Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 3rd International Conference and Exhibition on Clinical & Cellular Immunology Baltimore, USA.

Day 2 :

Keynote Forum

Warren J. Leonard

National Institutes of Health, USA

Keynote: Complex actions of transcription factors in mediating cytokine biology in the immune response

Time : 8:30-8:55

OMICS International Immunology Summit-2014 International Conference Keynote Speaker Warren J. Leonard photo
Biography:

Warren J. Leonard received his A.B. from Princetonand M.D. from Stanford, and now isChief, Laboratory of Molecular Immunology and Director, Immunology Center, NHLBI. Dr. Leonard has received many awards, including the American Association of Immunologists (AAI)-Huang Foundation Meritorious Career Award and the Honorary Lifetime Membership Award of the International Cytokine and Interferon Society. He has more than 300 publications and 19 patents. He is on multiple editorial boards, is past-president of the International Cytokine Society, a member of the Board of the Foundation for Advanced Education in the Sciences, a Fellow of the AAAS, and a member of the Institute of Medicine (IOM) of the National Academies.

Abstract:

Six cytokines (IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21) share the common cytokine receptor  chain, which is mutated in humans with X-linked severe combined immunodeficiency. These cytokines all activate JAK1 and JAK3, and collectively they control a broad range of biological processes within the immune system, in part via their activation of STAT proteins. IL-2, IL-7, IL-9, and IL-15 dominantly activate STAT5A and STAT5B, IL-4 activates STAT6, and IL-21 activates primarily STAT3. IL-2 via STAT5 broadly regulates Th differentiation, promoting Th1 and Th2 differentiation via its induction of IL-12R2 and IL-4R, and inhibiting Th17 differentiation, in part by its repression of Il6st and induction of Tbx21, as well as by potential STAT5 competition with STAT3. IL-2 also promotes Th9 differentiation, which is inhibited by IL-21, and these opposing effects of these cytokines correlate with the repression of BCL6 by IL-2 versus its induction by IL-21. Interestingly, we and others have also shown that STAT3 in combination with IRF4-BATF complexes globally mediate IL-21-dependent transcription as well as Th17 differentiation. These findings underscore the complex contributions of c family cytokines and the multiple STAT proteins they regulate in controlling the immune response.

Keynote Forum

Yehuda Shoenfeld

Tel-Aviv University, Israel

Keynote: ASIA - Autoimmune (Auto-inflammatory) syndromes induced by adjuvants

Time : 8:55-9:20

OMICS International Immunology Summit-2014 International Conference Keynote Speaker Yehuda Shoenfeld photo
Biography:

Yehuda Shoenfeld is the founder and head of the Zabludowicz Center for Autoimmune Diseases, at the Sheba Medical Center which is affiliated to the Sackler Faculty of Medicine in Tel-Aviv University, in Israel. Dr. Shoenfeld is the Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases at the Tel-Aviv University.rnHis clinical and scientific works focus on autoimmune and rheumatic diseases, and he has published more than 1700 papers in journals such as New Eng J Med, Nature, Lancet, Proc Nat Acad Scie, J Clin Invest, J Immunol, Blood, FASEB, J Exp Med, Circulation, Cancer and others. His articles have had over 31,000 citations. He has written more than three hundred and fifty chapters in books, and has authored and edited 25 books, some of which became cornerstones in science and clinical practice, such as \"The Mosaic of Autoimmunity\", \"Infections and Autoimmunity\" and the textbook \"Autoantibodies\" and \"Diagnostic criteria of autoimmune diseases\", all of which were published by Elsevier and sold by the thousands.rnrnHe is on the editorial board of 43 journals in the field of rheumatology and autoimmunity and is the founder and the editor of the IMAJ (Israel Medical Association Journal) the representative journal of science and medicine in the English language in Israel, and also is the founder and Editor of the \"Autoimmunity Reviews\" (Elsevier) (Impact factor 6.6) and Co-Editor of \"Journal of Autoimmunity\" (Impact factor 7.4). For the last twenty years Dr. Shoenfeld has been the Editor of \"Harefuah\" The Israel journal in medicine (Hebrew) and he has edited the Israel Medical Encyclopedia (10 volumes, 5000 items). He had organized over 20 international congresses in autoimmunity. He is the editor-in-chief for Journal of Autoimmunity along with M. Eric Gershwin (University of California, Davis). According to the Journal Citation Reports, the journal has a 2012 impact factor of 8.145, ranking it 11th out of 137 journals in the category \"Immunology”. This journal is a peer-reviewed medical journal covering research on all aspects of autoimmunity. It was established in 1988 and is published 8 times per year by Elsevier.rn

Abstract:

Four enigmatic medical conditions were described recently, all characterized by hyperactive immune response and similarrnclinical and laboratory manifestations. Th ese conditions (siliconosis, Gulf War Syndrome, macrophagic myofasciitisrnsyndrome and post-vaccination phenomena) imply that environmental factors may play a role in inducing or aggravatingrnautoimmunity and auto-infl ammation. In rare occasions vaccines may induce autoimmune or auto-infl ammatory conditionsrnboth in animals and in humans. Th ese conditions - defi ned diseases (Gullian-Barre syndrome) or enigmatic ones - havernbeen reported following vaccines and vaccination protocols. Th e susceptibility factors and the temporal association betweenrnvaccines and these immune mediated reactions remain to be defi ned; however, the similarities between vaccines and infectionsrnand the addition of adjuvants to almost every vaccine are considered major contributors to such adverse events. In MMF arncause was clearly delineated. MMF is a rare condition caused by deposition of alum, an adjuvant in diff erent vaccines, whichrncause an immune mediated muscles disease. In genetically prone patients, alum may induce this syndrome. Another similarrnphenomenon is exposure to silicones. In a study, a group of patients with silicone breast implants had a statistically signifi cantrnincrease in 16 of 28 investigated symptoms consistent with fi bromyalgia and chronic fatigue syndrome criteria, comparedrnto a group of women who underwent reduction mammoplasties, congruent with the FDA’s establishment of a link betweenrnfi bromyalgia and ruptured silicone implants. A common denominator to these syndromes is the trigger entailing adjuvantrnactivity. We suggest including these four conditions in one syndrome, the \"Autoimmune Syndrome Induced by adjuvants\" (ASIA).

  • Track 1: Clinical Immunology
    Track 2: Cellular Immunology
Location: Harbor Room
Speaker

Chair

Howard A. Young

National Cancer Institute, USA

Speaker

Co-Chair

Yongqun Oliver He

University of Michigan Medical School, USA

Session Introduction

John Pixley

University of Nevada, USA

Title: In utero transplantation (IUT) an experimental window into immune self Basic and applied implications

Time : 09:20-09:40

Speaker
Biography:

Pixley trained in internal medicine at Westchester County Medical Center and rheumatology/ immunology at SUNY-at-Stony Brook in New York. He has been on the faculty of the University of Nevada SOM as director of the Rheumatology Division and Chief of Rheumatology at the VA Sierra Health Care System since 1987. His publications include experimental observations on in utero transplantation and clinical observations onextra-articular manifestations of rheumatoid arthritis. He serves on the editorial board of World Journal of Stem Cells and reviews manuscripts for World Journal of Stem Cells, Clinical Rheumatology, Cytotherapy and World Journal of Immunology.

Abstract:

The discovery of common placental circulation between twins coupled with the development of erythrocyte profiling in cattle allowed Ray Owen to determine that dizygotic twins were chimeric with their sibling’s blood cells after birth as a consequence of intermingling of sibling cells via the placental circulation. Thus, he concluded that self-tolerance is acquired during fetal development. Further, he concluded immune tolerance to self is not genetically determined or innate!! Our laboratory has capitalized on these observations to achievelong-term engraftment of allogeneic and xenogeneic stem cells (SC) in sheep and mice following transplantation of SCs during a defined period in fetal development (i.e. IUT). The ease of achieving long-term engraftment and the observed extensive proliferative capacity of transplanted SC confirms Owen’s earlier observations. To further understand this tolerance formation process, we performed parallel experiments testing both engraftment receptivity and immune cell ontogeny during fetal development. These studies identified the thymus as the organ responsible for self-tolerance formation. This process is temporally finite and occurs shortly after the thymus demarcates into cortex and medulla. Studies by Porada transplanting genes in utero and experiments by Rodewald using fetal thymic epithelial progenitors suggest that developmental acquisition of self-tolerance is a consequence of transient fetal thymic epithelial progenitor/cell receptivity, incorporation and expression of circulating antigens during a finite period following thymic demarcation. We term this the antigen exposure model. Implications with regard to IUT’s ability to improve our understanding of immune reactivity vs tolerance and potential in applied therapeutics will be discussed

Speaker
Biography:

Becky M Vonakis is currently Assistant Professor of Medicine at The Johns Hopkins University (JHU) School of Medicine in Baltimore, Maryland. She received her PhD in Biochemistry from the George Washington University and completedpostdoctoral training at NIAMS/NIH and JHU.She is a Fellow of the American Academy of Allergy, Asthma and Immunology. She reviews grants for the National Medical Research Council of Singapore, European COST and the Qatar National Research Fund. She has over30 publications, has been awarded 17 grants/contracts to date (form both the NIH and industry) and mentored more than two dozenstudents and fellows.

Abstract:

Cigarette smoke triggers alterations of both physical and immunological barrier functions of the airway mucosa, leading to inflammatory and pro-neoplastic changes. We used cultures of polarized human PBEC exposed to controlled MCS to characterize a miRNA gene expression signature associated with smoke exposure.PBEC (n=3) isolated from cadaveric lungs of donors (history: negative for respiratory disease, positive for smoking tobacco) were cultured under air-liquid interface conditions and exposed to MCS (undiluted smoke) or filtered air (FA) in a smoke exposure chamber for 16 min (equivalent to two reference cigarettes), cultured for additional 18 hrs, then harvested. MiRNA expression was performed by next generation sequencing with sequencing-by-synthesis technology. Library preparation utilized an Illumina TruSeq small RNA sample preparation protocol. Gene expression was profiled using HT12 v.4.0 Illumina Array platform. MiRNA/Gene expression was assessed in cells harvested 18 hr. after MCS/FA exposure since initial experiments indicated a 42% increase in 7 kD FITC-dextran, a measure of macromolecular permeability, collected from the basolateral supernatant with <20% loss of viability (n=2, WST-1 assay). Twenty-eight miRNAs (as fold change ≥1.2, p<0.05) were regulated by MCS treatment, among which 12 were downregulated. miR1246, a p53-regulated miRNA implicated in cell cycle control, was downregulated8±5-fold. Global gene expression identified MCS-induced increased expression of serpinB4, a gene implicated in neoplastic transformation of airway epithelial cells. The characterization of the miRNA signature and its targets can identify mechanisms of global posttranscriptional gene control with high therapeutic value that can function as disease biomarkers.

Break: Coffee Break 10:30-10:45
Speaker
Biography:

Martha Sklavos received her undergraduate degree from Johns Hopkins University in 2001. She spent the next three years gaining additional research experience as a laboratory technician and subsequently entered the Biomedical Research Graduate Program at the University Of Pittsburgh School Of Medicine in 2004. Martha’s thesis focused on Type 1 Diabetes and she received her PhD in Immunology in 2009. Currently, Martha is a post-doctoral fellow with Leidos Biomedical Research, Inc in the Human Papillomavirus Immunology Laboratory at the Frederick National Laboratory for Cancer Research in Frederick, Maryland. Martha was awarded a “Funding to Advance Research on Cancers in Women” grant from the National Cancer Institute in May 2012 to investigate a novel biomarker for cervical cancer risk. She is now leading several clinical studies to define the role of this novel biomarker in additional cancer types. Martha enjoys conceptualizing ideas and driving projects forward and hopes to fill a similar role in the pharmaceutical industry upon completion of her post-doctoral training.

Abstract:

Background: Differential white blood cell (WBC) counts are routinely used as markers of overall health status as abnormal values can indicate infection, cancer, and other inflammatory diseases.Recently, differences in WBC within normal ranges have been associated with obesity and metabolic syndrome in older populations. However, few studies have evaluated the relationship between WBC levels, obesity and risk of HPV infection and associated disease. Methods: Participants were recruited from the human papillomavirus (HPV) 16/18 vaccine trial in Guanacaste, Costa Rica which enrolled 7,386healthy young women between the ages of 18 and 25.A complete blood count (CBC) was performed as part of a routine clinical assessment at trialenrollment.We performed a cross-sectional study to investigate the associations between circulating leukocyte measures (granulocytes, lymphocytes, monocytes, total WBC), and BMI (underweight (<18.4), normal weight (18.5-25), overweight (25.1-30), obese (>30)), and evaluated the influence of obesity on HPV infection and HPV-associated cervical intraepithelial neoplasia (CIN) lesions in this population. Adjusted logistic regression models were fitted to assess factors associated with (i) leukocyte markers and (ii) HPV infection and associated disease.Adjusted odds ratios (AdjOR) and 95% confidence intervals (95% CI) are presented.Models were adjusted for risk factors typically associated with HPV infection. Results: There was a statistically significant association with higher BMI and higher numbers of granulocytes (AdjORGranulocyte high vs. low tertile: 4.03; 95% CI (3.30, 4.91)), lymphocytes (AdjORLymphycyte high vs. low tertile: 2.87; 95% CI (2.34, 3.51)), monocytes (AdjORMonocytes high vs. low tertile: 2.84; 95% CI (2.22, 3.63)), and WBC (AdjORWBC high vs. low tertile: 4.71; 95% CI (3.87, 5.81)).We observed a decreased association between carcinogenic HPV, but not for non-carcinogenic HPV, for overweight (AdjOR Overweight carcinogenic HPV+ vs.HPV negative: 0.83; 95% CI (0.72, 0.97)) and obese (AdjORObesecarcinogenic HPV+ vs. HPV negative:0.74; 95% CI (0.62, 0.89)) women.Compared to normal weight individuals, obese women had decreased odds of being positive for carcinogenic HPV with low grade CIN (

Break: Coffee Break 10:40-10:55 @ Foyer
Speaker
Biography:

Kay L Medina completed her PhD at the University of Oklahoma Health Sciences Center and post-doctoral training at the University of Chicago as a Fellow of the Irvington Institute for Immunological Research. In 2005, Dr. Medina joined the Department of Immunology at the Mayo Clinic College of Medicine where she is currently an Associate Professor. She has over 60 peer reviewed journal publications and currently serves as Associate Editor for the Journal of Immunology and Frontiers in B Cell Biology. Dr. Medina’s research is focused on the generation and function of B lymphocytes in health and disease.

