Immune Phenomena Research Articles

Myocardial infarction secondary to 5-fluorouracil: Not an absolute contraindication to rechallenge?

5-fluorouracil (5-FU) is one of the most commonly prescribed che-motherapeutic agents for the treatment of a variety of malignancies.5-FUcardiotoxicityisuncommonbutpotentiallyserious:includingcar-diac arrhythmias, angina/myocardial infarction, ventricular dysfunction,cardiogenic shock, cardiac arrest, and sudden cardiac death [1].Anesti-mated 2–10% of patients exposed to 5-FU will develop cardiovascularcomplications; and patients with known ischaemic heart disease orprior myocardial infarction appear to be at higher risk [2].Proposedmechanismsunderlying5-FUcardiotoxicityincludedirectmyocardial toxicity, thrombogenic effects, immune phenomena andmyocardial ischaemia secondary to coronary artery vasospasm [3].Whilstrechallengewith5-FUisnotgenerallyrecommendedinpatientswith 5-FU cardiotoxicity due to concerns regarding recurrence anddeath: a careful assessment of the risks and benefits of such a rechal-lenge should be carefully conducted [3]. At present no consensus onprophylaxisortreatmentof5-FUcardiotoxicityexists,anddiscontinua-tion of 5-FU with the use of second-line agents is generally preferred.Adjuvant therapy with 5-FU containing chemotherapeutic regimensforms the basis of colon cancer therapy, carrying significant long termbenefits to both recurrence free and overall survival. These benefitsare not insignificant, with reductions in recurrence free and overallsurvival of 40% and 33% respectively, when compared to observationalone [4]. Furthermore, these benefits also remain superior to that ofalternativeagents,suchasRaltitrexed[5].Wedescribethefirstreportedcase of successful 5-FU rechallenge underclosecardiacobservation in apatient with 5-FU induced vasospastic myocardial infarction.A previously well 30 year old male with resected stage III (T4a,N2a) colorectal adenocarcinoma was commenced on 5-FU,leucovorin and oxaliplatin (FOLFOX 6) adjuvant chemotherapy(5- fluorouracil 400 mg/m

CD80 and CD86 costimulatory molecules differentially regulate OT-II CD4⁺ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice.

Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs) derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA) were cocultured with CD4+ T cells derived from OT-II mice's (C57BL6/J-Tg(TcraTcrb)1100Mjb/J) spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU), activation of these cells (flow cytometry), cytokine profile (ELISA), and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

Late Onset Combined Immunodeficiency Presenting with Recurrent Pneumocystis jiroveci Pneumonia.

Late onset combined immunodeficiency (LOCID) is a recently described variant of common variable immunodeficiency (CVID), involving adult patients presenting with opportunistic infections and/or low CD4+ lymphocyte counts. A 36-year-old male with unremarkable past medical history presented with fever, respiratory failure, and lymphocytopenia. He was found to have Pneumocystis jiroveci pneumonia (PJP), subsequently complicated by recurrent hospital-acquired Pseudomonas aeruginosa pneumonia and immune reconstitution phenomena, attributed to restoration of immunoglobulin levels. Clinicians should be aware of LOCID, which could be confused with HIV infection/AIDS or idiopathic CD4 lymphocytopenia. In the English bibliography there is only one case report, where PJP was the initial presentation of CVID (that case would probably be classified as LOCID). Phenomena of immune reconstitution are described in various settings, including primary immunodeficiency, manifesting as temporary clinical and radiologic deterioration and leading to misperceptions of therapeutic failure and/or presence of alternative/additional diagnoses.

