Search results for: immune synapse

Authors: Ann Ying-An Chen, Yi-Lun Tsai, Hso-Chi Chaung

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An understanding of pathogens and the immune system has played an utmost important role in agricultural research for the development of vaccinations. The immunological synapse, cell to cell interaction play a crucial role in triggering the body's immune system, such as activation between antigen-presenting cells (APCs) and different subsets of T-cell. If these interactions are regulated appropriately, the host has the ability to defend itself against a wide spectrum of infectious pathogens. The aim of this study is to establish and to characterize a porcine immune synapse system by co-culturing T cell/APC. In this study, blood samples were collected from specific-pathogen-free piglets, and peripheral blood mononuclear cells (PBMC) were separated by using Ficoll-Pague. The PBMC were then stained with CD4 (FITC) and CD25 (PE) antibodies. Different subsets of T cells sorted by fluorescence-activated cell sorting flow cytometer were co-cultured for 24 hrs with alveolar macrophages, and the profiles of cytokine secretion and mRNA transcription levels of Toll-like receptors were examined after. Results showed that the three stages of immune synapse were clearly visible and identified under both transmission and scanning electron microscope (TEM and SEM). The significant interaction differences in toll-like receptor expressions within the co-cultured cell system were observed. The TLR7 mRNA expressions in CD4+CD25- cells were lower than those in CD4+CD25+ and CD4 -CD25+. Interestingly, the IL-10 production levels in CD4+CD25- cells (7.732 pg/mL) were significantly higher than those of CD4+CD25+ (2.636 pg/mL) and CD4 -CD25+ (2.48 pg/mL). These findings demonstrated that a clear understanding of the porcine immune synapse system can contribute greatly for further investigations on the mechanism of T-cell activation, which can benefit in the discovery of potential adjuvant candidate or effective antigen epitopes in the development of vaccinations with high efficacy.

Keywords: antigen-presenting cells, immune synapse, pig, T subsets, toll-like receptor

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Authors: Surbhi Surbhi, Andrea Erni, Gunter Meister, Harold Cremer, Christophe Beclin

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MicroRNAs (miRNAs) are short 20-23 nucleotide long non-coding RNAs; there are 2605 miRNA in humans and 1936 miRNA in mouse in total (miRBase). The nervous system expresses the most abundant miRNA and most diverse. MiRNAs play a role in many steps during neurogenesis, like cell proliferation, differentiation, neural patterning, axon pathfinding, etc. Moreover, in vitro studies suggested a role in the regulation of local translation at the synapse, thus controlling neuronal plasticity. However, due to the specific structure of miRNA molecules, an in-vivo confirmation of the general role of miRNAs in the control of neuronal plasticity is still pending. For example, their small size and their high level of sequence homology make difficult the analysis of their cellular and sub-cellular localization in-vivo by in-situ hybridization. Moreover, it was found that only 40% of the expressed miRNA molecules in a cell are included in RNA-Induced Silencing Complexes (RISC) and, therefore, involved in inhibitory interactions while the rest is silent. Definitively, the development of new tools is needed to have a better understanding of the cellular function of miRNAs, in particular their role in neuronal plasticity. Here we describe a new technique called in-vivo AGO-APP designed to investigate miRNA expression and function in-vivo. This technique is based on the expression of a small peptide derived from the human RISC-complex protein TNRC6B, called T6B, which binds all known Argonaute (Ago) proteins with high affinity allowing the efficient immunoprecipitation of AGO-bound miRNAs. We have generated two transgenic mouse lines conditionally expressing T6B either ubiquitously in the cell or targeted at the synapse. A comparison of the repertoire of miRNAs immuno-precipitated from mature neurons of both mouse lines will provide us with a list of miRNAs showing a specific activity at the synapse. The physiological role of these miRNAs will be subsequently addressed through gain and loss of function experiments.

Keywords: RNA-induced silencing complexes, TNRC6B, miRNA, argonaute, synapse, neuronal plasticity, neurogenesis

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Authors: H. Al-Khalifa, A. Al-Nasser

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The main immune organs in poultry are the thymus, spleen and bursa of Fabricius. During an immune response, mature lymphocytes and other immune cells interact with antigens in these tissues. Consequently, the mass of these organs can in some cases indicate immune status. The objective of the current study was to investigate the effect of feeding flaxseed on immune tissue weights. Cobb 500 broiler chickens were fed flaxseed at 15%, the control diet did not contain any flaxseed. Results showed that dietary supplementation with flaxseed did not affect the weights of the spleens of broiler chickens. However, it significantly lowered bursa weights (p<0.01), compared to the control diet. In addition, the bursae were thinner in appearance compared with bursii from chickens fed the control diets.