Abstract:

Common Variable Immunodeficiency (CVID) is a primaryimmunodeficiency disease characterized by low serum immunoglobulin, impaired antibody responses, and recurrent bacterial infections. Furthermore, many CVID patients develop autoimmune disease and malignancies. Together, these immune sequelae suggest that a subset of patients harbor genetic perturbations thatimpact innate and humoral immune function. Dendritic cells (DCs) play an essential role in bridging the innate and adaptive immune responses. Importantly, these cells play an important role in the maturation, differentiation, survival, and immune function ofperipheral B, T, and NK cells. A subset of CVID patients exhibit DC deficiencies and impaired DC functionhas been linked to the pathophysiology of the disease.The Flt3 signaling pathway is critical in DC biology. Therefore, alterations in serum levels of Flt3-ligand and surface expression of the Flt3 receptor on residual DCs were evaluated to determine if defects in the Flt3 signaling pathway represent a novel genetic variable and possible prognostic indicator for impaired immunity in some CVID patients. Variations in serum FL were documented but did not segregate patients with DC deficiencies. However, patients with increased serum FL had increased incidence of autoimmune cytopenias, autoimmune disease, and malignancies, and DCs are known to play a critical role in the detection of neoplastic lesions and maintenance of peripheral tolerance. The identification of underlying genetic causes or contributors to the pathophysiology of CVID is critical for accurate diagnosis and design of treatment strategies, particularly stem cell transplantation. Therefore, identifying defects in the Flt3 signaling pathway as the basis of the DC defect will aid in disease diagnosis and management.

Speaker
Biography:

Igor Malyshev is a Head of the Department of Pathophysiology and Head of the Laboratory of Cell Biotechnology, Medical School at the Moscow State University of Medicine and Dentistry; 2. Head of the Laboratory of Stress, Institute of General Pathology and Pathophysiology, Moscow and 3. Adjunct Professor of Biomedical Sciences, University of North Texas Health Science Center, USA. He is a Member of the board of directors of the International Society for Adaptive Medicine and an Editorial board member of Journal of Biosciences and Medicines. He has published 3 books and monographs and 136 full length articles.

Abstract:

It is accepted that the immune system responds to pathogens with activation of antigen-independent innate and antigen-dependent adaptive immunity. However, many immune events do not fit or are even inconsistent with this notion. The existing model of immune response does not explain how the immunity recovers the homeostasis.We developed a new homeostatic model of the immune response. This model consists of four units: a sensor, a regulator, an effector and a rehabilitator. The sensor, macrophages or lymphocytes, recognize pathogenic cells and generate alarm signals. The regulator, antigen-presenting cells, Тregs and myeloid-derived suppressor cells, evaluate the signals and together with sensor cells program the effector. The effector, programmed macrophages and lymphocytes, eliminate the pathogenic cells. The rehabilitator, M2 macrophages, restrict inflammation, provide angiogenesis and reparation of tissue damage, and restore the homeostasis. We suggest the terms “immune matrix” for a biological template of immune responses to pathogens and “matrix reprogramming” for the interdependent reprogramming of different cells in the matrix. In an adequate immune response, the matrix forms a negative feedback mechanism to support the homeostasis. We defined the cellular and phenotypic composition of a tumor immune matrix(“matrix signature”). A tumor abnormally programs 1) the sensor, macrophages, to a protumor M2 phenotype by secreting anti-inflammatory cytokines, 2) the regulator, Tregs, to the protumorTreg phenotype using chemokines, TGF-β and normal antigens, and 3) the effector, lymphocytes and macrophages, using М2 macrophages and Tregs. Besides, tumor reprogramed M2 macrophages begin performing their “rehabilitation” functions; they attenuate inflammation and activate angiogenesis in the presence of tumor, but not after elimination of it. This “mistake” of M2 macrophages induces protumor programs. Thus tumor reprograms the homeostatic negative feedback mechanism of matrix into a pathogenic positive feedback mechanism. M2 macrophages play a key role in this transformation. Therefore, macrophages are an attractive target for biotechnology. Based on our hypotheses, we are developing a cell biotechnology method for creation of macrophages with a stable antitumor phenotype. We have shown that such macrophages almost doubled the survival time of mice with tumor.

Michal Bajo

The Scripps Research Institute, USA

Title: Role of interleukin-1 system in alcohol drinking and preference

Time : 11:35-11:55

Biography:

Michal Bajo received his PhD in 2002 from Comenius University in Bratislava, Slovakia. He undertook postdoctoral trainingin cellular physiology of addictive disorders using electrophysiological techniques at the Scripps Research Institute (TSRI) in La Jolla, California. Currently, Dr. Bajo is a staff scientist inthe Committee on the Neurobiology of Addictive Disorders at TSRI. His research includes the role of neuroimmune system in development of addiction with focus on alcohol and nicotine.

Abstract:

Behavioral and gene expression studies indicate that the IL-1 system is associated with alcohol drinking behavior.The GABAergic transmission in central nucleus of the amygdala (CeA) is one of the crucial mediators of alcohol addiction. Thus, wehypothesize that the IL-1 system plays an important role in alcohol effectsvia modulation of CeAGABAergicsynapses.We examined interactions betweenIL-1 systemand ethanol on GABAergic transmissionin brain slices containing CeAusing intracellular and whole-cell recordings. Superfusion of IL-1 decreased GABAergic transmission, whereas ethanolenhanced it in B6129SF2/J mice. To elucidate a role of IL-1 receptor antagonist (IL-1ra) in ethanol effects at the CeAGABAergic synapses, we usedIL-1ra knockout (KO) and wildtype (WT) mice.We found differences in baseline phasic and tonic GABA transmission between KOand WT mice.The pretreatment of CeA slices with exogenous IL-1ra (Kineret) reversed changes in the baseline phasic GABA transmission in KO mice. Superfusion of ethanol significantly enhanced GABA in majority of WT mice, whereas in KO only 50% of neurons showed an increase. The pretreatment with Kineret also restored ethanol-induced potentiation of the GABA in KO, while it had no effects in WT mice. Our results suggest that the IL-1 system is involved in a regulation of the CeAGABAergic transmissionand may modulateethanol effects at these synapses. Furthermore, IL-1 system may represent a potential therapeutic target for alcoholism.

Rafael Correa Rocha

Institute of Health Research Gregorio Marañón, Spain

Title: Immune mechanisms implicated in the tolerance induction to food allergens in children

Time : 11:55-12:15

Speaker
Biography:

Rafael Correa Rocha has completed his first PhD in Biology at the Universidad Complutense of Madrid (Spain) in 2004. His thesis was awarded with the National Prize of Doctorate 2005. He joined the ISREC (Epalinges, Switzerland) as a post-doctoral researcher and afterwards, he obtained a position as Assistant Professor at the HopitauxUniversitaires de Genève (Switzerland). He joined the IISGM of Madridas a Senior Scientist in February 2008. He completed a second PhD in Medicine at the Universidad Autónoma of Madrid in 2014. At present, he is the Head of the Laboratory of Immune-regulation at IISGM. He has published more than 40 papers in reputed journals.

Abstract:

Food allergy affects about 6% of young children and 3–4% of adults in westernized countries. Food allergy is the most frequent reason for anaphylactic reactions in children, and its prevalence and persistence is undergoing an important increase in the last years. Although the origin of the allergic process is clearly an altered response of immune system, there is still a limited knowledge about the immune mechanisms implicated in allergy and tolerance acquisition. We have investigated the immune changes associated to the desensitization to food allergensin allergic children treated with oral immunotherapy. Our recent findings[1,2]demonstrated that, tolerance achievement is associated with the recovery of a new CD4 T-cell subset with a hypo-proliferative phenotype and a marked increase in the regulatory T-cell (Treg) population. The Treg increase was related with the control of effector immune responses and the disappearance of allergy-related symptoms. These results contribute to better understanding of immune responses in allergic patients, and could provide the basis for the use of these immune subsets as predictive and diagnostic markers of clinical outcome, and as a tool to follow the efficacy of immunotherapy easily measurable in peripheral blood.

Biography:

M. Lipinska-Gediga has completed her PhD in application of PCT monitoring sepsis/septic shock patients in ICU from Medical University in Wroclaw,PL on 1999. She is a specialist of anesthesiology and intensive therapy, and assistant professor in Chair and Department of Anesthesiology and Intensive Therapy of University Hospital in Wroclaw. She has published on the topic of her professional interest in reputed journals.

Abstract:

Sepsis is not a single disease, but highly heterogeneous syndrome that is the net result of host and pathogen interactions. Severe sepsis/septic shock are advanced clinical conditions representing patient’s response to infection and having high mortality rate. Early evaluation of sepsis stage is one of key survival factors.PCT (procalcitonin) a prohormone of calcitonin originates from calcitonin-I-(CALC-I) gene on chromosome 11and in septic conditions different organs and cell types are source of PCT. Procalcitonin represents the innate part of host response to microbial infection.Microvascular dysregulation with hyporesponsive vessels and heterogeneous blood flow are important symptoms of sepsis. The vascular endotheliumhas been shown to play a pivotal role in pathophysiology of sepsis as a potent modulator of immune-inflammatory host response. Endocan (EMS-1) a 50kDa dermatan-sulphate-proteoglycan is expressed by endothelial cellsand can be detected at low levels in the serum of healthy individuals. Inseptic patients endocan blood levels are likely to be associated with endothelial injury and are reported to be related to severity of illness and outcome. I would like to present the preliminary results of just started prospective observational study of endocan predictive and diagnostic value compared with PCT, APACHE II, SOFA, in septic (study group) and noninfectious patients (control group).

Speaker
Biography:

Chunxia Su has completed his PhD at the age of 30 years from Nanjing Agriculture University.She has published more than 10 papers in reputed journals

Abstract:

IL-2 is one of the most extensively used adjuvants for vaccination to stimulate the proliferation and differentiation of effector T cells.Follicular helper T cells (Tfh cells)are a new CD4+T cell subset that specializes in helpingformation of germinal center (GC) and, consequently, mediated the T-dependent humoral immunity response. However, it is uncertain whetherIL-2 as an adjuvant may modulate the Tfh cells immune response. In this study, we investigated the effects of IL-2 adjuvant for adenovirus-vectored FMD vaccine on production of FMDV VP1 specific IgG,IgG1 and IgG2a, secretion of IFN-γ,IL-4 and IL-21 in serum, expression of Bcl-6 mRNA from mice after immunization. Further, we explored the generation of Tfh cells, GC B cells and formation of GC from mice after immunization. The data showed that IL-2 as an adjuvant for adenovirus-vectored FMD vaccineenhanced both levels of antibodies and secretion of IFN-γ,IL-4 and IL-21 in serum, which revealed the potent adjuvant activity of IL-2 could enhance the generation of Th1(IFN-γ) and Th2(IL-4), as well as Tfh(IL-21) cells. The further effects of IL-2 on Tfh cells were detected and showedthat IL-2 as an adjuvant for adenovirus-vectored FMD vaccine increased the generation of Tfh cells and the expression of Bcl-6 mRNA, additionally, IL-2 as an adjuvant for adenovirus-vectored FMD vaccine substantially increasedthe generation of GC B cells and formation of GCs, which revealed that IL-2 as an adjuvant for vaccination induced generation of Tfh cells and then mediated T-dependent humoral immunity response.

Break: Lunch Break 12:55-13:40 @ Eden’s Landing Restaurent
Speaker
Biography:

Gerlies Treiber received her MD form Medical University Graz in 2002 and completed a postdoctoral research fellowship in Dr. Robert Rizza lab at Mayo Clinic, Rochester, MN, US. Dr. Treiber is an active hospital clinician and assistant professor at the Division of Endocrinology and Metabolism of Medical University Graz, Austria. In the past years she has been studying the role of Vitamin D in immunomodulation of regulatory T cells in humans and diabetes type 1. She has presented in national/international meetings and published several articles in peer-reviewed journals.

Abstract:

Vitamin D receptors are found on several cells of the innate and adaptive immune system and the impact of vitamin D deficiency in the pathogenesis of immunomediated diseases such as diabetes type 1, multiple sclerosis and inflammatory bowel diseases have been highlighted. Animal and in vitro studies suggest that vitamin D is involved in reducing the risk of autoimmunity by modulating regulatory T cells, which are pivotal to maintain self-tolerance. We have previously shown that cholecalciferol (vitamin D3-a precursor of the active metabolite) is able to increase frequency of peripheral regulatory T cells in the blood without negatively effecting suppressive capacity and apoptosis in healthy humans and in vitro exposure to cholecalciferol as well leads to increased percentage of regulatory T cells. We hypothesize that cholecalciferol may increase regulatory T cells in the intestinal mucosa, which harbors a large number of immune cells in the gut-associated lymphoid tissue. In a systematic assessment we determined the distribution of CD4+, CD8+ and Foxp3+regulatory T cells in several regions of the upper and lower gastrointestinal tract. Our data show a significant variation in the baseline T cell landscape along the human gastrointestinal tract and an immunomodulatory effect of cholecalciferol on T cells subpopulations in the intestinal mucosa of humans. These studies support the role of vitamin D as an immunomodulatory adjunct in the therapy of immunomediated diseases.