PReS13-SPK-1577: 'Asia' - autoimmune (auto-inflammatory) syndromes induced by adjuvants

In the last decades four enigmatic medical conditions were described, all of which were characterized by an hyperactive immune response as well as similar clinical and laboratory manifestations. These conditions, namely siliconosis, the Gulf war syndrome (GWS), the macrophagic myofasciitis syndrome (MMF) and post vaccination phenomena represent environmental factors that may play a role in inducing or aggravating autoimmunity and auto-inflammation. Vaccines, administered to animal and humans, are clearly one of the best achievements of modern medicine and are commonly and safely inoculated to the vast majority of subjects. However in rare occasions vaccines may induce autoimmune or auto-inflammatory conditions both in animals and in humans. These conditions, either defined diseases such as Gullian Barre syndrome or enigmatic ones, have been reported following different vaccines and vaccination protocols. The susceptibility factors and the temporal association between vaccines and these rare immune mediated reactions are yet to be defined, however the similarities between vaccines and infections and the addition of an adjuvant (i.e. alum, squalene etc.) to almost every vaccine are considered major contributors to such adverse events. Perhaps the most evaluated condition is MMF, in which a cause was clearly delineated. MMF is a rare condition caused by deposition of alum, used to adjuvant different vaccines, which bring about an immune mediated muscles disease. Thus, in only a minority of genetically prone, i.e. HLA-DRB1*01 patients, alum may induce this syndrome. Another immune mediated phenomena leading to autoimmune diseases is exposure to silicones (i.e. breast implant). In a large study Fryzek et a.l showed that a group of 1546 patients with silicone breast implants had a statistically significant increase in 16 of 28 investigated symptoms when compared to a group of 2496 women who underwent reduction mammoplasties. Many of these symptoms satisfied several criteria for fibromyalgia and chronic fatigue syndrome, which is congruent with the FDA's finding that there is a statistically significant link between fibromyalgia and ruptured silicone gel implants. A common denominator to each of these four syndromes as well as to various infectious agents is the trigger entailing adjuvant activity (7). Thus, herein we would like to suggest to include these four conditions under a common syndrome entitled the Autoimmune (Auto-inflammatory) Syndrome induced by adjuvants (ASIA). We propose several major and minor criteria that may aid in the diagnosis of this newly defined condition (ASIA).

Next-Generation Sequencing-Based Transcriptome Analysis of Helicoverpa armigera Larvae Immune-Primed with Photorhabdus luminescens TT01

Although invertebrates are incapable of adaptive immunity, immunal reactions which are functionally similar to the adaptive immunity of vertebrates have been described in many studies of invertebrates including insects. The phenomenon was termed immune priming. In order to understand the molecular mechanism of immune priming, we employed Illumina/Solexa platform to investigate the transcriptional changes of the hemocytes and fat body of Helicoverpa armigera larvae immune-primed with the pathogenic bacteria Photorhabdus luminescens TT01. A total of 43.6 and 65.1 million clean reads with 4.4 and 6.5 gigabase sequence data were obtained from the TT01 (the immune-primed) and PBS (non-primed) cDNA libraries and assembled into 35,707 all-unigenes (non-redundant transcripts), which has a length varied from 201 to 16,947 bp and a N50 length of 1,997 bp. For 35,707 all-unigenes, 20,438 were functionally annotated and 2,494 were differentially expressed after immune priming. The differentially expressed genes (DEGs) are mainly related to immunity, detoxification, development and metabolism of the host insect. Analysis on the annotated immune related DEGs supported a hypothesis that we proposed previously: the immune priming phenomenon observed in H. armigera larvae was achieved by regulation of key innate immune elements. The transcriptome profiling data sets (especially the sequences of 1,022 unannotated DEGs) and the clues (such as those on immune-related signal and regulatory pathways) obtained from this study will facilitate immune-related novel gene discovery and provide valuable information for further exploring the molecular mechanism of immune priming of invertebrates. All these will increase our understanding of invertebrate immunity which may provide new approaches to control insect pests or prevent epidemic of infectious diseases in economic invertebrates in the future.

Targeting Epigenetic Mechanisms for Clinical Translation: Enhancing the Efficacy of Tumor Immunotherapies

The ability to evade host immune surveillance is critical for the survival of tumor cells and is correlated with poor clinical outcomes. Many tumor types have been found to downregulate expression of genes involved in antigen production, processing and presentation to evade immune detection. Recent findings suggest that the mechanisms underlying these immune evasion phenomena extend beyond alterations in DNA sequence to include epigenetic modifications of DNA and associated proteins, including hypermethylation of DNA and altered histone acetylation patterns. This review will summarize alterations in antigen presentation machinery identified in malignant cells, epigenetic mechanisms that can be employed in the downregulation of genes relevant for antigen presentation and translational strategies to target these processes to enhance the efficacy of antitumor immunotherapies.

