Biography:

Katharina Geißler works as ENT Doctor at the ENT Department of the Jena University Hospital and has her expertise in analysis of T cell function in human palatine tonsil and other clinical aspects of chronic tonsillitis and tonsillectomy like pain therapy after tonsillectomy. Actually she works on organ models of nasopharyngeal and palatine tonsils.

Abstract:

Statement of the Problem: Inflammation of the palatine tonsils, an easily accessible secondary lymphoid tissue, is one of the most common diseases in otolaryngology. In context of chronic tonsillitis (CT) and peritonsillar abscess (PTA) the functionality of tonsillar immune cells, notably T cells, is poorly understood.

Methodology & Theoretical Orientation: Patients presenting with CT (n=10) or unilateral PTA (n=7) underwent bilateral tonsillectomy. T cells were purified via automated magnetic selection and were identified by using flow cytometry-based immunophenotyping. In addition, cytokine release for IFNγ, TNF and IL2 was measured.

Findings: Tonsils from CT harbored more regulatory T cells, CD69(+) T cells, PD-1(+) CD4(+) T cells, pointing to T cell exhaustion due to chronic infection. After T cell receptor stimulation, the concentration of released cytokines increased. Higher concentration in tonsil tissue of peritonsillar abscess was measured for TNF und IL2.

Conclusion & Significance: Our study documents differences in tonsillar T cell function between CT and PTA by eliciting specific immunological responses in chronic versus acute settings of inflammation.

Biography:

Ildikó Molnár completed her PhD in the special field of Graves’ ophthalmopathy 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. Her research activities exerted on field of internal medicine, endocrinology, immunology and allergology participating at international congresses gave guest lectures or was invited speaker. Now she is the Chief of EndoMed Debrecen Kft., Immunoendocrinology and Osteoporosis Centre in private outpatient clinic. She is an expert in laboratory methods and DXA measurement. She is interested in the immunoendocrine patho-mechanisms, particularly in Graves’ orbitopathy; allergy in autoimmune thyroid diseases; thyroid hormonal metabolism; postmenopausal osteoporosis. She has published more than 69 papers in reputed journals, 16 chapters and 4 books.

Abstract:

A strong evidence has been demonstrated for an increased risk of stroke in patients with autoimmune thyroiditis. Monocyte chemoattractant protein-1 (MCP-1) plays an active role in vascular disease leading to stroke in consequence of acute thrombosis. The relationship between free thyroxine (FT4) and MCP-1 serum levels was investigated in 72 postmenopausal, 37 obese and 16 healthy, control women without manifest thyroid disease. Serum levels of MCP-1 were measured with enzyme-linked and FT4 with chemiluminescence immunoassays. The results were evaluated according to age, body mass (BMI) index and thyroid gland volume (TGV) of patients. An inverse correlation between FT4 and MCP-1 serum levels was found in the whole group (P<0.018, r=-0.4648), and a positive correlation between FT4 and age (P<0.003, r=0.5177). In detail, MCP-1 levels inversely correlated with FT4 levels in postmenopausal (P<0.01, r=0.5586), and positively with BMI index (P<0.04, r=0.5788) in obese women. In controls, FT4 serum levels showed a strong association with TGV (P<0.02, r=0.7918). MCP-1 serum levels increased in postmenopausal and obese women compared with those in controls (17.46±2.96 and 19.55±3.03 ng/ml vs. 15.93±0.56 ng/ml, P<0.043 and P<0.0001, respectively). Surprisingly, FT4 levels were significantly decreased (13.9±2.58 vs. 15.61±2.81 pmol/l, P<0.003) and MCP-1 levels increased (P<0.01) in obese women compared with those in postmenopausal women. In summary, elevated MCP-1 serum levels are present in postmenopausal and obese women without manifest thyroid disease. MCP-1 levels were inversely associated with FT4 in postmenopausal and positively with BMI index in obese women. In postmenopausal and obese women without manifest thyroid disease, the reduced FT4 serum levels can be regarded as a marker of risk for atherosclerosis via elevated MCP-1 levels.

Biography:

Guochang Hu is an Associate Professor of Departments of Anesthesiology and Pharmacology at the University of Illinois at Chicago. Over the past 15 years, his research has focused on acute lung injury, innate immunity and inflammation, and vascular endothelial permeability. He has established a record of successful and productive research in the areas highly relevant to lung inflammatory injury. He is currently serving as a scientific reviewer of more than 40 journals. He also has served as a grant reviewer for the National Institutes of Health and American Heart Association. He has received numerous teaching and research awards including a Young Investigator Award from the American Heart Association.
 