Biography:

Dr. Janeen Salak-Johnson joined the Department of Animal Sciences at the University of Illinois at Urbana-Champaign in November of 1999. Dr. Salak-Johnson hails from Pittsburg, Pennsylvania and is considered a transplant resident of Texas as well as a prominent alumna of The Texas Tech University where she garnered her status as a Ph.D. graduate. Her background focuses primarily within the fields of Animal Sciences, Neuroscience and Immunological Sciences which she currently uses to assess the welfare of production swine in various housing milieus and their environment. One of the reasons Dr. Salak-Johnson is highly interested in animal welfare and behavior is because of her knowledge of the many different variables that can affect the health of an animal. She is now in the process of integrating applied sciences into a field of Animal Sciences that uses Observational Studies to assess what needs to be done in order to improve the welfare of housed production animals of which her extensive background in neuroscience and immunology has enabled her to properly assess and implement many changes in the field of Agriculture

Abstract:

Host immune response and other factors that compromise health are important in the pathogenesis and outcomes of infectious disease. Often, findings reported from studies investigating the effects of stress on the immune system are conflicting and difficult to interpret. These discrepancies may partly be explained by types and durations of the stressors, age and physiological status, and the aspect of the immune system being measured—to name a few. We have begun to unravel other biological factors that may affect immune- and stress responsiveness as well as the maternal effects on her progeny. We found that day of gestation is an important biological factor that can impact immune and endocrine statuses more-so than the stressor alone. Our data also indicate that feeding dietary modulators—high fiber or the probiotic S. boulardii—to pregnant pigs, impacts the immune and endocrine statuses of the female and can influence immune status and stress responsiveness of her progeny. Feeding pregnant pigs a high-fiber diet, differentially affects her immune status, resulting in a skewed adaptive immune profile, which may ultimately affect the growth and immune status of her progeny. Feeding pregnant pigs, probiotics may modulate the stress-responsiveness and immune status of the female and progeny during birthing and weaning processes. Taken together, these data imply that the physiological status of the female can impact immune and endocrine status and the stress response and immune status of the dam and her progeny can be changed with the inclusion of dietary supplementation.

Mary L S Queiroz

State University of Campinas, Brazil

Title: Immunohematopoietic modulation by the alga chlorella in obese mice

Time : 14:20-14:40

Speaker
Biography:

Mary Queiroz has completed her PhDfrom the University of Manchester, England, and her postdoctoral studies from WEHI, Melbourne, Australia. Full professor, director of the Laboratory of Immunopharmacology, Medical Faculty, UNICAMP, Campinas, Brasil. She has published more than 80 papers in reputed journals and presented several pioneer and original results in the literature, starting with the focus of her studies on the modulation by medicinal plants ofimmunohematopoietic regulatory mechanisms, aiming to increase or restore the host's own defenses which can inhibit infectious and malignant processes.

Abstract:

Purpose –Investigation of modulating effects of Chlorella on the medullar and extramedullar hematopoiesis and cytokine production of obese mice. Methods – Interaction between stromal cells and hematopoietic progenitor cells by long-term bone marrow culture. Growth and differentiation of bone marrow and spleen progenitors (CFU-GM) by clonal culture.Cytokines by ELISA. Results – In obese mice we observed reduced capacity of stromal cell layer to support CFU-GM, decreased numbers of total non-adherent stromal cells, increased levels of IL-1, IL-6, TNF-alfa, TGF-beta, reduced levels of IL-10, and extramedular hematopoiesis. This latter finding is pioneer in the literature and might be related to the accumulation of macrophage in adipose tissue,a common feature in human and experimental obesity, which is considered responsible for the majority of complications observed in this disease. CV treatment restored all these changes to normal values. Conclusion - Additional findings, already published (Vecina et al, 95, 45-52,2013), were also pioneer in literature showing that prevention by CV of high-fat diet-induced insulin resistance in obese mice is due to improvement in insulin signaling pathway by increasing phosphorylation levels of IR, IRS-1 and Akt and reducing phosphorylation levels of IRS-1ser307 . We also found that CV prevents high-fat diet-induced dyslipidemia by reducing triglyceride, cholesterol and free fatty acid levels. Altogether our findings suggest that prevention by CV of the deleterious effects induced by high-fat diet is a good indicator for its use as a prophylactic agent against obesity-related complications.

Baochi Liu

Shanghai Public Health Clinical Center Affiliated to Fudan University, China

Title: CCR4 play a key role in a mouse fracture healing model

Time : 14:40-15:00

Speaker
Biography:

Baochi Liu received his Ph.D. from Zhengzhou University in 2007. He received his B.S.in 1983. He has many Peer-reviewed Publications in reputed journals. His research interest includes general surgery, surgery infection and trauma. He is currently working as a Director and Professor in Department of Surgery, Shanghai Publical Health Clinical Center Affiliated to Fudan University, Shanghai, China.

Abstract:

Objective: Fractures can trigger an immune response that disturbs the homeostasis of osteoblast and osteoclast through the production and release of cytokines and their receptors. The purpose of our study was to investigate CCR4 as potential cellular components of the osteoimmune system's response to an in vivo model of bone injury. The absence of CCR4 influences the fate of other responder cells in proliferation, differentiation, matrix production, and ultimate callus formation. Methods: Tibia fractures were induced in 50 CCR4-deficient mice and 50 control C57BL/6 mice. Examinations of radiographs, basic histology, mechanical testing, flow cytometry, immunohistochemical, as well as enzyme-linked immunosorbent assay for the effector cytokines interleukin-2 (IL-2), interferon, and IL-6 were performed. Results: Animals deficient in CCR4 cells revealed less mature histologic elements and quantitative decreases in the expression of major bone (bone sialoprotein) and cartilage (type II collagen) matrix proteins and in the expression of bone morphogenetic protein 2 at a critical reparative phase. Moreover, only CCR4-deficient animals had an increase in the osteoprogenitor antiproliferative cytokines IL-6 and interferon at the reparative phase. The result was improved stability at the repair site and an overall superior biomechanical strength in CCR4-deficient mice compared with controls. Conclusion: The evidence for a role of CCR4 in the context of skeletal injury indicated the importance of the immune system's influence on bone biology, which is associated with the field of osteoimmunology, and offers a potential molecular platform from which to develop essential therapeutic strategies.

Petr Kolenko

Institute of Macromolecular Chemistry, Czech Republic

Title: New protein constructs from KLRB1 superfamily for immunologic and structural research

Time : 15:00:15:20

Speaker
Biography:

Petr Kolenko has completed his Ph.D at the age of 27 years at the Czech Technical University. He spent more than two years as a post-doc at the Institute of Biochemistry and Biotechnology, MLU, Halle, Germany. He spent half a year in Birmingham (Aston University), UK, as a second postdoctoral stage. He has published 14 papers in reputed journals.

Abstract:

Natural Killer (NK) cells represent a component of innate immunity. These large granular lymphocytes play an important role in defense against viruses, parasites, tumors, etc. Many molecular mechanisms that participate in their activity have been revealed. Vast majority of structure-function studies of C-type lectin-like (CTL) NK cell receptors have used recombinant extracellular domains produced in E. coli after successful refolding. Minority of the proteins have been produced in eukaryotic expression systems that are able to perform post-translational modifications. Current studies of CTL receptors (e.g. members of the Ly49 class) have shown that extension of constructs usually limited to compact CTL domain may lead to novel structural observations and new mechanisms of binding of the receptors. Our previous research of KLRB1 superfamily was also limited to analysis of short domain-only proteins produced in E. coli. We have currently produced several variants of receptors from KLRB1 superfamily that differ in chain length and amino acid sequence in various protein expression systems. Our aim is step-by-step development and testing of methods for production of complete NK cell receptors for thorough analysis using wide scale of characterization measurements including structure-function studies. The project is supported by BIOCEV CZ.1.05/1.1.00/02.0109 ERDF, and MSMT projects EE2.3.30.0029, LG14009.

Speaker
Biography:

Ahmed Mohammed Ashshi has completed his PhD(1999) Doctor of Philosophy in Medical and Molecular Virology,Faculty of Medicine, University of Manchester, United Kingdom(UK). AIBMS:(2001) Professional qualification in Medical Laboratory Sciences, Associate, Institute of Biomedical Sciences, United Kingdom (UK). Dean, Faculty of Applied Medical Sciences, Umm Al Qura University, Makkah Asociate Professor of Medical and Molocular Virology, Faculty of Applied Medical Sciences, Umm Al Qura University, Makkah, Kingdom of Saudi Arabia Chairman, Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al Qura University, Makkah, Kingdom of Saudi Arabia.

Abstract:

Background: Activins and follistatin are involved in the regulation of immune system and their importance in liver diseases has recently emerged Objectives:To measure the effect(s) of chronic hepatitis C (CHC) genotype 1 and 4 on the serum concentrations of activin-A, activin-B and follistatin, and to determine their correlations with viral load, liver damage, interleukin-6 (IL-6) and tumour necrosis factor (TNF)-α. Methods: Serum samples were collected from 20 male and 20 female treatment naïve CHC genotype 1 and 4 Saudi patients (10 males and 10 females for each genotype), to measure activin-A, activin-B and follistatin by ELISA and the results were compared with 40 gender and age matched healthy participants. Additionally, the serum levels of the candidate proteins were correlated with IL-6, TNF-α, viral load and AST platelet ratio index (APRI). Results: SerumIL-6, TNF-α,activin-A and activin-B were significantly increased, whereas serum follistatin was significantly decreased, in both genders of CHC patients compared to control subjects.In both viral genotypes, activin-A was strongly and positively correlated with the viral load, APRI, IL-6 and TNF-α, and negatively with albumin (P < 0.01). Activin-B showed similar correlations to activin-A but only in CHC genotype 1 patients and it was weaker than activin-A. No correlation was detected for follistatin. Conclusion: CHC genotype 1 and 4 significantly altered serum activinsand follistatin, and the dysregulation of activins/follistatin axis could be associated with host immune response, viral replication and liver injury. More studies are required to elucidate the role(s) and clinical value of activins and follistatin in CHC.

Biography:

I graduated in Biomedical Sciences from Thammasat University, Thailand on 2008 and completed a postdoctoral research fellowship at Immunopathology, SA Pathology,Women's and Children's Hospital, University of Adelaide, Australia on 2013. I have been Deputy Dean for research and graduate Faculty of Allied Health Sciences, Naresuan University Phitsanulok, Thailand. I am currently Assistant Professor in Immunology at Naresuan University of Thailand. My present research activities are in the field of immunology and inflammation. My research team is focusing on the macrophage.

Abstract:

Moringa oleifera Lam. (MO) has been reported to harbor anti-oxidation and anti-inflammatory activity and useful in the treatment of inflammatory diseases. However, despite these findings there has been little work done on the effects of MO on immune cellular function. Since macrophages, TNF and related cytokines play an important pathophysiologic role in lung damage induced by cigarette smoke, we examined the effects of MO on cigarette smoke extract (CSE) – induced cytokine production by human macrophages. An ethyl acetate fraction of MO (MOEF) was prepared from fresh leaves extract of Moringa and shown to consist of high levels of phenolic and antioxidant activities. Human monocyte derived macrophages (MDM) pre-treated with varying concentrations of MOEF showed decreased production of TNF, IL-6 and IL-8 in response to both LPS and CSE. The decrease was evident at both cytokine protein and mRNA levels. Furthermore the extract inhibited the expression of RelA, a gene implicated in the NF-κB p65 signaling in inflammation. The findings highlight the ability of MOEF to inhibit cytokines (IL-8) which promote the infiltration of neutrophils into the lungs and others (TNF, IL-6) which mediate tissue disease and damage.

Break: Coffee Break 16:00-16:15 @ Foyer
Speaker
Biography:

Zhou received Ph.D degree (2004) in Xiangya School of Medicine, Central South University, China. She did her postdoctoral training in University of Pittsburgh and H.Lee Moffitt Cancer Center in USA till 2009. She is professor in Zhongshan School of Medicine, Sun Yat-sen University since 2010. Her research focuses on the mechanisms regulating immune cell differentiation (including B cell and myeloid cells), as well as their significance in immune related disorders. She have published 20 papers in peer-reviewed journals.

Abstract:

Cyclooxygenases (COXs) and their prostanoid products play important roles in a diverse range of physiological processes, including in the immune system. Here, we provide evidence that COX-1 is an essential regulator in early stages of B cell development. COX-1-deficient mice displayed systematic reduction in total B cells, which was attributed to the arrest of early B cell development from pro-B to pre-B stage. We further demonstrated that this defect was mediated through down-regulation of the Janus kinase/signal transducer and activator of transcription 5 (JAK/STAT5) signaling and its target genes, including Pax5, in COX-1-/- mice. Mechanistic studies revealed that COX-1 derived thromboxane A2 (TxA2) could regulate JAK3/STAT5 signaling through cAMP-PKA pathway, via binding with its receptor-TP. Administration of TP agonist could be able to rescue the defective B cell development and JAK/STAT5 signaling activity in COX-1-deficient mice. Moreover, administration of low-dose aspirin caused a significant reduction in total B cells in peripheral blood of healthy human volunteers, coincidentally with reduced TxA2 production and downregulation of JAK/STAT5 signaling. Taken together, our results demonstrate that COX-1 derived TxA2 plays a critical role in the stage transition of early B cell development through regulation of JAK/STAT5 signaling, and indicate potential immune-suppressive effect of low-dose aspirin in humans.