Beneficial Impact of CCL2 and CCL12 Neutralization on Experimental Malignant Pleural Effusion

Using genetic interventions, we previously determined that C-C motif chemokine ligand 2 (CCL2) promotes malignant pleural effusion (MPE) formation in mice. Here we conducted preclinical studies aimed at assessing the specific therapeutic potential of antibody-mediated CCL2 blockade against MPE. For this, murine MPEs or skin tumors were generated in C57BL/6 mice by intrapleural or subcutaneous delivery of lung (LLC) or colon (MC38) adenocarcinoma cells. Human lung adenocarcinoma cells (A549) were used to induce MPEs in severe combined immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2 and/or CCL12, a murine CCL2 ortholog, were administered at 10 or 50 mg/kg every three days. We found that high doses of CCL2/12 neutralizing antibody treatment (50 mg/kg) were required to limit MPE formation by LLC cells. CCL2 and CCL12 blockade were equally potent inhibitors of MPE development by LLC cells. Combined CCL2 and CCL12 neutralization was also effective against MC38-induced MPE and prolonged the survival of mice in both syngeneic models. Mouse-specific CCL2-blockade limited A549-caused xenogeneic MPE, indicating that host-derived CCL2 also contributes to MPE precipitation in mice. The impact of CCL2/12 antagonism was associated with inhibition of immune and vascular MPE-related phenomena, such as inflammation, new blood vessel assembly and plasma extravasation into the pleural space. We conclude that CCL2 and CCL12 blockade are effective against experimental MPE induced by murine and human adenocarcinoma in mice. These results suggest that CCL2-targeted therapies may hold promise for future use against human MPE.

Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis

An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing-remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function-associated antigen (LFA)-1 and very late activation antigen (VLA)-4 were assessed in T cells (CD3(+) CD8(+) , CD3(+) CD4(+) ), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule (PECAM)-1, P-selectin and vascular cell adhesion molecule (VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 (CD3(+) CD4(+) T cells, B cells), VLA-4 (CD3(+) CD8(+) T cells, NK cells), ICAM-1 (B cells) and ICAM-3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 (CD3(+) CD4(+) ) and VLA-4 (CD3(+) CD4(+) , CD3(+) CD8(+) , NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.

Acute Disseminated Encephalomyelitis following Seasonal Influenza Vaccination in an Elderly Patient

Although such occurrences are rare, it should be recognized that certain vaccines might trigger serious neurological immune phenomena such as Guillain-Barre syndrome, seizures, cranial neuropathy, and acute disseminated encephalomyelitis (ADEM). Here we report on an elderly woman with ADEM following seasonal influenza vaccination who recovered after plasma exchange.

Oncogene abnormalities in a series of primary melanomas of the sinonasal tract: NRAS mutations and cyclin D1 amplification are more frequent than KIT or BRAF mutations

Primary malignant melanoma of sinonasal tract is a rare but severe form of melanoma. We retrospectively analyzed 17 cases and focused on the histologic presentation and the expression of c-Kit, epidermal growth factor receptor (EGFR), cyclin D1/Bcl-1, PS100, and HMB45 and searched for BRAF, NRAS, and KIT mutations that are known to be associated with melanoma subtypes, together with amplifications of KIT, cyclin D1, cyclin-dependent kinase 4, MDM2, and microphthalmia-associated transcription factor using quantitative polymerase chain reaction. In most cases (78%), an in situ component was evidenced. Invasive components were composed of diffuse areas of rhabdoid, epithelioid, or spindle cells and, in most cases, lacked inflammatory reaction, suggesting that an immune escape phenomenon probably develops when the disease progresses. EGFR was rarely and weakly expressed in the in situ component of 2 cases. None of the investigated case showed BRAF V600E, but 1 had a D594G mutation. NRAS mutations in exon 2 (G12D or G12A) were found in 3 cases (18%), and a KIT mutation in exon 11 (L576P), in 1, whereas c-Kit was expressed at the protein level in half of the cases. Amplifications of cyclin D1 were evidenced in 5 cases, confirmed in 3 by fluorescence in situ hybridization, but this was not always correlated with protein expression, found in 8 patients (62.5%), 3 having no significant amplification. In conclusion, primary malignant melanoma of sinonasal tract is not associated with BRAF V600E mutations. Instead, NRAS or KIT mutations and cyclin D1 amplification can be found in a proportion of cases, suggesting that primary malignant melanoma of sinonasal tract is heterogeneous at the molecular level and should not be sensitive to therapeutic approaches aiming at BRAF.

