This study was performed to determine the effects of environmental 
 tobacco smoke (ETS) on nitric oxide (NO) and immunoglobulin (Ig) production in 
 a murine model of allergic bronchopulmonary aspergillosis (ABPA). Adult 
 BALB/c mice were exposed to aged and diluted sidestream cigarette smoke 
 from day 0 through day 43 to simulate “second-hand 
 smoke”. During exposure, 
 mice were sensitized to soluble Aspergillus fumigatus (Af) 
 antigen intranasally 
 between day 14 and 24. All Af sensitized mice in ambient air (Af + AIR) made 
 elevated levels of IgE, IgG1, IgM, IgG2a and IgA. Af sensitized mice housed in 
 ETS (Af + ETS) made similar levels of immunoglobulins except for IgE that was 
 significantly reduced in the serum and bronchoalveolar lavage (BAL). However, 
 immunohistochemical evaluation of the lung revealed a marked accumulation of 
 IgE positive cells in the lung parenchyma of these Af + ETS mice. LPS stimulation 
 of BAL cells revealed elevated levels of NO in the Af + AIR group, which was further 
 enhanced in the Af+ETS group. In vitro restimulation of the BAL cells on day 45 
 showed a TH0 response with elevated levels of IL3, 4, 5, 10 and IFN-γ. However, 
 by day 28 the response shifted such that TH2 cytokines increased while 
 IFN-γ decreased. The Af + ETS group showed markedly reduced levels in all 
 cytokines tested, including the inflammatory cytokine IL6, when compared to 
 the Af+AIR group. These results demonstrate that ETS affects ABPA by further 
 enhancing the NO production and reduces 
 the TH2 and the inflammatory cytokines while altering the pattern of IgE responses.

Brian W. P. Seymour

Janice L. Peake

Kent E. Pinkerton

Viswanath P. Kurup

Laurel J. Gershwin

Second-hand Smoke Increases Nitric Oxide and Alters the IgE Response in a Murine Model of Allergic Aspergillosis

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune             disease leading to immunological aberrations and excessive multiple autoantibody             production. The aim of this study was to investigate the prevalence of             multiple autoantibodies in SLE patients utilizing the multiplex system method.We analyzed the presence of elevated titers of anti-Ro, anti-La, anti-RNP,             anti-Sm, anti-Jo1, anti-centromere, anti-Scl-70, anti-histone, and anti-dsDNA             antibodies in 199 serum samples (113 SLE patients, 86 healthy donors). We             compared the type, level and number of autoantibodies and the correlation             between             the autoantibody profile and disease severity utilizing the SLEDAI score.Elevated titers of at least one autoantibody were detected in 48% of 42 SLE             patients. Elevated titers of anti-Ro antibodies were most commonly detected. The             distribution of specific autoantibodies was: anti-Ro- 23.8%, anti-dsDNA- 19%,             anti-histone- 19%, anti-RNP- 14.2%, anti-La antibodies- 11.9%, anti-Sm- 7.1%,             anti-Scl 70-4.7%, and anti-centromere- 2.4%. Utilizing ROC analysis, the sensitivity             and specificity of anti-DNA antibodies at a cutoff value of 34 IU/ml were 87.1% and             79.4% respectively. Elevated titers of anti-Jo1 antibody were not detected. There             was a correlation with the titer of anti-Ro antibodies and disease activity by the             SLEDAI score. Seven patients harbored one autoantibody only, 15 patients             harbored 2-3 autoantibodies, 3 patients harbored 4-5 autoantibodies, and one             patient harbored 6 autoantibodies. A correlation between the number of             autoantibodies per patient and disease severity was found. One patient with             a multitude of             autoantibodies had severe lupus and a myriad of clinical manifestations.In conclusion, the multiplex system is specific and sensitive, provides             an autoantibody profile in a single test, and may be useful as a diagnostic             test for SLE. Elevated anti-Ro antibodies are associated with             severe disease. An autoantibody load may be indicative of more severe disease.