Speaker
Biography:

Galina Reva is an Associate Professor in Far Eastern Federal University, Russia

Abstract:

Introduction: The main researches of toxicokinetic and nanoparticles focus on studies related to the assessment of biological and toxic effects of nanoparticles, as well as possible future use as a means of drug delivery and diagnostic purposes. Study the most general laws of the biological and toxic effects of nanoparticles, depending on their shape, size, form factor, the source material, surface area, surface charge, impurities and other physical and chemical characteristics of the structure and the mechanisms of their effects on cells and tissues, consider topical issues nanotoxicology. Equally important are the studies that determine the dose, route of delivering and the concentration of nanoparticles in the target organ, duration of exposure [5, 8]. The purpose of this study was to investigate the reactions of the structure of the mucosa of the gastrointestinal tract in CBA mice at inserting of oral multi-walled carbon nanotubes, and also consider the features of overcoming the epithelial barrier, intestinal absorption and renal responses. Methods: During the study the different parts of the gastrointestinal tract and kidneys 60 CBA mice (vivarium TIBOH FEB RAS) after oral inserting of nanotubes for 1, 2, 3, 4, 5, 6 days. To eliminate the effect on the proliferative activity of epithelial cells of the mucous membrane of the gastrointestinal tract of estrogen in the experiments involved only male mice. Biopsy specimens were carried out in accordance with the "Rules of the work with experimental animals" from 12/08/77. Gastric biopsies were taken in accordance with the gold standard of WHO cardia, fundus and antrum. The collected material was sliced to semithin tissue sections of gastrointestinal tract and kidneys, which were stained with hematoxylin-eosin. Analysis of the material held on the microscope Olympus Bx51 (Japan) with a digital camera, CD 25, and proprietary software for morphometric studies. Results: During the experiment, there was a migration of nanotubes through mucosal barrier, the epithelium and its basement membrane. Nanotubes on the first day of the experiment are identified at the level of mucosal mucosal barrier wall of the esophagus, cardiac, fundal and antral. On the second and third days in the wall of the mucosa of the duodenum, small intestine and colon nanoparticles overcome mucosal, epithelial barrier, where they are identifiable by light microscope. The second face of nanotubes passing through the stage of the epithelial barrier is directly cytoplasm of the epithelium. Discussion: First nanotubes occupy border position in the apical part of the epithelium, then they reach the basement membrane of the epithelium, where they are arranged in a line parallel to the basal membrane. In case of oral insertion of nanotubes reaction and permeability of the epithelium of the mucous membrane of the intestine is most pronounced compared to epithelial cells of the mucous membrane of the stomach, duodenum, small intestine and colon. According to our data, the morphological picture of the distribution of nanotubes in the epithelium is similar to that in the microbial contamination of Helicobacter pylory of mucosa shells of the gastrointestinal tract. In the absence of receptor recognition of nanotubes due to the presence of certain chemical properties, as part of a short-term experiment, there is only contamination of nanoparticles in epithelial cells. In this case, we have noted as a defensive reaction of the mucous membrane increased secretory activity of the glandular epithelium. In general, we observed that the multi-walled carbon nanotubes do not have a pronounced toxic effect on the body CBA mice with short-term experiment. Despite this, it is necessary to point out some of the nanomaterial immunogenicity and increased migratory activity of the cells, which is manifested in the lymphoid infiltration.

Aslihan Turhan

Massachusetts Eye and Ear Infirmary, USA

Title: In search for mediators of dendritic cell recruitment to the cornea during inflammation

Time : 16:55-17:15

Biography:

Aslihan Turhan is a PhD in Immunology. Worked as an Instructor at Harvard Medical School in Surgery department and in Ophthalmology department. Dr. Turhan is currently serving as an assistant professor in Gaziantep University, Medical School, Turkiye. During her studies in MSSM and in HMS she designed live imaging techniques for intravital imaging of cremaster muscle, colonic mucosa and cornea. She is an expert in cell trafficking, inflammation and imaging. Dr. Turhan is experienced in target identification for drug development, in inflammatory conditions and intravascular cellular interactions. Her primary interests are cell-cell interactions in response to inflammation, target identification for drug development for manipulating cell trafficking. She has identified targets for cellular interactions in sickle cell disease and DC trafficking in cornea in response to inflammation. Her work on sickle cell disease is currently in clinical trial. Dr. Turhan has published in peer-reviewed journals, is in editorial board of Journal of Infectious Diseases and Therapy. She has patent applications for treatment approaches in sickle cell disease and corneal inflammation.

Abstract:

Purpose:
Dendritic cells play an important role in the immune response in cornea in inflammation as well as in graft rejection. It has been previously shown by other groups that there is a clear correlation between corneal vascularization and graft rejection. Corneal vasculature mediates the recruitment of leukocytes to corneal surface by interactions between adhesion molecules on leukocytes and on endothelial cell on vascular beds. We have previously shown the recruitment of Cs to the cornea is partially mediated by vascular cell adhesion molecules (VCAM)-1 and P-selectin. In this study we showed the contribution of MAdCAM-1, a molecule previously not described on the ocular surface, is another molecular target mediating DC homing to cornea.
Methods:
We studied the rolling and adhesion behaviour of fluorescently-labeled DCs, adoptively transferred to BALB/c mice by intravital microscopy (IVM, 500 Mikron Instruments) in steady state and in inflammation in vivo. To study the contribution of MADCAM to the recruitment behaviour of DCs in corneal vasculature, anti-MAdCAM-1 blocking antibody or controls antibody were injected intravenously (i.v.) 30 minutes before IVM recordings. Homing (recruitment) of DC to normal or inflamed corneas were studied by ex vivo. Also, 24 hours after i.v. injection of fluorescently-labeled DC, recruitment were studied by confocal microscopy (Olympus Fluoview 1000) of the corneas.
Results:
While VCAM-1 and P-selectin contributed partially to the recruitment of DCs to the corneal vasculature, MAdCAM-1 is found to be an important candidate target regulating recruitment to the corneal surface. MAdCAM-1 significantly reduced the rolling fraction (4.1 % vs controls (20.7%; p< 0.001)) and the sticking of DCs (0.4% vs (3.4%; p< 0.001) in inflamed corneas as compared to controls. This effect of MAdCAM on DC recruitment was further supported by the blockade of anti-MAdCAM-1 (18.4 cells/mm2; p=0.005) or its ligand α4β7 (4.5 cells/mm2; p=0.003), α4 (12.1 cells/mm2, p=0.032) and β7 (3.2 cells/mm2, p=0.007), treatment showing significant reduction of DC homing to the inflamed cornea as compared to controls (51.5 cells/mm2). This effect was supported by studying α4β7 and L-selectin expression on CD11c-high DC population by flow cytometry.
Conclusions:
Our study demonstrated, for the first time that MAdCAM-1 played a role in leukocyte recruitment to the cornea through limbal vessels in inflamed corneas. MAdCAM 1 might be a good candidate as a new molecular target for pharmacological intervention for conducting leucocyte recruitment in response to inflammation in cornea.
Support: NIH K08-EY020575, Fight for Sight, Falk Medical Research Trust, Research to Prevent Blindness Career Development Award

Speaker
Biography:

Sandra Ayuk (AIMLT, Medical Laboratory Technology, UCTH, Calabar, Nigeria,B.TechHons, M.Tech, Biomedical Technology, University of Johannesburg, South Africa) is currently pursuing a Doctorate degree in Biomedical Technology, Laser Research Centre (LRC), University of Johannesburg. She is specialized in haematology and blood transfusion as well as laser interaction in wound healing focusing on diabetic wound healing. She has presented in several conferences both locally and internationally, and has published some of her works in peer-reviewed journals. She has recently received three merit awards from her research output and was also nominated the president of the African Laser Congress (ALC) student association. She is also a member of World Association of Laser Therapy (WALT) and Cameroon Medical Laboratory Society (CAMELS).

Abstract:

Background: Low Intensity Laser Irradiation (LILI) is a non-invasive form of therapy that uses lasers of low energy. On application of these lasers to tissues, photochemical, biological and physical responses are stimulated in photoreceptor molecules within the cell.It produces cytokines and heat shock proteins which regulate the body’s immune response locally and consistently. Studies have shown that the immune system is affected in people with ‘slow to heal’ wounds.This study aimed to evaluate various genes involved in the ECM and the role of LILI diabetic wounded fibroblast cells.
Method: Normal (unstressed) and diabetic wounded (stressed) models of isolated human skin fibroblasts were used. The cells were incubated for 48 h after irradiation using a diode laser at a wavelength of 830 nm at a fluence of 5 J/cm2. Non-irradiated (0 J/cm2) normal and diabetic wounded cells served as controls. To determine the expression of 84 genes, real-time reverse transcription (RT) quantitative polymerase chain reaction (qPCR) was used in a PCR array. Results: LILI mediated the expression of genes in the ECM and its adhesion molecules. Appropriate controls were used for gene profiling and showed significant increase and decrease in expression 48 h post-incubation.Sixty one genes were significantly regulated (55 up-regulated and 6 down-regulated) in normal cells; 42 genes were regulated (9 up-regulated and 33 down-regulated) in diabetic wounded cells. Several genes were seen to be down-regulated in diabetic wounded cells as compared to normal.
Conclusion: LILI stimulates gene expression of proteins involved in the ECM in vitro at 830 nm with a fluence of 5 J/cm2 which may turn to trigger immune-response. A detailed understanding of the molecular aspects may create a breakthrough for LILI as an alternative treatment for difficult to heal wounds.

Gaoyun Yang

Beijing Friendship Hospital of Capital Medical University, China

Title: The study of chemokine-like factor 1 (CKLF1) antagonist peptides C19 in mouse model with atopic dermatitis

Time : 17:35-17:55

Biography:

15 years of clinical work experience in dermatology department: • 10 years of skin diseases research experience in R & D department of Johnson & Johnson, DuPont Pharmaceuticals and Peking Union Medical College • Published more than 50 research or clinical study papers MEMBERSHIP OF PROFESSIONAL SOCIETY 1. Foundation Fellow of the Asian Academy of Dermatology and Venereology 2. Board Member of Psoriasis Group of Chinese Society of Dermatology 3. Editor of the “Journal of Practical Dermatology”, “Chinese Journal of Dermatovenereology” 4. Member of AAD, SID, AAI, SAPA, CBA

Abstract:

Objective:
To explore the function of chemokine-like factor 1 (CKLF1) antagonist peptides C19 in the mouse model with atopic dermatitis.
Methods:
①The mouse model of atopic dermatitis were established by sensitization with ovalbumin (OVA) through the skin.60 BALB/c mice were randomly divided into atopic dermatitis (AD) group, control group, prevention, and treatment group, 15 mice in each group. The atopic dermatitis group and control group BALB/c mice were sensitized with OVA (100μg) or saline applied in 100μl to a sterile patch. The patch was placed for a 1-week period and then removed. Two weeks later, an identical patch was reapplied to the same skin site. Each mouse had a total of three 1 week exposures to patch separated from each other by 2 week intervals. Prevention group 1 day prior to the weekly sensitization and interval of 2 weeks in the middle of the stage was local subcutaneous injection with CKLF1 antagonist peptides C19 5μg in 20μl each time. The sensitization process of treatment group was the same as dermatitis groups, and 24h after the sensitization treated with CKLF1 antagonist peptides C19 10μg in 20μl local subcutaneous injection in mice skin, once every five days, a total of 2 times.②To detect the gene expression profile of microRNA in total RNA of every groups by ULS™ fluorescence detection calibration.
Results:
The AD group showed local inflammation in the skin compared with the control group and prevention group, epidermal thickening and significant inflammatory cellular infiltration were observed and the lesion of treatment group mice improved after 2 times treatment with C19. ② To detect the gene expression profile of microRNA in total RNA of every groups by ULS™fluorescence detection calibration, the data indicate that the expression level of microRNA which regulate the gene of inflammatory cytokines in the lesions was up-regulated in CKLF1 antagonist peptides C19 treatment group and prevent group.
Conclusions:
The expression levels of microRNA which may be involved in regulate the specific gene of inflammatory cytokines in the lesions was down-regulated in mouse model of the atopic dermatitis group, and after topical treatment and prevention, the specific gene of inflammatory cytokines in the lesions was up-regulated, which suggested that prevention and treatment with the CKLF1 antagonist peptides C19 maybe played an important role in atopic dermatitis, and contribute to the further understanding and exploring new anti-inflammatory polypeptide for the treatment of atopic dermatitis.

Break: Panel Discussion 18:15-18:35
Billie Holiday
  • Track 7: Infectious Diseases and Immune System
    Track 8: Auto Immunity
Location: Billie Holiday
Speaker

Chair

Kaihong Su

University of Nebraska Medical Center, USA

Session Introduction

Meg Mangin

Executive Director
Chronic Illness recovery, USA

Title: Clinical evidence of immune system dysregulation caused by intracellular infection

Time : 09:20-09:40

Speaker
Biography:

Meg Mangin, R.N. is a registered nurse licensed in the state of Wisconsin. She attended St. Mary’s School of Nursing in Rochester, MN and graduated from Milwaukee County General School of Nursing. She held staff nurse positions in coronary/intensive care, and provided skilled home-nursing services in a variety of medical specialties. Meg headed the Wisconsin La Leche League for five years and served on a National Institutes of Health (NIH) State of the Science panel. She also served 6 years on an NIH Data, Safety and Monitoring Board. Meg was one of the earliest adopters of Inflammation Therapy and participated in its early research. She led a team of online nurses in counseling hundreds of patients on their road to recovery and was a presenter at Days of Molecular Medicine in Karolinska, Sweden, the Understanding Aging Conference in Los Angeles and the International Conference on Autoimmunity in Porto, Portugal. She is the author of Observations of Jarisch-Herxheimer Reaction in Sarcoidosis Patients and a co-author of a chapter in the 2006 medical textbook titled Vitamin D: New Research, published by Nova.

Abstract:

Intracellular bacteria may cause immune system dysregulation via actions on the vitamin D receptor (VDR), the nuclear receptor which regulates the innate immune system. Cell wall deficient (CWD) bacteria persist within cellular cytoplasm (including phagocytes), by using strategies to evade elimination. One of those strategies appears to be downregulation of the VDR. This is evidenced by elevated 1,25-dihydroxyvitamin D (calcitriol), in the absence of hypercalcemia. High levels of calcitriol suggest that bacterial ligands are able to antagonize or otherwise inhibit VDR function and prevent the receptor from expressing enzymes necessary to keep calcitriol in a normal range. Calcitriol activates the immune system by binding to the VDR to genomically induce transcription of antimicrobial peptides (AMPs) which eliminate pathogens. Normally, renal production of calcitriol is tightly self-regulated, with the end product down-regulating its own further production. Production of calcitriol in extra-renal cells is controlled by cytokines, lipopolysaccharide,nitric oxide and intracellular vitamin D binding protein; when extra-renal tissues are parasitized by CWD bacteria, excess calcitriol production is stimulated and renal control of calcitriol production is lost.Elevated calcitriol indicates the immune system recognizes the presence of parasitic bacteria and is attempting to combat them by increasing the production of calcitriol in order to transcribe AMPs. The result is chronic low-grade inflammation, persistent intracellular infection, and eventual multi-morbidity. Administration of the angiotensin blocker olmesartan medoxomil demonstrates reversal of immune system dysregulation. When used at higher than the standard antihypertensive dose,olmesartan appears to be anagonistic VDR ligand which upregulates the bacterially-inhibited VDR. This is evidenced by a significant reduction in elevated calcitriol. In addition, an apparent increase in AMP transcription, and thus elimination of intracellular bacteria, is evidenced by symptoms of Jarisch-Herxheimer reaction and eventual reduction in inflammatory symptoms. In conclusion, intracellular infection compromises VDR activity and inhibits the innate immune system. Olmesartan, which enhances VDR expression and eliminates the offending bacteria, represents a clinical breakthrough in the treatment of immune system dysregulation.