Cord factor (trehalose 6,6′-dimycolate) forms fully stable and non-permeable lipid bilayers required for a functional outer membrane

Cord factor (trehalose 6,6′-dimycolate, TDM) is the major lipid in the outer membrane of Corynebacteria and Mycobacteria. Although its role is well recognized in the immune response phenomena, its membrane biophysical properties remained largely unexplored and TDM has often been described as a detergent. We purified the main components of the outer membrane from Corynebacterium glutamicum and analyzed their membrane forming properties. In mixture with endogenous cardiolipin, but not alone, the spontaneous hydration of TDM produces liposomes. As a pure component, TDM formed vesicles only by the detergent dialysis method. Perdeuterated cardiolipin–TDM mixtures were shown by deuterium nuclear magnetic resonance (NMR) to exhibit a gel to liquid crystalline phase transition over a 273–295K temperature range, for cells grown at 303K, and thus to be in a liquid crystalline state at physiological temperature. Molecular dynamics simulations of hydrated TDM bilayers provided the trehalose average orientation and conformation, the chain order parameters, the area per lipid and the bilayer thickness which was confirmed by electron microscopy. Finally the Porin A–Porin H ion channel from the Corynebacterial outer membrane was reconstituted in TDM liposomes. With properly mycoloylated proteins, it manifested the typical voltage dependent ion channel properties of an outer membrane porin.

Features of Clinical Phenotypes of Food Allergy Syndrome of Cross-reactivity

In recent years a great attention is paid to the study of such an immune phenomenon, as a syndrome of cross-reactivity. It is already proved that often the clinical manifestations of food allergy are not linked to the product of the power supply, but can be caused by pollen of plants. The possibilities of modern diagnostics allow us not only to determine the type of sensitization, but also identify the «guilty» protein allergen-trigger. This article discusses the possible clinical manifestations of food allergy, due to the cross-reactions as between related, and taxonomically not related allergens. The algorithm of forecasting of severity of clinical reactions, as well as a list of proteins, the most often involved in the reactions of intersection is given.

Insulin resistance and “Lipotoxic Liver Diseases”

