and T-RANTES and lower levels in regulatory IL10. Flow cytometry data revealed upregulation of the adhesion molecule CD11b on neutrophils, monocytes and macrophages. Macrophages also expressed increased levels of costimulatory molecule CD80. Inflammatory DC were increased while regulatory DC were decreased. Pre-germinal center B cells were decreased. Plasma and memory B cells were increased with an increase in CD22 maturity marker. FoxP3+ T regs were decreased with a reciprocal increase in CD127. Total CD8 T cells were increased with greater naive populations. Unactivated NK cells were increased, and all NK populations had decreased Ly49H and KLRG1. Above results were significant with p&amp;lt;0.05. Baseline immune activation in db/db mice is marked by increased circulating proinflammatory factors, decreased circulating regulatory factors, increased activation of innate and humoral immunity, and suppressed regulatory and cellular immunity.

Construction of an Immunostimulatory Plasmid, pUCpGs10, and Research on its Immune Adjuvant Effect

In order to overcome the instability of CpG ODN in vivo, sequence diversity, and individual differences, eleven CpG ODN fragments were meticulously selected and linked to form a Multi-CpG, which were repeatedly inserted into the cloning vector pUC19 for constructing the recombinant plasmid pUCpGs10 containing ten of Multi-CpG. Using the multi-genotype HCV E1 and multi-epitope complex HCV-T as immunogens, and plasmid pUCpGs10 as the immune adjuvant, Balb/c mice were immunized through nasal and subcutaneous immunization. Strong-specific humoral and cellular immune response were induced, which can obviously inhibit the growth of homograft expressing HCV antigen. The immune adjuvant effect of pUCpGs10 closely matched that of Freund's complete adjuvant. The plasmid pUCpGs10 can significantly improve IgA content in serum and different mucosal extract and systematical T-cell response via intranasal immunization. In conclusions, the newly constructed immunostimulatory plasmid pUCpGs10 is able to effectively activate the humoral and cellular immune activity, and possesses activation on mucosal immune response.

Clinical Significance of Peripheral Blood T Lymphocyte Subsets inHelicobacter pylori-Infected Patients

Background. Helicobacter pylori chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease and vigorous humoral and cellular immune responses. Methods. In order to clarify the immunological changes induced by this infection, we determined the percentage and, as indicated, ratios of the following cells in peripheral blood of 45 H. pylori-infected patients and 21 control subjects: CD4+ T cell, CD8+ T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4+CD25+ T cells, Foxp3+ regulatory T cells (Tregs), CD4/CD8 ratio, and Th1/Th2 ratio. Results. The percentage of CD8+ T cells was significantly lower in H. pylori-infected patients (mean ± SD; 18.0 ± 7.1%) compared to control subjects (mean ± SD; 23.2 ± 7.8%) (P < 0.05). The CD4/CD8 ratio was significantly higher in H. pylori-infected patients (mean ± SD; 3.1 ± 2.4) compared to control subjects (mean ± SD; 2.1 ± 1.0) (P < 0.05). The Th1/Th2 ratio was significantly lower in H. pylori-infected patients (mean ± SD; 10.0 ± 8.5) compared to control subjects (mean ± SD; 14.5 ± 9.0) (P < 0.05). The percentage of CD4+CD25+ T cells in H. pylori-infected patients (mean ± SD; 13.2 ± 6.2%) was significantly higher than that in control subjects (mean ± SD; 9.8 ± 3.4%) (P < 0.05). However, there was no significant difference in Tregs. Conclusion. Tregs did not decrease, but the activation of humoral immunity and Th2 polarization were observed in the peripheral blood of H. pylori-infected patients. In some cases, these changes may induce systemic autoimmune diseases.

Immune Modulation of Atherosclerosis

The notion that inflammation plays a role in atherosclerosis dates to separate observations by Virchow and von Rokitansky in the middle of the 19 th century that atherosclerotic blood vessels contained evidence of cellular inflammation. This concept remained stagnant until the 1970s, when Russell Ross demonstrated that monocyte adhesion to the endothelial surface was an early and essential feature of atherosclerosis.1 These observations, coupled with knowledge that modified low-density lipoprotein (LDL) supports foam cell formation and promotes atherosclerosis disease activity,2 focused early investigative efforts on monocytes and macrophages, the foam cell precursors. Indeed, it is clear that neutrophils3 and monocytes enter lesion-prone arterial sites, the latter differentiate into macrophages, and then take up accumulated LDL-cholesterol to form foam cells and early atherosclerotic lesions. Innate immune responses, such as recognition of modified LDL-derived epitopes via macrophage Toll-like receptors, prompts cytokine-mediated recruitment of other inflammatory cells to the lesion4 that, in turn, promote the adaptive immune responses responsible for the chronic inflammation of atherosclerosis. Emerging evidence has helped to refine this paradigm and identify critical events in adaptive immunity that could represent therapeutic opportunities for immune modulation of atherosclerosis. Activated endothelium is characterized by adhesion molecule expression and reduced barrier function that mediate the recruitment of both monocytes5 and T-cells into lesion-prone sites in the arterial wall. With regard to T-cells, histological examination of atherosclerotic lesions demonstrate the presence of both CD4+ T helper (Th) cells, CD8+ cytotoxic T (Tc) cells, and regulatory T cells (Treg) in lesions, although Th cells generally predominate. Lesional T-cells represent a cellular minority …