Biography:

Yehuda Shoenfeld is the founder and head of the Zabludowicz Center for Autoimmune Diseases, at the Sheba Medical Center which is affiliated to the Sackler Faculty of Medicine in Tel-Aviv University, in Israel. Dr. Shoenfeld is the Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases at the Tel-Aviv University. His clinical and scientific works focus on autoimmune and rheumatic diseases, and he has published more than 1700 papers in journals such as New Eng J Med, Nature, Lancet, Proc Nat Acad Scie, J Clin Invest, J Immunol, Blood, FASEB, J Exp Med, Circulation, Cancer and others. His articles have had over 31,000 citations. He has written more than three hundred and fifty chapters in books, and has authored and edited 25 books, some of which became cornerstones in science and clinical practice, such as "The Mosaic of Autoimmunity", "Infections and Autoimmunity" and the textbook "Autoantibodies" and "Diagnostic criteria of autoimmune diseases", all of which were published by Elsevier and sold by the thousands. He is on the editorial board of 43 journals in the field of rheumatology and autoimmunity and is the founder and the editor of the IMAJ (Israel Medical Association Journal) the representative journal of science and medicine in the English language in Israel, and also is the founder and Editor of the "Autoimmunity Reviews" (Elsevier) (Impact factor 6.6) and Co-Editor of "Journal of Autoimmunity" (Impact factor 7.4). For the last twenty years Dr. Shoenfeld has been the Editor of "Harefuah" The Israel journal in medicine (Hebrew) and he has edited the Israel Medical Encyclopedia (10 volumes, 5000 items). He had organized over 20 international congresses in autoimmunity. He is the editor-in-chief for Journal of Autoimmunity along with M. Eric Gershwin (University of California, Davis). According to the Journal Citation Reports, the journal has a 2012 impact factor of 8.145, ranking it 11th out of 137 journals in the category "Immunology”. This journal is a peer-reviewed medical journal covering research on all aspects of autoimmunity. It was established in 1988 and is published 8 times per year by Elsevier.

Abstract:

The lecture will be based on the recent book An Epidemic of Absence – A New Way of Understanding Allergies and Autoimmune Disease by Moises Velasquez-Manoff. It will describe the bilateral interaction between environmental factors and especially viruses, bacteria and helminthes and induction of autoimmune diseases in genetically predisposed subjects. The lecture will also delineate the effects of these infecting agents in presenting autoimmunity along with historical and geoepidemiological facts. 1: The incidence of autoimmune diseases increases the further you are from the equator. 2: Autoimmunity emerged in Sardinia and the USA when the helminthes were eradicated. Multiple sclerosis was the first disease to be treated and ameliorated following supplements of various helminthes. There are several experimental models from colitis to EAE from type 1 diabetes to CIA which were successfully treated by supplementation of helminthes and helminth products. The next stage was the implementation helmintheggs, especially of helminthes whose final host is the pig rather than the human being. It seems that the final step on harnessing the absence to treat the epidemic is synthetic molecules which resemble the active site on the helminth and the eggs which leads to cytokine shift on TH1 to TH2 and induces increase in the number and activity of T-regulatory cells. We will refer to two such molecules based on either similarity or including the phosphorylcholine compound with successful results in collagen induces arthritis, SLE and experimental colitis. These compounds might be a future avenue of ameliorating or even preventing diverse autoimmune diseases.

Biography:

Mahesh Mohan received his Veterinary Medicine degree from the Madras Veterinary College, India, a masters from the University of British Columbia and a PhD from Oklahoma State University, Stillwater, Oklahoma. Soon after completing his post-doctoral training at the Tulane National Primate Research Center he was promoted to Assistant Professor (tenure track). Dr. Mohan’s research is currently funded by R01 grants from the National Institute of Diabetes, Digestive and Kidney diseases and National Institute on Drug Abuse and is focused on the molecular pathogenesis of HIV/SIV in the gastrointestinal tract.

Abstract:

Background: The gastrointestinal (GI) tract is a major site of viral replication, CD4+ T cell depletion, viral dissemination and reservoir formation. Chronic GI inflammation, a hallmark of progressive HIV/SIV infection is associated with disruption of the intestinal epithelial barrier leading to microbial translocation and contributing to localized and systemic immune activation/inflammation which drives AIDS disease progression. While most of our knowledge regarding regulation of inflammation has come from protein regulators such as proinflammatory cytokines, transcription factors, chromatin modifying enzymes and so on, recent evidence suggests critical roles for small non-coding regulatory RNA molecules called microRNAs (miRNAs)that regulate gene expression through post-transcriptional gene silencing in controlling and managing certain aspects of the inflammatory process. Methodology: To understand their immunoregulatory role in the GI tract we collected serial resection segments (6-8 cm) from the jejunum before and again at 21, 90 and 180 days post SIV infection (DPI)of rhesus macaques and separated the different mucosal compartments (epithelium, lamina proprialeukocytes (LPLs), intraepithelial lymphocytes and fibrovascularstroma). Using TLDA microRNA arrays,qRT-PCR, luciferase reporter assays and ISH/Immunofluorescence methods we investigated changes in miRNA expression and characterized specific differentially expressed miRNAs exclusivelyin the LPLs. Results: At 21DPI, ~21 and 9 miRNAs were up and downregulated, respectively. However, at 90DPI (n=66) and 180DPI (n=44), ≥75% of differentially expressed miRNAs showed decreased expression. Additionally, several T-cell activation associated miRNAs (n=6) showed significantly decreased expression at 90 and 180DPI. Interestingly, theSIV-induced miR-190b showed elevated expression at all threetimepoints and confirms our recently published studies demonstrating its expression to be induced in response to viral replication and not by the accompanying immune/inflammatory responses (Mohan M et al. 2014; Journal of Immunology).At 180DPI, among the small number of upregulatedmiRNAs was a lipopolysaccharide (LPS)-responsive miRNA that showed increased expression in the LPLs. The elevated expression of this miRNAwas confirmed in primary intestinal macrophages following in vitroLPS treatment. Furthermore, using luciferase reporter assays we validated two critical signaling transducing components of the TLR4 pathway as direct targets of, at least,two downregulatedmiRNAs. Finally, expression of both downregulatedmiRNAs inversely correlated withprotein levels of the two TLR signaling proteins in the intestinal epithelium and LPLs. Conclusions: To our knowledge, thesestudies for the first time clearly identify miRNA expression signature/s associated with key pathogenic events such as viral replication, chronic immune activation/inflammation and microbial translocation.As miRNAshave been demonstrated to regulate several aspects of the immune response such as immune cell differentiation, migration, cytokine production and TLR signaling, the globa l miRNA down regulation observed in the LPL compartment can potentially disrupt the translational control of proinflammatory signaling molecules and cytokines. In the setting of HIV/SIV infection, such drastic reductions in the LPL miRNAome, although essential to help activated cells mount an immune response, can paradoxically enhance proinflammatory protein translation thereby facilitating proinflammatory signaling, persistent GI inflammation, epithelial barrier disruption, microbial translocation, immune activation and disease progression.

Speaker
Biography:

Trine N. Jorgensen obtained her Ph.D. from The University of Southern Denmark in 2002. She completed her postdoctoral studies at the University of Colorado, Denver Health Sciences Center studying the importance of sex hormones and type I interferon signaling in lupus. In 2007, she joined the faculty at the Lerner Research Institute at the Cleveland Clinic as an Assistant Professor. She has published more than 25 papers and reviews in reputed journals and serves as an ad hoc reviewer for numerous scientific journals.

Abstract:

Systemic lupus erythematosus is an autoimmune disease characterized by elevated production of auto-reactive antibodies and systemic inflammation. Nine out of ten patients suffering from SLE are female. Sex hormones have been extensively studied for their potential effects on disease pathogenesis. It is thus known that testosterone protects while estrogens exacerbate disease development. We have recently described a population of Gr1+CD11b+ cells that are upregulated in male lupus-prone (NZB x NZW)F1 mice. These cells are driven by testosterone in a dose-dependent manner, as revealed by castration and hormonal reconstitution studies. Interestingly, although Gr1+ cells from both male and female prepubescent (NZB x NZW)F1 mice are immunosuppressive, the suppressive capacity is driven by different mechanisms and only male-derived cells remain immunosuppressive after puberty. In support hereof, adult 9 week old male mice depleted of Gr1-expressing cells develop increased levels of antibodies to both thymus-dependent antigens (NP-CGG) and nuclear auto-antigens, while a similar depletion strategy in age-matched females had no effect on either NP-specific antibody production or the spontaneous appearance of anti-nuclear autoantibodies. Further studies revealed that Gr1+ cell depletion in adult (NZB x NZW)F1 male mice resulted in increased levels of TFH and GC B cells after immunization. We conclude that a population of testosterone-driven Gr1+ cells present in (NZB x NZW)F1 lupus-prone male mice exert a hitherto unappreciated role in controlling activation of the adaptive immune system and the development of lupus-like disease. Manipulation of these cells represents an interesting new target for immunotherapy in autoimmune disorders with a female predominance.

Break: Coffee Break 10:40-10:55 @ Foyer

Zia Rahman

Penn State University College of Medicine, USA

Title: Title: The role of TLR7 in spontaneous germinal center formation and the development of autoimmunity

Time : 10:55-11:15

Biography:

Zia Rahman received hisMD from Beijing University in 1993, PhD from National University of Singapore in 2002 and completed postdoctoral studies at Thomas Jefferson University in Philadelphia in 2006. He is an Assistant Professor in the department of Microbiology and Immunology at Penn State College of Medicine. His research focuses on understanding the mechanisms of loss of peripheral B cell tolerance in an autoimmune disease SLE (systemic lupus erythematosus).

Abstract:

Spontaneous germinal center (Spt-GC) B cells and follicular helper T cells (Tfh) generate high affinity autoantibodies involved in the development of systemic lupus erythematosus (SLE). Toll like receptors (TLRs) play a pivotal role in SLE pathogenesis. While previous studies have focused on theB cell intrinsic role of TLR-MyD88 signaling on immune activation, autoantibody repertoire and systemic inflammation, a thorough investigation of the mechanisms by which TLRs control the formation of Spt-GCs remains unclear. Using non-autoimmune C57BL/6 (B6) mice deficient in MyD88, TLR2, 3, 4, 7 or 9, we identified B cell-intrinsic TLR7 signaling as a prerequisite to Spt-GC formation without the confounding effects of autoimmune susceptibility genes and the overexpression of TLRs. TLR7 deficiency also rendered autoimmune B6.Sle1b mice unable to form Spt-GCs, leading to markedly decreased autoantibodies. Conversely, B6.yaa and B6.Sle1b.yaa mice expressing an extra copy of TLR7 and B6.Sle1b mice treated with aTLR7 agonist had increased Spt-GCs and Tfh. Further, TLR7/ MyD88 deficiency led to compromised B cell proliferation and survival after B cell stimulation both in vitroandin vivo. In contrast, TLR9 inhibited Spt-GC development. Our findings demonstrate an absolute requirement of TLR7 and anegative regulatory function for TLR9 in Spt-GC formation under non-autoimmune and autoimmune conditions. Our data suggest that, under non-autoimmune conditions,Spt-GCs initiated by TLR7 produce protective antibodies. However, in the presence of autoimmune susceptibility genes TLR7 dependent Spt-GCs produce pathogenic autoantibodies. Thus, a single copy of TLR7 in B cells is the minimal requirement for breaking theGC-tolerance checkpoint.

Speaker
Biography:

Shamala Devi Sekaran obtained her Bachelor’s degree, Masters Degree and Doctorate in University of Malaya and have been working at the University of Malaya from 1976, as a tutor, then as a lecturer and currently a Professor in Microbiology and Immunology. Her initial duties centered on immunology but rapidly expanded to cover virology, bacteriology and diagnostic microbiology. To date, she has had 40 postgraduate students of whom 37 have successful graduated. There are 148 peer-reviewed publications in academic journals, 2 book chapters and holds the rights of 17 intellectual properties at both levels. In the field of dengue she has published more than 40 papers and is currently involved in a number of projects which include epidemiological and immunological profiling of clinical dengue suspected patients, siRNA and synthetic AMPs for the development of anti-dengue viral peptides, development of diagnostics assays targeting the prM and envelope regions of dengue virus and probable mechanisms of vascular leakage.

Abstract:

Background: Dengue imposes serious healthcare, economic and social burden, with 390 million cases estimated annually, of which 75% are mild or asymptomatic cases. While many factors have been postulated in the pathogenesis of dengue, it has been traditionally believed to be an immune-mediated disease leading to endothelial dysfunctions. This study describes the cytokine levels of a dengue cohort in a Malaysia and investigates the protective immune correlates in clinically asymptomatic household members. Methodology and results: Dengue-suspected patients and accompanying household members (no physical signs of illness) were recruited with informed consent. Clinical data information was obtained and dengue laboratory diagnostics (RT-PCR, MAC-ELISA, NS1 ELISA and HI) were conducted. Serum of patients (dengue positive or presumptive) was subjected to multiplex cytokine analyses while the dengue positive/presumptive household members were gene profiled to find protective immune correlates. Twelve cytokines namely IL-5, IL-10, IL-13, IFN-γ, MIF, IL-8, CCL11, CXCL10, IL-7, FGF-2, ICAM-1 and VCAM-1 were significantly differentially expressed at the different phases of illness in dengue patients. On the other hand, among 29 asymptomatic household members who were found to be dengue positive/ presumptive, cytokine-related genes including TNF-α, IL8, IL2, IL3, IL4, IL5, IL8, IL9, IL10 and IL13, IL18 were found to be down-regulated while CCL5, MIP-1α, MIP-1β, TGF-β were up-regulated. At the same time, a number of matrix metalloproteinase (MMP) members, such as MMP8, MMP10, MMP12, MMP15, MMP16, MMP24 and TIMP1 were significantly modulated. The involvement of these cytokine and MMPs indicate the endothelium as a major player in dengue pathogenesis. This was then demonstrated via in vitro infection of the brain and lung microvascular endothelial cells where both were found to be susceptible to dengue virus infections. Further investigations into the protein expression of dengue-infected microvascular cells reveal that various tight junctional proteins (ZO-1, Claudin-1, Occludin and ESAM) were modulated differentially. Conclusion: Here, we re-iterate findings from other studies to show that cytokine storms are a significant component in dengue immunopathogenesis whereas subclinical infections reveal broad down-regulation many innate, adaptive cytokines and matrix metalloproteinases. This led to the hypothesis where the endothelium is suggested to play an important role. In this study activation of the endothelial cells seemed to have occurred immediately upon dengue infection and is regulated differentially in different organs. This is postulated to trigger the various cascades of immune response as noted in dengue patients. As endothelium dysfunctions are often reversible, this may provide avenues for development potential pharmacologic agents to manage disease severity.