An expanded dysfunctional adipose tissue that fails to accommodate, utilise and store as much fat as it should has emerged as the prime mover of the patho physiological sequence that leads to accumulation of fat at ectopic sites – including the liver, in metabolic syndrome and cluster of disorders that include Non alcoholic fatty Liver Disease(NAFLD). Non alcoholic steato hepatitis ( NASH) represent the aggressive subset of NAFLD that can progress to cirrhosis . Insulin is the key driver of metabolic homeostasis, particularly glucose flux across cell membrane – a phenomenon that have connotations for survival and evolution of the organism. An impaired sensitivity to insulin action at the adipocyte level is a characteristic biological event in metabolic syndrome. ,7 The associations of Insulin resistance(IR) with metabolic syndrome is nearly universal – so that the two often have interchangeable pathophysiological inferences, a classical example being type 2 diabetes and the other example is NAFLD/NASH. IR through metabolic syndrome is the template that provide a point of convergence for linked clinical conditions diabetes, obesity, dyslipidemia, hypertension and NAFLD/NASH. IR needs to be conceptualised not as a fixed cellular event – exerting an all or none effect like many biological processes, rather as a dynamic and regulated physiological response to a host of environmental factors and triggers including inflammation. IR possibly challenges energy homeostasis, nutrient availability and handling and connects metabolism with immune phenomenon. 12 There are different methods for measurement of IR, of which HOMA-IR is the simplest and the most widely used one in clinical and epidemiological studies. Ever since its’ initial descriptions, NAFLD has been strongly correlated with obesity; body mass index (BMI) has been the most widely used marker of adiposity in clinical studies. Large epidemiological studies on prevalence of fatty liver have also demonstrated this association , while other studies on the impact of BMI on health outcomes have upheld the connection between BMI , socio economic affluence and overall mortality in a population. BMI has been an independent predictor of fat infiltration in the liver with increasing BMI being associated with increased prevalence of NASH in subjects with NAFLD. Ethnic and racial differences in body composition suggest that Asians( Indians , more specifically): a) Have a lower BMI in general as compared to Caucasians yet , b) Have an increased percentage of body fat as well as a higher proportion of fat in the visceral fat(VF) compartments, c) Are predisposed to metabolic abnormalities and adverse health outcomes at a comparatively lower BMI. The signifcance of these observations is the shift of spotlight on waist circumference as a more meaningful and relevant measure of body composition. It soon became evident that a subset of non overweight (BMI<25 ) individuals do have NAFLD along with metabolic syndrome related metabolic dysfunction including diabetes. ,25,26 This entity, “lean” NAFLD, has subsequently been shown to be a distinct phenotype , described primarily amongst Asians – particularly Indians although it has been reported from occidental populations subsequently. Since fatty liver, NASH and even cirrhosis have been shown to occur with subtle anthropometric markers of obesity and a spectrum of metabolic

Immune phenomena in neonates of women with depression during pregnancy: a case-control study

Objective: To evaluate the effects of major and minor depression during pregnancy on the maternal and neonatal immunities. Methods: Peripheral venous blood from depressed women and cord venous blood from their neonates taken simultaneously and immediately after parturition were used. The serum levels of immunoglobulins IgG, IgM and IgA and complements C3 and C4 were determined through single radial immunodiffusion with the kits manufactured by the Biogen company (Mashhad, Iran). To reduce error, all the ring diameters were measured by one experimenter unaware of the study groups. The blood leukocyte and lymphocyte counts and lymphocyte percentage were determined with a H1 counter and for more accuracy also with a Hycel counter. Results: The immune parameters of depressed women were not significantly different from controls. The lymphocyte counts in neonates of women with major and minor depression were increased, whereas ratio of the cord blood level of IgG to the maternal blood level of IgG in neonates of women with major depression were decreased compared to controls. Conclusions: Major depression during pregnancy reduces the prenatal transfer of IgG from mother to neonate. The low prenatal transfer of IgG may have clinical significance, because it can compromise immune competence in neonates.

The intracellular progesterone receptor regulates CD4+ T cells and T cell-dependent antibody responses

Pg has distinct immunomodulatory properties involved in poorly understood immune phenomena, including maternal tolerance of the fetus, increased risk of certain infections during pregnancy or after Pg birth control, and pregnancy-associated remission of autoimmune disease. Several potential mechanisms have been identified, including alteration of Th1 and Treg activity, but the precise cellular and molecular targets of Pg immunomodulation in vivo remain obscure, partly because Pg can signal through several different receptor types. One such receptor, the iPR, encoded by the pgr gene, is essential for reproduction in female mice and is expressed in the thymus and CD4(+) T cells. We hypothesized that iPR regulates CD4(+) T cell activity and adaptive immune responses in vivo. With the use of iPR KO mice, we demonstrate that iPR specifically suppresses TD antibody responses, primarily by dampening CD4(+) Teff activity, likely via transcriptional repression of the IFN-γ gene and modulation of other programs regulating CD4(+) T cells. Our results highlight a novel mechanism linking the endocrine and immune systems, and they offer insight into important but poorly understood phenomena in women's health and autoimmunity.