Gisele  Zandman-Goddard

Boris  Gilburd

Ora  Shovman

Miri  Blank

Svetlana  Berdichevski

Pnina  Langevitz

Yehuda  Shoenfeld

The Homogeneous Multiplexed System-a New Method for Autoantibody Profile in Systemic Lupus Erythematosus

Specific functional properties of dendritic cells (DCs) have been suspected 
            as being responsible for the impaired specific immune responses observed in 
            human neonates. To analyze stimulatory requirements for the critical transition 
            from immature, antigen-processing DCs to mature, antigen-presenting DCs, we 
            investigated the effect of different proinflammatory mediators and antigens on 
            phenotype and cytokine secretion of human neonatal DCs derived from 
            hematopoietic progenitor cells (HPCs). Whereas single proinflammatory 
            mediators were unable to induce the maturation of neonatal DCs, various 
            combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation 
            of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. 
            Combinations of proinflammatory mediators also increased cytokine secretion 
            by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to 
            be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In 
            conclusion, neonatal DCs can be stimulated to express maturation as well as 
            costimulatory surface molecules. However, induction 
            of maturation requires combined stimulation with multiple proinflammatory signals.

Doreen Krumbiegel

Jan Rohr

Peter Schmidtke

Markus Knuf

Fred Zepp

Claudius U. Meyer

Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

Mechanisms underlying in vitro immunomodulatory effects of polycyclic 
 aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were 
 investigated in harbor seal peripheral leukocytes, via real-time PCR. We examined 
 the relative genetic expression of the protein tyrosine kinases 
 (PTKs) Fyn and Itk, 
 which play a critical role in T cell activation, and IL-2, a cytokine of central 
 importance in initiating adaptive immune responses. IL-1, the macrophage-derived
 pro-inflammatory cytokine of innate immunity, was also included as a measure 
 of macrophage function. Harbor seal PBMC were exposed to the prototypic 
 immunotoxic PAH benzo[a]pyrene (BaP), 3,3',4,4',5,5'-hexachlorobiphenyl 
 (CB-169), a model immunotoxic PCB, or DMSO (vehicle control). Exposure of 
 Con A-stimulated harbor seal PBMC to both BaP and CB-169 produced 
 significantly altered expression in all four targets relative to vehicle controls. The 
 PTKs Fyn and Itk were both up-regulated following exposure to BaP and CB-169. 
 In contrast, transcripts for IL-2 and IL-1 were decreased relative to controls by both
 treatments. Our findings are consistent with those of previous researchers working 
 with human and rodent systems and support a hypothesis of contaminant-altered
 lymphocyte function mediated (at least in part) 
 by disruption of T cell receptor (TCR) signaling and cytokine production.

Jennifer C. C. Neale

Thomas P. Kenny

Ronald S. Tjeerdema

M. Eric Gershwin

PAH- and PCB-induced Alterations of Protein Tyrosine Kinase and Cytokine Gene Transcription in Harbor Seal (Phoca Vitulina) PBMC

Background: There are several mechanisms to describe allergic drug  reactions yet the methods to diagnose them are limited.Objective: To compare several conventional clinical and laboratory  methods to diagnose skin reactions to drugs  to a new method of diagnosing drug reactions by the CellScan system.Methods: The study entailed 21 patients who were diagnosed as  suffering from drug eruptions, and 105 healthy controls with no history of drug  allergy. The drugs were classified into two groups according to suspicion of  causing drug allergy: high and low. Most of the patients were on more than  one drug, leading to 41 patient-drug interactions (assays). Histamine  releasing test (HRT), interferon (INF)-&#947; releasing test and CellScan  examination were performed on lymphocytes of the patients and controls.Results: The HRT was interpreted as positive in 9 out of 18 (50%)  patients and in 13 out of 35 (37%) assays. Based on the INF-&#947; releasing test,  positive results were observed in 16 out of 21 (76%) patients and in 24 out of 41  (59%) assays. In the CellScan test (CST), positive results were observed in 17  out of 21 (81%) patients and in 29 out of 41 (71%) assays. The rate of identifying  the drug for eruption in the high suspicion level drugs was 9 out of 22 (41%)  assays in the HRT, 20 out of 24 (83%) assays in the INF-&#947; releasing test, and 21  out of 24 (87%) studies with the CellScan method. The rate of determining of  the drug that caused the eruption in the low suspicion level drugs was 4 out of  13 (31%) in the HRT, 4 out of 17 (24%) assays in the INF-&#947; releasing test, and 8  out of 17 (47%) analyses in the CST. When examined  in the CellScan, 99 out of 105 (94%) controls were interpreted as negative.Conclusion: This preliminary study indicates that the CellScan seems to  be an easy and promising method for the detection of drugs responsible for  adverse skin reactions. In contrast to the HRT and to the Interferon-&#947; secretion  test, the CellScan method is characterized by its ability to track and monitor  the reaction of individual cells. By measuring the kinetic parameters of selected  cells before and after adding the suspected drug, we were able to identify  the culprit drug. The CellScan method had the highest sensitivity, and the  interferon-&#947; secretion test had the highest specificity for detection of the culprit  drug. In contrast, the analysis of 105  normal control sera disclosed a high specificity of 94% for the CellScan method.