Josef Bodor

Institute of Experimental Medicine, Czech Republic

Title: Hematopoietic-stem-cell based therapy for HIV disease

Time : 11:35-11:55

Speaker
Biography:

Josef Bodor received his Ph.D. (1990) with honors from Institute of Molecular Genetics in Prague, Czech Republic. As of 2013, he is a Senior Investigator working at the Institute of Experimental Medicine in Prague, Czech Republic. Dr. Bodor is a senior scientist with faculty experience from Ivy League Institutions in US hosting on sabbatical leaves around the world (Harvard University Boston, MA, Columbia University; New York, NY, Kyoto University, Kyoto, Japan, Würzburg University, Würzburg, Germany, and Johannes Gutenberg University in Mainz, Germany). Dr. Bodor as an Associate Member of Transregio 52 published series of original reports summarized in an authoritative review which forms a basis for further exploration of the role of cyclic adenosine monophosphate (cAMP) in suppressive function of regulatory T cells (Tregs) and their role in gp120-mediated amelioration of graft versus host disease (GvHD) after hematopoetic stem cell (HSC) transplantation of cells harboring CCR532 mutation.

Abstract:

Our goalsare to develop insight and understanding of the effect of deleting the chemokine receptor CCR5in T cells important for HIV entry and its interplay with immune regulation in HIV, forming basis for a novel technology platform to cure HIV disease. A major innovation is the use hematopoeticstem cell (HSC) transplantation of the cells resistant to HIV such as CCR5∆32 cells, which do not express CCR5 due to a deletion in the promoter. The mutation spontaneously occur in 4-15% of the European population (with frequency remarkably increased in North), confer resistance to HIV in homozygous individuals and could cure HIV disease based on the outcome of bone marrow engraftment in HIV patients with leukemia using a CCR5∆32 homozygous donor.However, patients receiving a bone marrow allotransplantation often suffer from graft-versus-host disease (GvHD),and for that reasonHIV infection is not considered an indication, unless leukemia warrants transplantation. To advance this field, it is,however,vital with i) mapping of donors in bone marrow registries to identify CCR5∆32 donors for world-wide matching to HIV+ leukemic recipients; ii) to advance strategies to understand immune dysfunction and immune regulation in HIV and be able to offer suppression of GvHDand iii) to explore function of CCR5∆32 T cells and the possibility to manipulate CCR5 in stem cells moving towards future autotransplantion of CCR5 deleted hematopoetic stem cells. Our approach is to first screen Registries of Bone Marrow Donors in Norway and the Czech Republic and identify donors homozygous for ∆32 mutation. Secondly, in order to ameliorate GvHD, we intend to exploit mechanism of inhibition of interleukin-2 (IL-2) gene expression, which plays a crucial role in repression of CD4+Tconventional cells (Tcons) by naturally occurring CD4+CD25+Tregulatory cells (nTregs). Transfer of cyclic AMP (cAMP) from nTregs to Tcons and/or its receptor-mediated induction in adaptive Tregs underpins function of potent transcriptional repressor termed Inducible cAMPEarly Repressor (ICER) leading to suppression of IL-2 synthesis thus reflecting potential suppressive function of T cells during GvHD. Further understanding of the mechanisms of immunological self-tolerance will also provide insights into how strong immune responses such as graft rejection could be restrained and engraftment of HIV resistant cells in HIV+leukemic patients could be augmented.

Biography:

Tamer I Mahmoud joined MedImmune as a postdoctoral fellow in 2012. Working with the Autoimmunity group he is characterizing the events that initiate or exacerbate chronic inflammation in the salivary glands of a mouse model of primary Sjögren’s Syndrome. Tamer’s experience in autoimmunity is complemented by his long standing interest in studying the diversity of the B cell repertoire as well as cell subsets that respond to blood-borne pathogens. Tamer received his B.Sc. in Pharmaceutical Sciences from Cairo University. In 2009, he earned his PhD from the University of Alabama at Birmingham

Abstract:

Primary Sjögren’s syndrome (pSS) is an autoimmune disease that is characterized by autoantibodies (autoAbs). Longitudinal data demonstrate that pre-symptomatic autoAbs arise years to decades prior to the diagnosis of pSS. Understanding the underlying mechanisms and delineating if an early life window exists where autoAbs can be inhibited is critical for disease intervention. pSS is closely modeled in non-diabetic NOD.H2h4 mice where we detect autoAbs months before the neogenesis of salivary gland (SG) tertiary lymphoid structures and xerostomia. Importantly, shortly prior to the emergence of autoAbs, spontaneous splenic germinal centers (GC) appear early in life. To determine if SG ectopic follicles and autoAbs arise from spontaneous splenic GC early in life, GC’s were disrupted by a single administration of anti-CD40L mAb at 4 weeks of age. Blockade of CD40/CD40L interaction effectively disrupted splenic GC for over 2 months. Moreover, loss of GC in the spleen was followed by a dramatic loss of SG ectopic follicle development in aged mice. Notably, a single administration of anti-CD40L at 4 weeks of age significantly inhibited autoAb titers. However, no effect on autoAb was observed if a single dose of anti-CD40L was given at 5 weeks of age. Our findings highlight the contribution of immune dysregulation to the development of organ-specific autoimmune disease. Furthermore, these data demonstrate that early prophylactic intervention can inhibit auto Abs and ectopic lymphoid structures in an animal model of pSS.

Speaker
Biography:

Ildikó Molnár MD has completed her PhD at the age of 39 years at the candidate of science course (PhD) of Hungarian Academy of Science. Work and research connected her to Kenézy County and Teaching Hospital from 1977 to 2008. Now she is the chief of EndoMed, Immunoendocrinology, Private Outpatient Clinic from 2008. She is an expert in ELISA, Western and ECL blottings, colorimetric iodine measurement, as well as in allergy testing and bone density measurement with Hologic DEXA. She has published more than 48 papers in reputed journals, 16 chapters and 2 books.

Abstract:

Our previous results demonstrated a/ an association with increased total IgE levels and b/ high IL-5 serum levels in hyperthyroid Graves’ ophthalmopathy; c/ The balance shift of IL-12 to IL-5 during methimazole therapy represented a remarkable difference between patients with the presence and absence of ophthalmopathy. Other authors found an influencing effect of elevated IgE levels on the lower remission rate of Graves’ hyperthyroidism through the smaller declined TRAK values. I argue, that the presence of allergic events does not only influence the remission rate but also may play an inducing factor for thyroid autoimmunity. Allergy was studied in Graves’ disease, Hashimoto’s thyroiditis and euthyroid goiter using AllergyScreen test for 20 aeroallergens and 20 foodallergens. Thyroid hormones (TSH, FT4, FT3), autoantibodies against thyroid peroxidase (anti-TPO), thyroglobulin (anti-Htg) and TSH receptor (TRAK) were measured. A high frequence of sensitized Graves’ and Hashimoto’s patients was found showing age-related decrease in sensitization, even though some of these patients had no clinical signs of allergy. Sensitized Graves’ patients represented a larger allergen spectrum connecting with hyperthyroidism and seasonality, as well as higher values of allergen-specific IgE levels. All plantain and mugwort sensitized patients were also TRAK positive. Soyabean-specific IgE levels demonstrated a strong connection to elevated anti-TPO levels and Graves’ ophthalmopathy. Recently, data on mugwort-specific all immunoglobulin isotype levels (IgG,A,M,E) suggest their inducing role for TSH receptor antibodies via antigen mimicry in Graves’ hyperthyroidism. Summarized, increased aeroallergic sensitization was demonstrated in autoimmune thyroid diseases, particularly in Graves’disease, which may influence the thyroid autoimmunity.

Baochi Liu

Shanghai Public Health Clinical Center Affiliated to Fudan University, China

Title: Classify and risk analysis of surgical patients with HIV infection

Time : 12:35-12:55

Speaker
Biography:

Baochi Liu received his Ph.D. from Zhengzhou University in 2007. He received his B.S.in 1983. He has many Peer-reviewed Publications in reputed journals. His research interest includes general surgery, surgery infection and trauma. He is currently working as a Director and Professor in Department of Surgery, Shanghai Publical Health Clinical Center Affiliated to Fudan University, Shanghai, China.

Abstract:

Object: To explore the classify and risk analysis of surgical patients with HIV-infection. Methods: Retrospective analysis the clinical data of 803 HIV-infected patients who have been operated at Shanghai Public Health Clinical Center and at Henan Infectious Hospital from January 2011 to February 2014.The patients were divided into general surgery, urological surgery, orthopaedics surgery and other special surgical groups according to the classify of operation. The patients CD4, CD8, CD4/CD8, WBC, Plate, Hemoglobin were compared. Results: There were 658 cases of general surgery (81.94%),71 cases of orthopaedics surgery(8.48%), 42 cases of urological surgery(5.32%), 32 cases of other special surgical operation. There were 217 cases with postoperative sepsis (morbidity 27.27%). 16 cases died within 30 day after operation (mortality 2%) The patent’s CD4, CD8, CD4/CD8, WBC, Plate, Hemoglobin was significantly lower in sepsis group compare with in no sepsis group. Conclusion: The most common operation for the patient with HIV infection is general surgery. Follows orthopedics surgery, urological surgery and other special surgery. The lower CD4, CD8, CD4/CD8, WBC, Plate and Hemoglobin are risk facts of postoperative sepsis.

Break: Lunch Break 12:55-13:40 @ Eden’s Landing Restaurent
Speaker
Biography:

I completed my MD degree at University of Debrecen, Hungary in 2011 and I work as a PhD student and trainee in Internal Medicine at Division Of Clinical Immunology, Department Of Internal Medicine, University of Debrecen. Now I also work in clinical practice and I’m doing my research project examining epidemiological characteristics, clinical features, outcomes, laboratory findings including pathogenesis, outcome assessment, or treatment responses in Idiopathic Inflammatory Myopathies. During the past 3 years approximately 10 publications were submitted to Hungarian and international journals. I also work in collaboration with international study gropus in Myositis research (EuMyonet and IMACS).

Abstract:

The idiopathic inflammatory myopathies (IIM) are systemic autoimmune disease, which is caused by an immune-mediated inflammation and characterised with proximal muscle weakness. Myositis-specific auto-antibodies (MSAs) are associated with the disease and can be detected in patients’ sera. These MSAs determine subgroups which are different in symptoms, severity, prognosis and genetic background. During the recent development in knowledge about auto-antibodies the roles of MSAs in diagnosis and prognosis have changed. Anti-TIF1y autoantibody is presented as a tumor-specific MSA led to a 155-kDa/140-kDa protein complex and also showed an association with serious juvenile and adult DM. The association of malignant diseases with myositis is also well known. Risk for tumor in dermatomyositis (DM) is 3-fold, and 1.3-fold in (PM). Based on these data, searching malignancy is one of the most important steps after myositis diagnosis. During this research our aim was to determine the clinical characteristics associated with the presence of anti-TIF1y antibodies and to define the serological subgroup in cancer-associated (CAM) myositis, particularly the tumor specificity and of the mentioned antibody. Patients were caring by the Division of Clinical Immunology, Institute of Internal Medicine, University of Debrecen. We examined 202 patients with IIM. Inclusion criteria was the presence of finished antibody testing, 12 cases showed positivity in anti-TIF1y. One of these patients had CAM. We examined the differences between the anti-TIF1y positive (n=12) and negative CAM (n=51) groups concerning symptoms, lab values, cancer type. The anti-TIF1y antibody positivity have been presented in 5,9% of our patients and associated with severe skin symptoms. Although earlier studies claimed that CAM patients are similarly characterized by severe skin symptoms, in our cohort respectively prevalence of Gottron’s sign and Heliotrop rash were significantly higher in anti-TIF1y positive cases. This research could not prove the tumor-specificity of anti anti-TIF1y antibody, but our results confirm that the presence of this antibody separate a subgroup of myositis different in clinical symptoms and severity. This research was organized within the following program: TÁMOP 4.2.4.A/2-11-1-2012-0001 National Excellence Program—local convergence program providing personnel support in the development and operation for students and researchers. The project was funded by the EU and the European Social Fund. The autoantibody analysis was sponsored by the ESF EuMyoNet Research Networking Programme.

Min Fang

Chinese Academy of Sciences, China

Title: Memory NK cells during mousepox infection

Time : 14:00-14:20

Speaker
Biography:

Fang graduated from Lanzhou University in 1994 and received her Ph.D from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences in 2003. She got her postdoctoral training at Fox Chase Cancer Center from 2003 to 2008. She worked as a research associate and then as a staff scientist at Fox Chase Cancer Center from 2008 to 2012. She joined the Institute of Microbiology, CAS as a professor supported by “Thousand Young Talents Program” of the China’s government in 2012.

Abstract:

Although traditionally classified as cells of the innate system, recent studies have shown the NK cells generate antigen-specific memory during viral infection or vaccination, and protect against subsequent viral infections. We recently discovered that CD94-NKG2E, another NK cell activating receptor, recognize ectromelia virus infected cells in the context of the non-classical MHC class I molecule Qa-1b. We want to detect anti-ECTV specific NK cell memory during viral infection.In the long term, we also want to explore the molecular and cellular mechanisms involved in the generation and maintenance of NK cell memory, relevant to development of vaccination strategies.