Emerging Concepts on the Role of Innate Immunity in the Prevention and Control of HIV Infection

While neutralizing antibodies can provide sterilizing protection from HIV infection via their variable domains, the antibody constant domain provides a functional link between innate and adaptive immunity and offers a means to harness the potent antiviral properties of a wide spectrum of innate immune effector cells. There has been a growing appreciation of the role of these effector mechanisms across fields from cancer immunotherapy to autoimmunity and infectious disease, as well as speculation that this mechanism may be responsible for the protection observed in the RV144 HIV vaccine trial. This review summarizes these extraneutralizing humoral immune activities, progress in defining the importance of these effector mechanisms during progression in HIV infection, and the potential impact that such vaccine-induced immune responses may have on protection from infection.

Anti-Nucleocapsid Protein Immune Responses Counteract Pathogenic Effects of Rift Valley Fever Virus Infection in Mice

The known virulence factor of Rift Valley fever virus (RVFV), the NSs protein, counteracts the antiviral effects of the type I interferon response. In this study we evaluated the expression of several genes in the liver and spleen involved in innate and adaptive immunity of mice immunized with a RVFV recombinant nucleocapsid protein (recNP) combined with Alhydrogel adjuvant and control animals after challenge with wild type RVFV. Mice immunized with recNP elicited an earlier IFNβ response after challenge compared to non-immunized controls. In the acute phase of liver infection in non-immunized mice there was a massive upregulation of type I and II interferon, accompanied by high viral titers, and the up- and downregulation of several genes involved in the activation of B- and T-cells, indicating that both humoral and cellular immunity is modulated during RVFV infection. Various genes involved in pro-inflammatory responses and with pro-apoptotic effects were strongly upregulated and anti-apoptotic genes were downregulated in liver of non-immunized mice. Expression of many genes involved in B- and T-cell immunity were downregulated in spleen of non-immunized mice but normal in immunized mice. A strong bias towards apoptosis and inflammation in non-immunized mice at an acute stage of liver infection associated with suppression of several genes involved in activation of humoral and cellular immunity in spleen, suggests that RVFV evades the host immune response in more ways than only by inhibition of type I interferon, and that immunopathology of the liver plays a crucial role in RVF disease progression.

MP-16.01 Cellular and Humoral Immune System Activation by Sipuleucel-T: Preliminary Data from the OpenACT Phase 2 Trial

Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate an immune response against prostate cancer. It is made from peripheral blood mononuclear cells (PBMCs) cultured ex vivo with a recombinant fusion antigen, PA2024 comprising prostatic acid phosphatase [PAP] linked to granulocyte-macrophage colony-stimulating factor [GM-CSF]). Sipuleucel-T has demonstrated improved overall survival (OS) in men with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC).

7011 POSTER DISCUSSION Cellular and Humoral Immune System Activation by Sipuleucel-T -Preliminary Data From the OpenACT Phase 2 Trial

7011 POSTER DISCUSSION Cellular and Humoral Immune System Activation by Sipuleucel-T -Preliminary Data From the OpenACT Phase 2 Trial

Defining terminally differentiating B cell populations in rainbow trout immune tissues using the transcription factor XbpI

The nature of antibody-secreting cells in the rainbow trout is poorly defined. Here we describe a flow cytometric approach to help differentiate between four major trout B cell subsets present during terminal B cell differentiation: resting B cells, activated B cells, plasmablasts, and plasma cells. To aid in the identification of B cell subsets, the LPS-inducible transcription factor XbpI-S was used as a marker. An antibody specific to the stable form of inducible transcription factor X-box protein I (XbpI) was generated, which detects XbpI-S protein expression for species within the Oncorhyncus genus, including rainbow trout. Combinatorial expression patterns, or B cell signatures, were established using antibodies to XbpI-S, Pax5, and IgM in combination with a proliferation marker. We show that XbpI-S induction in trout splenic B cells increases throughout a 10-day in vitro LPS-induction period and that increased XbpI-S expression correlates with increased HCmu expression in the cell. PBLs displayed a lower level of XbpI-S induction during this incubation period, compared to spleen. We conclude that trout B cells follow a highly conserved B cell activation pathway, albeit slower than what has been observed in mammalian species. The use of XbpI-S as an activation marker for trout humoral immune activation promises to be useful for future in vivo studies, and can be applied to a broad range of teleost species.