A shortcut mechanism of innate immune defense by a solitary PRR

Event Abstract Back to Event A shortcut mechanism of innate immune defense by a solitary PRR Jeak Ling Ding1* 1 National University of Singapore, Biological Sciences, Singapore The accepted paradigm about an innate immune response is a multi-stepped process - from recognition of the invading microbe by pathogen-recognition receptors (PRRs) to signal transduction, to the production of antimicrobial effectors by the immune cells. Contrary to this belief, we found that a PRR can act singly via a direct shortcut process, bypassing multiple cascades of reactions. We showed that the extracellular hemoglobin (Hb) acts as a solitary frontline defense PRR, directly recognizing pathogens and eliciting powerful antimicrobial potencies. This innate immune response phenomenon is evolutionarily entrenched for 500 million years, from the limulus to humans. While the invading microbe cleaves the cell-free hemoglobin to extract an iron-rich meal for its survival and further invasion, the host exploits the intruding microbe’s proteases and PAMPs to produce toxic reactive oxygen species (ROS) that effectively kills the pathogen. In this process, the hemoglobin structure-function is rapidly reprogrammed to expose multiple dual antimicrobial activities and its redox reactivity is subsequently suppressed by plasma antioxidants, thus protecting the host from ROS-induced cytotoxicity. Furthermore, we demonstrated that the monocytes efficiently import the redox active Hb via a (a) novel endocrine loop of CD163 receptor recycling and (b) paracrine communication with vascular endothelial cells. Acknowledgements We thank the MoE and A*STAR BMRC for financial support. References Jiang N, Tan NS, Ho B and Ding JL. Respiratory protein-generated reactive oxygen species as an antimicrobial strategy. Nature Immunology 8 (2007): 1114-1122 Du RJ, Ho B and Ding JL. Rapid reprogramming of haemoglobin structure-function exposes multiple dual-antimicrobial potencies. EMBO J 29 (2010): 632-642 Bahl N, Du R, Winarsih I, Ho B, Tucker-Kellogg L, Ho B and Ding JL. Delineation of LPS-binding sites of hemoglobin - from in silico predictions to biophysical characterization. J. Biol. Chem 286 (2011): 37793-37803. Du R, Winarsih I, Ho B and Ding JL. Lipid-free apolipoprotein A1 exerts an antioxidative role against cell-free hemoglobin. Am. J. Clin. Exp. Immunol. 1 (2012): 33-48. Subramanian K, Du RJ, Tan NS, Ho B and Ding JL. CD163 and IgG co-defend against cytotoxic hemoglobin via autocrine and paracrine mechanisms. J. Immunol. (in press) Keywords: Innate immune defense, Pathogen pattern-recognition receptors (PRRs), Hemoglobin, Reactive Oxygen Species, Host-Pathogen Interactions Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Ding J (2013). A shortcut mechanism of innate immune defense by a solitary PRR. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00433 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 Apr 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Jeak Ling Ding, National University of Singapore, Biological Sciences, Singapore, 117543, Singapore, dbsdjl@nus.edu.sg Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jeak Ling Ding Google Jeak Ling Ding Google Scholar Jeak Ling Ding PubMed Jeak Ling Ding Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The Expression and Significance of CD4 +T Lymphocyte in the Peripheral Blood of Patients with Asthma