Speaker
Biography:

Moses Nnaemek Alo was born in 20th November, 1966 in Ebonyi State, Nigeria. He studied Microbiology (B.Sc.) from University of Lagos, Nigeria. He went further to study Medical Immunology in Masters Degree (M.Sc.) from Ebonyi State University, Nigeria and also obtained a PhD in Medical Microbiology from Ebonyi State University, Nigeria. He also has a professional qualification in Medical Microbiology registriable with Medical Registration Council of Nigeria His research areas include infectious diseases, public health, immunology and medical bacteriology and virology. He has been the Head of Department of Medical Laboratory Science from 2007-2011 at Ebonyi State University, Nigeria, member Medical Laboratory Science of Nigeria, and currently the program coordinator Microbiology in Federal University Ndufu-Alike Ikwo, Nigeria. He is involved in various researches both at undergraduate and postgraduate level. He is currently a research coordinator in Microbiology and Epidemiology of Water Borne Infectious Disease in Federal University Ndufu-Alike Ikwo, Nigeria. He has over 50 publications to his credit.

Abstract:

In endemic regions of sub-Saharan Africa, malaria during pregnancy is a major public health concern and has important consequences on birth outcome. There are extensive and delicate alterations in the immunohematological parameters of pregnant women infected with malaria parasites. This work is designed to ascertain the impact of malaria on immunohematological parameters of pregnant women infected with malaria visiting Federal Teaching Hospital Abakaliki. Out of the 1,500 pregnant women screened for malaria, 660 (44.0%) were positive for malaria parasite. Of the 44.0% pregnant women positive for malaria parasite, the age range of 26-30 years (31.8%) were more infected with malaria parasite, followed by 21-25 years (22.7%), while 41-45 (4.4%) years were the least infected. Pregnant women with no formal education were most infected (36.4%), followed by primary education (27.3%), while secondary education showed the lowest rate of malaria in pregnancy (13.6%). Housewives (29.5%) reported the highest cases of malaria in pregnancy, while students reported the lowest (9.2%). Married women showed the highest cases of malaria in pregnancy (79.5%), while widow reported the lowest (2.3). Christian reported in the highest cases of pregnancy in malaria (75.0%) and Muslim the least (25.0%). The mean values of the immunohaematological parameters of pregnant women with respect to parasitaemia were heamoglobin (9.78±37.45 g/dL), packed cell volume (31.56±2721.14 %), white blood count (8.58±50.06X103/mm2), neutrophils (57.96±1004.97%), Lymphocyte (28.24±1392.97%), mesophils (7.28±110.49%), eosinophils (3.62±1156.91%) and platelets (141.88±133873.07x109/l). This study have shown that the adverse consequences of malaria in pregnancy has great impact on immunoheamatological parameters which may affect not only the neonate and infant but also increase the risk of non communicable diseases when the child grows into an adult and the risk of low birth weight in the next generation.

Vital MS Kalumba

Mediclinic Gynaecological Hospital, South Africa

Title: Is the rate of preeclampsia affected by HIV/AIDS : A retrospective case-control study

Time : 14:40-15:00

Speaker
Biography:

Born on 14 November 1970 in Lubumbashi (DR Congo). The primary and secondary educations were completed at Tuendelee and Enano schools repectively. In 1996, we obtained our Medical Degree from the Medical School of the University of Lubumbashi ( UNILU). The Postgraduate training in Obstetrics & Gynaecology was done at Nelson Mandela School of Medicine, University of KwaZulu Natal in Durban, South Africa. I am currently working as a Gynaecologist at Mediclinic Gynaecological Hospital in Pretoria, South Africa. My areas of interest are: Endoscopic surgery and Preeclampsia.

Abstract:

Objectives: To evaluate the prevalence of HIV/AIDS (and CD4 levels) in women with preeclampsia in comparison to the control group without preeclampsia Methods: This was a retrospective case-control study conducted in South Africa. Data were collected from a tertiary and a regional hospital in the Province of KwaZulu Natal. The hospital records of women who delivered from 1st January 2008 to 30thJune 2010 were reviewed. Cases of preeclampsia which metthe inclusion criteria were analyzed. Their HIV infection rate and profile were compared to that of a control group consisting of women without hypertension in pregnancy. Results: Among 492 cases of preeclampsia, 130 (26.4%) were HIV positive. In the control group, 183/500 (36.6%) were HIV positive (p=0.001 OR=0.62 with 95% CI 0.47-0.82). After adjustment to match the difference in maternal age and parity,p=0.005 and 0R=0.658. Conclusion: The rate of HIV/AIDS was significantly lower in women with preeclampsia when compared to the control group without preeclampsia. HIV positive women 34.2% less likely to develop preeclampsia than HIV uninfected women.

Speaker
Biography:

Ljudmila Stojanovich received her PhD in Medicine, with the thesis “Neuropsychiatric manifestations in patients with Systemic Lupus Erythematosus” in 1999. She is the scientific director in the Bezhanijska Kosa, University Medical Center of Belgrade University, where she is currently a Research Professor. Her research focuses on Systemic Lupus Erythematosus, Antiphospholipid Syndrome, and Vaccination in patients with Autoimmune Rheumatic diseases. She is an author of three monographs and of about 250 articles on various aspects of Rheumatic disorders, published in international and domestic journals and in conference proceedings. She is in Editorial Boards/Reviewer in the “Current Contests” or “Science citation index”, like Lupus, Cellular and Molecular Neurobiology, The Journal of Vaccine, The Journal of Rheumatology, Allergologia et Immunopathologia and others. She is a member of number International Project, like of “the European Forum on Antiphospholipid Antibodies”, “Multicentre Studies Antiphospholipid Antibodies, Infections and Autoimmune Diseases”. She is a mentor/Supervisor of a numbers of post-doc students.

Abstract:

Introduction: Antiphospholipid syndrome (APS) patients suffer from various cardiovascular manifestations with the presence of antiphospholipid antibodies (aPL). APS may manifest itself as a primary disease (PAPS) or as a secondary disease, most commonly in the context of Systemic Lupus Erythemathosus (SLE). Patients and methods: We analyzed 488 patients: 346 PAPS and 142 patients with secondary APS (398 female and 90 male, 45.03±13.61 years). aPL analysis included analysis of aCL (IgG/IgM), ß2GPI and LA. In all patients echocardiography study was performed in order to reveal presence of pseudoinfective endocarditis or valve thickening or dysfunction not related to age. Results: In our study group, there was 38.7% pts with aCL IgG antibodies, 53.1% with aCL IgM, 34.1% with ß2GPI IgG, 41.8% ß2GPI IgM and 53.2% with LA. There was no statisticaly significant difference between overall cardiac manifestations and the type of aPL. Highly statistically significant difference was revealed considering presence of aCL-IgG and aCL-IgM antibodies and pseudoinfective endocarditis (p=0.004, p=0.003 respectively) and presence of aCL-IgG and valvular dysfunction (p=0.023). Valvular manifestations in our cohort were significantly related to titers of aCL antibodies. The level of aCL IgG (p=0.005, Pearson +0.138) were in positive correlation with presence of pseudoinfective endocarditis. Conclusion: Our study showed that presence of anticardiolipin antibodies in APS patients brings higher probability of valvular changes development. Higher titers of aCL IgG bring greater probability of pseudoinfective endocarditis development in our APS cohort.

Speaker
Biography:

Marlous Dillingh has a background in biomedical sciences. She is currently in training as a clinical pharmacologist at the Centre for Human Drug Research, Leiden, The Netherlands. Her main expertise is the integration of inflammation/immunology and pharmacology, applied in early phase clinical drug development, which is the focus of her PhD education.

Abstract:

Human in vivo models of systemic inflammation are used to study the physiological mechanisms of inflammation and the effect of drugs and nutrition on the immune response. Although in vivo lipopolysaccharide (LPS) challenges have been applied as methodological tool in clinical pharmacology studies, detailed information is desired on dose-response relationships, especially regarding LPS hyporesponsiveness observed after low-dose in vivo LPS administration. A randomized, double-blind, placebo-controlled study was performed with single ascending low doses of LPS (0.5-2 ng/kg body weight) to assess the in vivo inflammatory effects of low intravenous LPS doses, and to explore the duration of the induced LPS hyporesponsiveness assessed by subsequent ex vivo LPS challenges in healthy volunteers. The in vivo inflammatory response showed a dose-dependent increase in body temperature, heart rate, CRP and circulating cytokines (TNF-α, IL-1β, IL-6, IL-8) which showed clearly distinctive increases from placebo already at the lowest LPS dose level tested (p≤0.0001). Ex vivo LPS challenges were performed to estimate the duration and magnitude of LPS hyporesponsiveness by assessment of cytokine release. In vivo LPS administration dose-dependently induced a period of hyporesponsiveness in the ex vivo LPS-induced cytokine release, with maximal hyporesponsiveness observed at 6 hours, lasting no longer than 12 hours. For IL-6 and IL-8, indications for immune cell priming were observed. This study expands the knowledge about the dose-effect relationship of LPS-induced hyporesponsiveness. As such, the low-dose LPS challenge has been demonstrated to be a feasible methodological tool for future clinical studies exploring robust pharmacological or subtle nutritional immune-modulating effects.

Biography:

Dianne Lorton completed her PhD in Neurosciences at Indiana State University in affiliation with Indiana University School of Medicine. She completed Post-doctoral training in pharmacology at Duke University and in neuroimmunology at the University of Rochester School of Medicine. She is currently an Assistant Professor at Kent State University in the College of Arts and Sciences. She has published over 70 papers (manuscripts, reviews, and book chapters) on neuroimmunology focusing on sympathetic nervous system regulation of immunity.

Abstract:

Mechanisms that cause autoimmune disease are complex and include interactions with genetic, environmental, immunologic, and neural-endocrine factors. How tolerance is broken and disease onset is initiated remain enigmatic. These events are often separated by many years, suggesting that disease onset requires a triggering event that if understood, could be targeted therapeutically. Physical and psychological stressors are implicated in the development of autoimmune disease, based on several observations. First, severe life stressors are strongly associated with disease onset in up to 80% of patients. Second, the major stress pathways, the sympathetic nervous system (SNS) and hypothalamic –pituitary adrenal (HPA)-axis function to restore immune system homeostasis after immune challenges and regulate immune responses that become pathological in autoimmune diseases. Finally, there is a common “trifecta” of dysregulated immune functions, elevated SNS activity and low HPA-axis responsiveness across most autoimmune diseases. Understanding the immune-to-nervous system and nervous -to immune system cross-talk that leads to this ‘trifecta” is key to understanding autoimmune disease mechanisms. Here, we focus on findings indicating elevated SNS tone and altered nerve to 2-adrenergic receptor signaling to the immune system are pathological events required for triggering autoimmunity using in an animal model of rheumatoid arthritis as an example.

Break: Coffee Break 16:00-16:15 @ Foyer

Gao Peisong

The Johns Hopkins University School of Medicine, USA

Title: Functional Effects of TGF-beta1 on Mesenchymal Stem Cell Mobilization in Cockroach Allergen Induced Asthma

Time : 16:15-16:35

Speaker
Biography:

Peisong Gao, M.D., Ph.D. is currently Assistant Professor of Medicine at The Johns Hopkins University School of Medicine in Baltimore, Maryland. Dr. Gao received his MD degree and pulmonary medicine training in The Fourth Military Medical University (FMMU), Xi’an, China. From July 1997 to January 1999, he was a visiting research fellow with Dr. Julian M. Hopkin at Osler Chest Unit, Oxford University. He subsequently moved to the University of Wales Swansea with Dr. Hopkin, pursuing a Ph.D. working in molecular genetics of asthma. In 2002, Dr. Gao became a Postdoctoral Fellow with Dr. Shau-Ku Huang in the Division of Allergy & Clinical Immunology at Johns Hopkins University School of Medicine. In 2008, Dr. Gao was promoted to Assistant Professor. Dr. Gao is a member of the Genetics, Molecular Biology and Epidemiology Committee (GMBEC), the American Academy of Allergy, Asthma & Immunology (AAAAI), and the American College of Allergy, Asthma & Immunology (ACAAI). Dr. Gao's research has been greatly recognized by several awards, including the 2004 Research Excellence Award, the 2007 Interest Section Award, and Outstanding Pediatric Allergy, Asthma and Immunology Award from AAAAI.

Abstract:

Mesenchymal stem cells (MSCs) have been suggested to participate in immune regulation and airway repair/remodeling. Transforming growth factor β1 (TGFβ1) is critical in the recruitment of stem/progenitor cells for tissue repair, remodeling and cell differentiation. In this study, we sought to investigate the role of TGFβ1 in MSC migration in allergic asthma. We examined nestin expression (a marker for MSCs) and TGFβ1 signaling activation in airways in cockroach allergen (CRE) induced mouse models. Compared with control mice, there were increased nestin+ cells in airways, and higher levels of active TGFβ1 in serum and p-Smad2/3 expression in lungs of CRE-treated mice. Increased activation of TGFβ1 signaling was also found in CRE-treated MSCs. We then assessed MSC migration induced by conditioned medium (ECM) from CRE-challenged human epithelium in air/liquid interface (ALI) culture in Transwell assays. MSC migration was stimulated by ECM, but was significantly inhibited by either TGFβ1 neutralizing antibody or TβR1 inhibitor. Intriguingly, increased migration of MSCs from blood and bone marrow to the airway was also observed after systemic injection of GFP+-MSCs, and from bone marrow of Nes-GFP mice following CRE challenge. Furthermore, TGFβ1 neutralizing antibody inhibited the CRE-induced MSC recruitment, but promoted airway inflammation. Finally, we investigated the role of MSCs in modulating CRE induced T cell response, and found that MSCs significantly inhibited CRE-induced inflammatory cytokine secretion (IL-4, IL13, IL17 and IFN-γ) by CD4+ T cells. These results suggest that TGFβ1 may be a key pro-migratory factor in recruiting MSCs to the airways in mouse models of asthma.

Xiao-Xia Jiang

Institute of Basic Medical Science, China

Title: Mysm1 epigenetically regulates B1 cell proliferation via targeting miR150

Time : 16:35-16:55

Biography:

Xiao-Xia Jiang has completed her PhD at the age of 28 years from Institute of Basic Medical Sciences. She is an associate professor in the Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences. She has published more than 40 papers in reputed journals.