Magnetic-lazer modulation of specific humoral immunity in pregnant women with anemia

This article presents the comparative analysis of humoral and cellular immunity indicators under the influence of magneticlaser effect in 2 frequency ranges (150—1 5000 Hz) for treatment of pregnant women with mild anemia against the background of chronic gastritis, associated with contamination gastrointestinal tract Helicobacter pylori. The application of magnetic-laser effect in frequency 150 Hz allows to raise of hemoglobin lowers the titre of antibodies to Helicobacter pylori. The moderate stimulation of Th1 link withoit activation of humoral immunity is optimal in treatment of benign anemia of pregnancy.

Antioxidant effect of Iloprost: current knowledge and therapeutic implications for systemic sclerosis

Many lines of independent research have pointed out the role of oxidative stress as a fascinating pathogenic link between the three main hallmarks of systemic sclerosis (SSc), viz. humoral and cellular immunity activation, microvascular damage and widespread tissue fibrosis. Therefore counteracting oxidative stress may have a favourable impact on clinical features and progression of disease. It is becoming clearer that Iloprost, a synthetic stable analogue of prostacycline, currently employed in the treatment of SSc vascular features, also possess anti-oxidative properties beside its prostaglandin-like vasodilatory and antiaggregant effects. This brief review is aimed to discuss available clinical evidences supporting Iloprost antioxidant action and focus on putative molecular pathways underlying it.

Experimental Study of the Effects of Permafrost Microorganisms on the Morphofunctional Activity of the Immune System

The immunobiological potential of a new microorganism species isolated from permafrost specimens (PMO strain 3M) collected from the Mammoth Mountain in Yakutia was studied in laboratory mice. PMO injected intraperitoneally in doses of 2500 to 50 × 10(6) microbial bodies caused characteristic dose-dependent effects on the structure and functions of the immune system (thymus and spleen indexes, functional activity of splenic macrophages, cellular and humoral immunity). Doses of PMO stimulating functional activities of both cellular and humoral immunity were detected.

Abstract 5508: B lymphocytes are activated during the course of sipuleucel-T treatment, leading to an antigen-specific humoral response

Abstract Introduction: Sipuleucel-T is an autologous cellular immunotherapy FDA approved for men with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC). Previous clinical data have shown that antibodies specific for the immunizing antigen, PA2024, develop within two weeks post-end of sipuleucel-T treatment. Here, we sought to determine whether B lymphocytes were activated during the course of treatment and to evaluate their phenotypic profile in two ongoing clinical studies (NEoACT and PRoACT). Materials and Methods: Sipuleucel-T is manufactured from peripheral blood mononuclear cells (PBMCs) isolated every two weeks by leukapheresis. The PBMCs are cultured with PA2024, an antigen composed of prostatic acid phosphatase (PAP) fused to granulocyte macrophage-colony stimulating factor (GM-CSF), washed, and then infused into the patient as sipuleucel-T. Each patient receives three infusions. The activation status of B lymphocytes was evaluated by multi-color flow cytometry during the manufacture of sipuleucel-T, before and after culture at each of the three treatment times. B lymphocyte subsets were identified by their expression of CD20, IgD and CD27: CD20+IgD+CD27− naive, CD20+IgD+CD27+ mature activated, and CD20+IgD−CD27+ memory. Activation of each of these subsets was determined by their expression of CD80 and CD96. Antigen-specific B lymphocyte function, in the form of antibody production, was evaluated in the serum of sipuleucel-T-treated subjects before and after treatment. Summary: In the mature activated B lymphocyte subset, an increase in the proportion of lymphocytes expressing CD80+ and CD86+ was detected following culture with PA2024, with the increase in CD86+ mature B lymphocytes being the highest after the second infusion of sipuleucel-T. An increase in mature activated B lymphocytes directly ex vivo, pre-culture, was not observed prior to the second or third infusion. Additionally, CD80 and CD86 expression was upregulated on memory B lymphocytes in response to culture with PA2024 and following the first infusion. Furthermore, PA2024- and PAP-specific antibody responses were detected and maintained 2-22 weeks after the completion of sipuleucel-T treatment.Conclusions: These data demonstrate that B lymphocyte activation is a consequence of ex vivo culture with PA2024 and precedes an antigen-specific humoral response, as detected in the patients’ serum after treatment with sipuleucel-T. Collectively, these findings provide evidence of therapy-induced humoral immune activation in men with mCRPC treated with sipuleucel-T. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5508. doi:10.1158/1538-7445.AM2011-5508