Objective: To detect the CD4 +T lymphocyte proportion in the peripheral blood of the patients with bronchial asthma at different stages by flow cytometry. Methods: 53 patients with asthma were recruited and divided into three groups: the acute exacerbation group of 28 cases, the mild remission group of 20 cases and the moderate to severe remission group of 5 cases. At the same time, the normal controlled group of 16 cases was set up as contrast. The proportion of Th1, Th2, Th17 and Treg in the peripheral blood of the patients with asthma and normal controlled cases were detected by flow cytometry respectively. Lung function tests were simultaneously performed in the patients with asthma groups and normal controlled group. High-resolution CT was taken in the remission and the normal group, then the ratio of 2 airway wall thickness to outer diameter (2T/D), the ratio of wall area to total airway area (WA%), lung densities in both the inspiratory and expiratory phases and the two phase difference were measured in everyone who took the HRCT. Results: The acute group had a much lower Th1 and Treg proportion than the mild remission group and the normal group (P<0.05), and the remission group also had a lower proportion than the normal controlled group (P<0.05), but the Th1 and Treg proportion difference was not statistically significant between the two remission groups; The proportion of Th2 and Th17 in peripheral blood in acute group was higher than that in the mild remission group and the normal group (P<0.05), and that in the two remission group was also higher than that in the normal group (P<0.05), the proportion of Th2 in the acute group was higher than that in the moderate-severe remission group, but Th17 was not statistically significant between the two groups, the proportion of Th17 in the moderatesevere remission group was higher than that in the mild remission group, but Th2 was not different between the two groups; The ratio of Th1, Th2 and the ratio of Th17, Treg was obviously significant between the acute group, the mild remission group and the normal group (P<0.01), the ratio of Th17 and Treg between any two groups was statistically significant (all P<0.05), whereas the ratio of Th1 and Th2 was not significant between the mild remission group and the moderate to severe remission group, but it was also significant among the other two groups; 2T/D, WA%, expiratory phase CT values and the different CT values between inspiratory phase and expiratory phase were statistically significant among the two remission and the normal groups (P<0.05), but inspiratory phase CT value in the three groups showed no significant difference. Conclusions: There were CD4 + T lymphocyte immunological function disorders in peripheral blood of patients with acute exacerbation and remission of asthma, of which Th2 and Th17 had an enhanced immune response phenomenon, with an obviously enhanced expression for Th17 cells in moderate-severe remission asthma patients, However, Th1 and Treg cells with a protective effect had a lower functioning. Therefore there existed not only Th1/ Th2 imbalance but also Th17/Treg imbalance in peripheral blood of asthma; airway wall thickness pathological changing phenomenon and gas retention phenomenon existed in asthmatic patients too; the diffusion capacity of patients with bronchial asthma and the normal controlled group did not be obviously different.

Gender specific immune status differences in children and adults

Event Abstract Back to Event Gender specific immune status differences in children and adults Julia Lagereva1* 1 Clinical and Diagnostic Centre, Institute of immunology and physiology of the Ural branch of Russian Academy of Sciences, Russia 150 healthy children 7 months-18 years and 45 adults 25-45 years of age balanced by sex were studied to identify gender specific immune status differences dependent from sex hormone concentrations. As result of study it was found that up to 14 years of age the major gender-dependent difference was found among innate immunity phenomena: higher efficacy of phagocytic leucocytes was identified in males. The level of phagocytic activity was correlated with serum progesterone concentration. In older age groups: adolescents 15-18 years and adults the adaptive immunity parameters demonstrated gender-specific differences.Th1 lymphocytes absolute count was increased in male adolescents 15-18 years of age and was correlated with dehydroepiandrosterone sulfate level. Th2 lymphocytes level was significantly higher in females than in males and was correlated with estradiol concentration. IgG and IgM concentrations were higher in adolescent girls and females than in male subjects. Innate and adaptive immunity quantitative factors’ gender-specific differences correlate with changes of sex hormones concentrations. Keywords: immune status, Child Development, Adult, gender differences, T cell subsets Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Lagereva J (2013). Gender specific immune status differences in children and adults. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00049 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Julia Lagereva, Clinical and Diagnostic Centre, Institute of immunology and physiology of the Ural branch of Russian Academy of Sciences, Ekaterinburg, Russia, anna-lagereva@yandex.ru Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Julia Lagereva Google Julia Lagereva Google Scholar Julia Lagereva PubMed Julia Lagereva Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Experimental Murine Fascioliasis Derives Early Immune Suppression with Increased Levels of TGF-β and IL-4