Lijun Wang is the Chairman of Department of Critical Care Medicine of the Affiliated Hospital of Southern Medical University, China. He has his expertise in the field of critical care medicine, especially in the management of critical maternal near-miss. He has constructed a network including consultation and transfer of critical patients between tertiary referral center and Grade-II hospitals.

Abstract:

Rationale: Uncontrolled inflammatory response in sepsis predominantly contributes to development of multi-organ failure and lethality. However, the cellular and molecular mechanisms for excessive production and release of proinflammatory cytokines are not clearly defined. The purpose of this study is to determine the role of the GTPase Ras-related protein in brain (Rab)1a in regulating the nucleotide binding domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and lung inflammatory injury during sepsis.

Methodology: Human alveolar macrophages were isolated from septic patients. Cecal ligation and puncture was performed to assess lung inflammation. Genetic manipulation of Rab1 expression in murine bone marrow-derived macrophages was conducted by electroporation.

Findings: Rab1a activity was elevated in alveolar macrophages from septic patients and positively associated with severity of sepsis and respiratory dysfunction. In alveolar macrophage-depleted mice challenged with cecal ligation and puncture, pulmonary transplantation of Rab1a-inactivated macrophages by expression of dominant negative mutant Rab1 N124I plasmid dramatically reduced the release of interleukin (IL)-1β and IL-18, neutrophil count in bronchoalveolar lavage fluid, and inflammatory lung injury. Expression of Rab1 N124I plasmid in bone-marrow-derived macrophages prevented the release of IL-1β and IL-18, NLRP3 inflammasome activation, production of pro-IL-1β and pro-IL-18, and attenuated Toll-like receptor 4 surface expression and nuclear factor-кB activation induced by bacterial lipopolysaccharides and ATP compared with control cells.

Conclusion & Significance: Inhibition of Rab1a activity in macrophages resulting in the suppression of NLRP3 inflammasome activation is a promising target for the treatment of patients with sepsis.

Biography:

Alaa Abdelkarim Fouad  is the Founder and Chief Medical Officer of ACE Cells Lab Limited, UK. He is the Consultant in Endocrinology and stem cells therapy Dept.. More than 28 years of experience and served in more than 8 countries. Got the fellowship of Royal Society of medicine, Royal Collage of chemistry, Fellowship of the Malaysian Association of Endocrinology and the International association for stem cells research. Headed the department of endocrinology and Diabetes for more than 8 years treating complications of Diabetes by cellular applications.

Abstract:

The unique mixture of cellular and humoral immunity in rheumatoid arthritis (RA) that leads to activation of osteoclasts which causes the erosion of the bones and the subsequent deformity; this mixture makes RA one of the most difficult conditions to be controlled. The trigger of the inflammatory process starts by synovitis, and all the immunity process is localized in the affected joint(s) as a harmony between the cellular immunity and the cytokines and the humoral immunity. The available treatment to control the immunity reaction is the immunosuppressants to be administered systematically while the main reaction is local reaction. Our philosophy in approaching the various conditions by giving full attention to the regeneration and repair the damage makes us give more attention here the immunity reaction which is the cause of the damage. In the RA immunity reaction we do not intend to suppress the immunity, but to modulate it and give it the proper peptides needed to neutralize the reaction in the joint. Primary research was done to 20 cases, 18 of them continued the primary 3 months course to be declared in this session showing the ability to control the immunity reaction.

Biography:

Gorjana Rackov has her expertise in immuno-oncology and passion for developing innovative therapies and improving healthcare. She obtained her degree in Molecular Biology and Physiology from University of Belgrade, Serbia in 2010 and moved to Spanish National Centre for Biotechnology (Madrid), to study macrophage and T cell activation during infection and autoimmune disease. She completed her PhD thesis, at Autonomous University of Madrid in 2015, unraveled a critical role for cell cycle inhibitor p21 in generation of mROS, production of proinflammatory cytokines and interferons, as well as activation of MAPK and NF-kappa B pathways. Currently, she works as a Postdoctoral Researcher in IMDEA Nanoscience Institute, developing a monoclonal antibody-based immunotherapy for high-grade brain tumors. Her long-term goal is to develop an original research line and pursue a career of independent group leader.