Ilan  Goldberg

Martine Szyper Kravitz

Shmuel  Kivity

Berta  Ben Chaim

Tirza  Klein

Yael  Schiffenbauer

Ela  Trubniykovr

Sarah  Brenner

A Novel System to Diagnose Cutaneous Adverse Drug Reactions Employing the Cellscan&#8212;Comparison with Histamine Releasing Test and Inf-&#947; Releasing Test

p56lck is involved in the maturation of T-cells from double negative 
 (DN) into double positive (DP) T-cells. The objective of this experiment was to 
 determine changes in the levels of thymic and splenic T-cell 
 p56lck using Western
 immunoblotting, along with the proportion and number of T-cell subsets in thymus, 
 spleen and blood using flow cytometry in growing Sprague-Dawley rats. Thymic 
 p56lck levels were negatively correlated with age
 (r=-0.42, 
 p=0.04) and positively 
 correlated with age in the spleen (r=0.50, p=0.01). 
 Nine-week-old rats had 
 a higher percentage of thymic DN and CD8 cells with fewer DP cells compared 
 to younger rats. There were minor differences in the proportions of T-cell subsets 
 in the spleen and blood. T-cell numbers remained proportional to body weight in 
 the lymphoid organs; however, the lower absolute number of 
 T-cells in the younger rats might indicate that they are less able to respond to antigens.

Heather J. Hosea

Edward S. Rector

Carla G. Taylor

Age-related Changes in p56lck Protein Levels and Phenotypic Distribution of T Lymphocytes in Young Rats

Platelet activity and platelet-endothelial cell interactions are important in  the acute development of thrombosis, as well as in the pathogenesis of  cardiovascular disease. An increasing number of foods have been reported to  have platelet-inhibitory actions, and research with a number of flavanol-rich foods,  including, grape juice, cocoa and chocolate, suggests that these foods may provide  some protection against thrombosis. In the present report, we review a series of in  vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation  and platelet-dependent primary hemostasis. Consumption of flavanol-rich cocoa  inhibited several measures of platelet activity including, epinephrine- and  ADP-induced glycoprotein (GP) IIb/IIIa and P-Selectin expression, platelet  microparticle formation, and epinephrine-collagen and ADP-collagen induced  primary hemostasis. The epinephrine-induced inhibitory effects on GP IIb/IIIa and  primary hemostasis were similar to, though less robust than those associated with  the use of low dose (81 mg) aspirin. These data, coupled with information from  other studies, support the concept that flavanols present in  cocoa and chocolate can modulate platelet function through a multitude of  pathways.

Debra A. Pearson

Roberta R. Holt

Dietrich  Rein

Teresa  Paglieroni

Harold H. Schmitz

Carl L. Keen

Flavanols and Platelet Reactivity

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Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.

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Chief Editor, Professor Holland, has a background focusing on researching the development of conjunctival fibrosis and the characterisation of immune responses to potential C. trachomatis vaccine candidates.

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Journal of Immunology Research - Table of contents 2005

title

Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.

Journal of Immunology Research