In fascioliasis, T-helper 2 (Th2) responses predominate, while little is known regarding early immune phenomenon. We herein analyzed early immunophenotype changes of BALB/c, C57BL/6, and C3H/He mice experimentally infected with 5 Fasciola hepatica metacercariae. A remarkable expansion of CD19+ B cells was observed as early as week 1 post-infection while CD4+/CD8+ T cells were down-regulated. Accumulation of Mac1+ cells with time after infection correlated well with splenomegaly of all mice strains tested. The expression of tumor necrosis factor (TNF)-α mRNA in splenocytes significantly decreased while that of IL-4 up-regulated. IL-1β expression was down-modulated in BALB/c and C57BL/6 mice, but not in C3H/He. Serum levels of transforming growth factor (TGF)-β were considerably elevated in all mice during 3 weeks of infection period. These collective results suggest that experimental murine fascioliasis might derive immune suppression with elevated levels of TGF-β and IL-4 during the early stages of infection.

Viral load rebound in presumed elite controllers: a small case series of the potential use of non‐prescribed HAART in African patients

IntroductionHIV elite controllers are rare with an incidence of &lt;1/300 [1]. We report 4 cases of presumed elite control with subsequent viral load rebound possibly due to non‐prescribed HAART. Case 1: A 37‐year‐old African woman trafficked to the UK was diagnosed HIV‐positive with viral load (VL) &lt;40 copies/mL and CD4 count of 436 cells/cmm. She denied prior diagnosis and was presumed an elite controller until a rise in VL to 26,5205 copies/mL 6 months later (Table 1). Time from diagnosis CD4 (cells/cmm) Viral load (copies/mL) 0 436 (26%) &lt;40 1 month 424 (18%) &lt;40 3 months N/A &lt;40 6 months 387 (29%) 265,205 6 months 264 (18%) 338,291 A resistance test reported HIV‐1 subtype C with a minor protease inhibitor mutation (A71T). It was subsequently disclosed she was given unidentified tablets by traffickers. Case 2: A 31‐year‐old African woman presented 37 weeks pregnant and was diagnosed HIV‐positive with VL 147 copies/mL and CD4 count of 1065 cells/cmm. She denied prior diagnosis, however stated an African doctor visited her ex‐partner's home and supplied tablets identified as lopinavir/ritonavir and zidovudine/lamivudine. Clinics in this area were contacted but had no record of this patient. There was a rise in VL with a resistance test reporting HIV‐1 subtype C/D with no mutations. Case 3: A 53‐year‐old African woman presented 6 weeks after a sexual assault in her home country and was diagnosed HIV‐positive with VL&lt;40 copies/mL and CD4 count of 609 cells/cmm. She denied prior diagnosis but stated her employers gave her unidentified tablets after the assault. Over 3 months VL increased to 390,751 copies/mL (Table 2). Time from diagnosis CD4 (cells/cmm) Viral load (copies/mL) 0 609 (30%) &lt;40 1 month 763 (29%) &lt;40 2 months N/A 417 4 months 616 (19%) 390,751 6 months 237 (18%) 67,833 A resistance test reported HIV‐1 subtype A with no mutations. Case 4: A 42‐year‐old African man was diagnosed HIV positive with VL 269 copies/mL and CD4 count of 562 cells/cmm. A resistance test reported HIV‐1 subtype B with minor PI and NRTI mutations (L10V and V118L respectively). HIV parameters remained stable until 20 months later with an increase in VL to 1,463,132 copies/mL (Table 3). Time from diagnosis CD4 (cells/cmm) Viral load (copies/mL) 0 562 (33%) 269 3 months 454 (37%) 810 6 months 456 (29%) 1110 9 months 492 (31%) 1013 14 months 473 (27%) 199 20 months 279 (13%) 1,463,132 20 months 299 (12%) 1,070,823 A resistance test excluded super‐infection reporting a similar sequence and no new mutations. Co‐existing pathology was also excluded. He subsequently disclosed taking medication supplied by his family but denied this was HAART.ConclusionThe viral load rebound seen in these cases may be due to a viral or immune mediated phenomenon; however, the possibility of non‐prescribed HAART has to be considered. Home test kits for HIV are widely available and there are reports of counterfeit HAART in the developing world [2]. The HIV community has to be vigilant in reporting cases of this nature which create many anxieties regarding toxicity and resistance.