Abstract:

Naive, activated and memory T cells have different metabolic profiles. During TCR activation, mitochondria translocate to immunological synapse and produce reactive oxygen species (ROS) that are essential for correct T cell activation, antigen-specific T cell expansion and IL-2 production. Antigen-experienced memory T cells, especially hyperactivated effector/memory T cells in lupus models, strongly rely on mitochondrial metabolism. Nonetheless, the role of mitochondrial ROS (mROS) in effector/memory T cell functions remains undefined. We showed that, compared with the primary activation of naïve cells, mROS accumulation in re-challenged effector/memory cells occurs much faster and with greater intensity. This suggested that mROS activation plays a critical role in effector/memory T cell activation. In fact, mROS abrogation (using DPI, an inhibitor of ROS-producing mitochondrial complexes) led to complete inhibition of effector/memory T cell phenotype, as seen by down regulation of CD44 expression marker. These findings were corroborated in Fas-deficient T cells isolated from lupus model lpr mice. We found that hyperactivation of lpr effector/memory T cells, associated with elevated production of IFN-gamma (a key cytokine associated with disease development in lupus models), was accompanied by increased mROS activation in these cells. In addition, mROS abrogation led to a significant decrease in CD44^hi lpr effector/memory T cell accumulation and their hyperactivation status. Overall, our data point to mROS as key regulator of effector/memory T cell functions, and its pharmacological modification may serve as a potential target for treatment of autoimmunity.

Biography:

Maren Jannasch is an expert in Tissue Engineering and has a passion in modelling immune responses in vitro. Her biomimetic 3D model based on blood-derived macrophages in a 3D wound matrix creates new pathways for the improvement of in vitro biomaterial tests. She has built this model after five years of experience in academic research, presently at the Translational Center Regenerative Therapies located in Wuerzburg (Germany).

Abstract:

After implantation of a medical product, the success of a therapy strongly depends on the host-initiated immune reaction (foreign body reaction). For the risk assessment of a medical product, the inflammatory reaction and the soft tissue reaction is standardly assessed after implantation in animals. In vitro tests on the interaction with blood components such as immune cells complement the gold standard. However, a poor correlation between in vitro and in vivo assessments slows the reduction of animals’ burden in science. Our research focuses on the development of biomimetic 3D tissue models, which should be applied as time- and cost-efficient biomaterial screening platform. Differences between species strengthen our efforts to construct based on human macrophages and fibroblasts immune competent 3D models. In a comparative study, comprising clinical scenarios such as lipopolysaccharide contamination or the presence of IL-4, a statistical model of multi-parametric cytokine secretion profiles identified the surface treatment with human blood plasma as a predictive test condition. The reliability of the test condition was proofed by studies on polytetrafluorethylene (PTFE), silicone, polyethylene and titanium, finally correlating to state-of-the-art in vivo studies. This motivated our development of biomimetic 3D tissue models, resembling by a two-matrix-system, based on fibrin and collagen hydrogels, the matrix composition in a wound. After 13 days, vital macrophages adjacent to the biomaterial surface demonstrated the suitability of the biomimetic 3D models for longer contact to blood components. The soft tissue reaction after biomaterial contact was assessed by integrating fibroblasts in a 3D matrix. Multi-parametric analyses, compromising inflammatory and tissue remodeling parameters, generated a complex data matrix, finally characterizing the biomimetic 3D models. Most important, by reducing the dimensions of the data matrix, applying a principal component analysis, the reliability of the biomimetic 3D models predicted the fibrotic characteristics of the reference materials.

Biography:

Maria Lindqvist has her expertise in stem cells therapy, gene therapy, immunotherapy and proteomics. Her goal is to combine these skills in order to be able to offer personalised medicine for diseases like cancer and diabetes as well as rare diseases like myopathies. She is mostly interested in diseases that affect children.

Abstract:

Statement of the Problem: We have earlier by TUNEL staining established that overexpression of Wnt7a which is a ligand of the Vangl2 receptor increases apoptosis of Jurkat T-cells compared to control. The purpose of this study is to see how overexpression of Vangl2 affects apoptosis and inflammation.

Methods: Jurkat T-cells were cultured on coverslips in 6-well plates until they became 80% confluent. They were transfected with a commercially bought Vangl2-GFP construct for 24 or 48 hours while the controls were transfected with green fluorescent protein (GFP).

Results: The frequency of TUNEL stained cells were higher among the Jurkat T-cells that were transfected with Vangl2 compared to control cells. We could also see a rearrangement of p53 and Th17 expression which are important in inflammation.

Conclusion: We conclude that Vangl2 overexpression affects apoptosis and hypothesize that this is done via caspase-8 signaling. We also suggest that the rearrangement of p53 and Th17 expression is a result of actin translocation from the cytoplasm into the nucleus and might be mediated by exosomes.