Abstract:

B1 cells are the dominant population of B cells in the pleural and peritoneal cavities. They are a significant source of serum antibody, and they make a dominant contribution to low-affinity IgM antibodies that are present in serum of unimmunized mice. B1 cells in the mouse are thought to be derived from precursors in fetal liver rather than from adult bone marrow. They are believed to maintain their cell numbers in adult mice by longevity and homeostatic proliferation. Unlike conventional B cells (B2 cells) and despite the importance of B1 cells in protection from infections and their association with autoimmunity, the mechanism of B1 cell proliferation and function remained poorly understood. Mysm1 is a histone deubiquitinase and has been shown to play an essential role in hematopoiesis and lymphocyte development. Our previous study has demonstrated that in Mysm1 deficient mice, B2 cell development is blocked and B2 cell number is significantly lower compared with their counterpart. In this study we found that, in contrast to the dramatically decreased level of B2 cells, the percentage of B1 cells in the spleen and peritoneal cavity of Mysm1 deficient mice was increased compared with that in wild type mice. Mechanistic study has demonstrated that miR150 expression is compromised in B1 cells from Mysm1 deficient mice. Mysm1 controls the transcription of miR150 through regulating the chromatin state of miR150 locus. What’s more, forced expression of miR150 in B1 cells from Mysm1-/- mice can partly rescue the phenotype. Over all, our study, for the first time, reveals the important role of histone H2A deubiquitinase in B1 cell proliferation and development.

Biography:

Myron R Szewczuk received his PhD (Biology and Immunochemistry) from the University of Windsor, Windsor Ontario in 1974 and completed his postdoctoral studies in Cellular Immunology under Dr. Gregory W.Siskind at Cornell University Medical College, New York City, in 1978. From 1978-81, Dr. Szewczuk was an Assistant Professor of Pathology at McMaster University, Hamilton, Ontario. In 1981, he joined the Dept. of Microbiology & Immunology (now Biomedical and Molecular Sciences) as an Associate Professor of Immunology at Queen’s University, Kingston, Ontario. In 1986, he received tenure and became full Professor of Immunology and Associate Professor of Medicine. He is presently a full time faculty member at Queen’s University with an active teaching and research program in immunology and cancer. He has published over 100 papers, chapters and reviews primarily in the field of immunology and cancer.

Abstract:

Toll like receptors (TLRs) are essential sensors of microbial attack, and they orchestrate the innate immune response against many microorganisms. The signaling pathways of these mammalian TLRs are well characterized, but the initial molecular mechanisms activated following ligand interactions with their receptors remain poorly defined. Here, we report a novel signaling paradigm initiated by binding of specific TLR ligands (LPS for TLR4, imiquimodfor TLR7, and CpG for TLR9 ) to potentiate G protein-coupled receptor and matrix metalloproteinase-9 (MMP9) activation to induce mammalian Neu1 sialidase. Central to this process is that Neu1-MMP9 complex is bound to TLR-4, -7 and -9 in naive and ligand stimulated macrophage cells as revealed by co-immunoprecipitation and colocalization assays. Using NFκB dependent secreted alkaline phosphatase (SEAP) analysis, ligand-induced TLR activation was significantly inhibited by oseltamivir phosphate (OP), MMP9 inhibitor and BIM-23127 (a specific NMBR inhibitor). Mal-2 lectin (Maackiaamurensis agglutinin) binding to immunoprecipitated TLRs in cell lysates from naive but not TLR ligand stimulated RAW-blue macrophage cellsindicated the removal of the α-2,3 sialic acid residues from the stimulated receptor ectodomain. OP, MMP9 inhibitor and BIM-23127 blocked MyD88 recruitment to the ligand stimulated TLR receptors. This study reveals an novel identical GPCR signaling platform to potentiate Neu1 and MMP9 cross-talk on the cell surface and in the endosomal compartments of macrophages that is essential for Toll-like receptor activation, cellular signaling and pro-inflammatory responses. Supported by NSERC to MS and CIHR doctoral award to SA.

Speaker
Biography:

Abstract:

To date, no study of the immune responses in cutaneous leishmaniasis caused by L.donovanisensulatoexists has been done. The restriction of a virulent parasite to the skin, instead ofit causing,as expected, a systemic infestation, presents a special situationwhere the body defenses seem to be particularly activated, limiting the invasiveness of this organism.Revealing which form of the immune response is induced in these cases,and the activation level such a response reaches,may lead us,by determining and manipulating thefactors under play here, to full resistance! In the current study, we aim at definingof the two arms of the immune system, of which is induced?Is it the humoral and/orthe cell mediated one?Which oneled to limiting invasiveness?For assessing the magnitude of the humoral response we used micro-ELISA with as antigen a lysate of an L. donovaniisolate(IPTI) and a recombinant copy coded by K39 gene of a Leishmaniachagasiisolate; asfor the Montenegroreaction,one of our isolates was the source of antigen.Serologic tests were carried out on all patients. Theyrevealed anti L. donovaniantibodies in 50% of patients. Montenegro skin test was negative in all patients.Using southern blot genomic DNA, all the isolates exhibited similar restriction fragment patterns and hybridization intensities with probes of the K39 gene. Thelack of response in the patients who were negative in either one of the responses (or in both) may be due to either the concealment of the organisms inside macrophages and thus is delivered in circulation and to different organs in very small numbershence inducing tolerance rather than an immune response ashappens in situations where we desensitize a subject,an established technique, whereby T lymphocytes become tolerant to a specific antigen. This may explain lack of clinical symptoms and signs in cases with sub-clinical infections also referred to as carriers. But before ending, and very importantly it is pertinent to note that this provesthat both anti-parasite antibody levels and skin testing,sometimes, have no value clinically in diagnosing leishmaniasis!Effectively histology of any tissue with a lymphatic component should lead to demonstrating the parasites, an easy, dependable and reliable diagnostic procedure.

Biography:

Abstract:

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of antibodies to components of the cell nucleus in association with a diverse array of clinical manifestations. Polymorphisms in cytokines genes may play an important role in the development and clinical manifestation. Due to this, there is a great interest in the identification of biomarkers that which could quantify the susceptibility and disease activity. A case-control study of 100 lupus cases and 100 lupus-free adult controls was performed to analyze whether or not the polymorphism of the TNF-α gene promoter at positions -308 G/A would alter the risk for SLE and clinical manifestations. Genotyping was carried out by polymerase chain reaction, PCR products were digested by NcoI restriction enzyme and fractionated after on 2% Agarose gel and visualized posteriorly staining by ethidium bromide. There were significant differences in the distribution of the TNF-α genepolymorphism between the SLE and control groups. Individual carriers of the variant allele A had a 3.29 (95% CI: 1.7738-6.1325) -fold increased risk for SLE. Moreover, association was observed between SLE patients and serositis (P=0.0228). This study presents a preliminary evidence of association between TNF-α polymorphism and SLE susceptibility in Egyptians.

Biography:

Ivan Reva graduated Vladivostok State Medical University (Russia) in 2000 year. In 2003 had graduated qualification course on basic and urgent surgery on General Surgery Department of VSMU. In 2004 defend scientific degree in surgical sector. In 2009 had graduated PhD course on the Department of Bacteriology of Niigata University Graduate School of Medicine. From 2009 until 2012 invited expert at the Department of Bacteriology of Niigata University Graduate School of Medicine. From 2012 vice-director of the International Medical Education and Research Center (Niigata, Japan) and Senior Research Scientist of the Far Eastern Federal University (Vladivostok, Russia).

Abstract:

Introduction:
Previously, the author investigated H. pylori infection of the adult patients with gastrointestinal diseases in Vladivostok, far Eastern Russia. In this study, the role of Helicobacter pylori infection in lactase deficiency pathogenesis in children was further investigated. In the pediatric fields, secondary and transient lactase deficiency was seen during clinical practice of different gastrointestinal diseases. Many previous studies have shown the mucosal conditions of small intestine and duodenum in secondary lactase deficiency; however, local immune responses in gastrointestinal tract have not been examined. Especially, conditions of gastric mucosa and epithelium in different pathogenetic variants of lactase deficiency in infants and children under 3 years have not been well studied. In this study, the roles of H. pylori infection and immune responses of gastric mucosa and epithelium in, pathogenetic aspects of lactase deficiency in children under 3 years were investigated.
Methods:
Sixty-three pediatric patients (age: 5 months to 3 years) with different loss of weight in Regional Clinical Center of Maternity, Vladivostok, Russia, were also included during 2008-2011. All patients were diagnosed as lactase deficiency. Morphological changes of gastrointestinal mucosa were examined by endoscopy and dark field microscopy. H. pylori in biopsy specimens was detected by immunostaining CD4-, CD8-, CD 68-, CD163-, or CD204-positive immune cells in the specimens were detected by immunostaining.
Results:
In the previous study, 89.9% of patients (age, 15 to 80 years) were H. pylori-positive, regarding the virulence genotype of H. pylori, 79.4% were cagA-positive. As for EPIYA motif of cagA, ABC type was the most prevalent and accounted for 73.2%; ABCC type for 14.6%; AB or ABCCC type for 4.9%, and novel AAABC type for 2.4%. No ABD type was detected. In this study, 95% of children under 3 years with secondary lactase deficiency were H. pylori-positive. Changes of immune cell; numbers and condition in cellular and humoral immunity according to clinical manifestations of this disease were established. Increase of proliferative activity of immune cells in epithelial layers and the cells without contact to epithelial wall in mucosa were found. Immunostaining showed the increase of immune cells positive for CD4, CDS, CD 68, CD163, and CD204 in gastrointestinal epithelium in H. pylori-positive lactase deficiency patients. Discussion: In the previous study, cagA-positive H. pylori mainly belonged to Western type (EPYIA-ABC type) although Vladivostok is geographically located in East Asia. Present study is the first investigation of lactase deficiency with H. pylori infection in children under 3 years in Vladivostok, Russia. Data suggest mechanisms of pathogenicity of lactase deficiency under H. pylori infection. The data are also useful for development of immune response algorithm during medication of those patients and for monitoring of morphological condition of gastrointestinal mucosa in children during various pathologic processes associated with malabsorption and lactase deficiency. Further investigation is required to reveal the exact mechanisms of lactase deficiency under H. pylori infection.

Biography:

Leonora Hana-Lleshi certified specialized allergologist-immunologist living and working in Gjakova,KOSOVA.The Faculty of General Medicine I’ve finished in 1990-1996 in Craiova,Romania.From 2001-2005 I’ve recived titlle certified specialized allergologist-immunologist in UCCK-Prishtina,Kosova.In that time 6 months I was in UHC”Mother Theresa”Tirana , Albania in training in field of clinical allergology. In 2012 I’ve recived a master degree on medicine science from Ministry of Education Albania (MoES),which has equivalented my diploma of medicine and specialization based in Bologna equivalentation. From 2006 I’m working us a certified specialized allergologist-immunologist in R.H.”ISA GREZDA”Gjakova, Kosova. Till now I’ve represented 4 international poster abstract representations,First in WAC-Munich 2005 ,I was a Travel Grant winner from DGAKI first author and representator of poster abstract No.560;Second representation :first author and poster abstract representator in XXVI Congrex of the European Academy of Allergology and Clinical Immunology, 2007 Goteborg, Sweden abstract No.797,and co-author with Dr.Luljeta Neziri-Ahmetaj poster abstract No.657 in Goteborg 2007,Travel Grant winner to attend Summer School of allergology and immunology organized by EAACI in Cluj-Napoca 2007,Romania; attender of National Simposium of Croatian Society of Allergology and Clinical Immunology in 2009 in Zagreb Croatia.Poster abstract accepted for presentation in 12th EAACI Immunology Winter School on Basic Research in Allergy and Clinical Immunology,2014 Poiana Brasov Romania(abstract titlle:”In vitro testing for discrimining clinical relevance of sensitization to particular allergens.”),4 oral abstract representation in local conferences,supporter of WAD in our local area organizing local conferences supported by GINA. And abstract representator in our 3 national and international conferences. A member of Kosovarian Society of Allergology and Clinical Immunology, EAACI, WAO.ACAAI etc

Abstract:


Introduction:
Being from Kosovo the same us in the other parts of the globe allergy desease are very often represented in our medical institutions. Maybe the procentage is the same us in the Europe or in the other parts of the world. Mostly 1/4 or 1/5 habitants are representing one kind of allergy from mild symptoms to severe life threatening allergy reactions. Us a certified specialized allergologist-immunologist living and working in the small city Gjakova, Kosovo every day in my experience I meet a different kind of allergy to my patients: pollen allergy, food allergy, medication allergic reactions, contact allergy, and insect sting allergy such us bites: bee, wasp etc. In one my case patient I’ve observed that the subject :age 12 years; gender: female allergic in: pollens and bee venom with anaphylactic allergic reaction .Specific Ig- E detected with POLYCHECK(Bio-Check) first analysis are shown us down below: The patient was obtaining only SCIT in bee venom with ANALLERGO vaccine ( Apis mellifera), which has started initial treatment in U.H.C. ”Mother Theresa” Tirana, Albania ,before 2 years with rush method and after maintenance treatment was realized by myself in R.H. ”Isa Grezda” Gjakova till now I’m performing by schematic regimen SCIT and every time the patient is under my observation for 30 minutes. For two years of immunotherapy the patient have supported very good the treatment with moderate local reaction in the beginning and now without any clinical possible adverse reactions. Every application of vaccine was performed deep subcutaneously in the volar side of forearm . After one year of immunotherapy with Anallergo, the patient have repeated Specific Ig-E on pollens and hymenopthera venoms ,the parameters of bee venom have fall down from 5-4;Alder pollen from 1-0;Birch pollen from 2-0;Hazelnut pollen from 2-1;Beech pollen from 2-0;Oak pollen from 2-1;Pine from 2-0;Rhizopus nigrans from 2-0;Grass mix from 3-1 and house dust from 2-0. And concomitantly parameters of bee venom and parameters on pollens began to fall down without ethiological treatment it means without S.I.T on certain pollens.
Conclusion:
The patients which are allergic to bee venom and mostly of them are allergic to pollens too, obtaining SCIT in bee venom can represent and a decrease of parameters in pollen allergy too. It remains to follow and one year the patient analysis and to get a definitive conclusion about the efficiency of bee venom SIT and its correlation of positive influence to pollen allergy.

Break: 17:05-18:30 Poster Presentations

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