Keywords: bursa of fabricius, flaxseed, spleen, thymus

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Authors: Li Li, Li-Ru Xia, He-Ye Wang, Xiao-Dong Bi

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In this paper, we presented a highly sensitive immune-affinity monolithic array for detection of α-fetoprotein (AFP) and carcinoembryonic antigen (CEA). Firstly, the epoxy functionalized monolith arrays were fabricated using UV initiated copolymerization method. Scanning electron microscopy (SEM) image showed that the poly(BABEA-co-GMA) monolith exhibited a well-controlled skeletal and well-distributed porous structure. Then, AFP and CEA immune-affinity monolithic arrays were prepared by immobilization of AFP and CEA antibodies on epoxy functionalized monolith arrays. With a non-competitive immune response format, the presented AFP and CEA immune-affinity arrays were demonstrated as an inexpensive, flexible, homogeneous and stable array for detection of AFP and CEA.

Keywords: chemiluminescent detection, immune-affinity, monolithic copolymer array, UV-initiated copolymerization

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Authors: Dani Sukkar, Ali Kanso, Philippe Laval-Gilly, Jairo Falla-Angel

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The honeybees' immune system is challenged by different risk factors that induce various responses. However, complex scenarios where bees are exposed to different pesticides simultaneously with immune activation are not well evaluated. The Toll pathway is one of the main signaling pathways studied in invertebrate immune responses, and it is a good indicator of the effect of such complex interactions in addition to key signaling elements of other pathways like Relish of the immune deficiency (IMD) pathway or Eater, the phagocytosis receptor or vitellogenin levels. Honeybee hemocytes extracted from 5th instar larvae were exposed to imidacloprid and/or amitraz with or without the presence of the zymosan a as an immune activator. The gene expression of multiple immune related genes were studied, including spaetzle, Toll, myD88, relish, eater and vitellogenin, by real-time polymerase chain reaction after RNA extraction. The results demonstrated that the Toll pathway is mainly affected by the pesticides; imidacloprid and amitraz, especially by their different combinations. Furthermore, immune activation by zymosan A, a fungal cell-wall component, acts to mitigate to some extent the effect of pesticides on the different levels of the Toll pathway. In addition, imidacloprid, amitraz, and zymosan A have complex and context-specific interactions depending on the levels of immune activation and the pathway evaluated affecting immune-gene expression differently.

Keywords: toll pathway, immune modulation, β-glucan, imidacloprid, amitraz, honeybees, immune genes

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Authors: Mir Mohammad Reza Hosseini

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In new years immune checkpoint inhibitors have gathered care as being one of the greatest talented kinds of immunotherapy on the prospect. There has been a specific emphasis on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). In 2011, ipilimumab, the primary antibody obstructive an immune checkpoint (CTLA4) was authorized. It is now documented that recognized tumors have many devices of overpowering the antitumor immune response, counting manufacture of repressive cytokines, staffing of immunosuppressive immune cells, and upregulation of coinhibitory receptors recognized as immune checkpoints. This was fast followed by the growth of monoclonal antibodies directing PD1 (pembrolizumab and nivolumab) and PDL1 (atezolizumab and durvalumab). Anti-PD1/PDL1 antibodies have developed some of the greatest extensively set anticancer therapies. We also compare and difference their present place in cancer therapy and designs of immune-related toxicities and deliberate the role of dual immune checkpoint inhibition and plans for the organization of immune-related opposing proceedings. In this review, the employed code and present growth of numerous immune checkpoint inhibitors are abridged, while the communicating device and new development of Immune checkpoint inhibitors in cancer therapy-based synergistic therapies with additional immunotherapy, chemotherapy, phototherapy, and radiotherapy in important and clinical educations in the historical 5 years are portrayed and tinted. Lastly, we disapprovingly measure these methods and effort to find their fortes and faintness based on pre-clinical and clinical information.

Keywords: checkpoint, cancer therapy, PD-1, PDL-1, CTLA4, immunosuppressive

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Authors: Atefeh Esmailnejad, Gholamreza Nikbakht Brujeni

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Major histocompatibility complex (MHC) is one of the best characterized genetic regions associated with immune responses and controlling disease resistance in chicken. Association of the MHC with a wide range of immune responses makes it a valuable predictive factor for the disease pathogenesis and outcome. In this study, the association of MHC with cell-mediated immune responses was analyzed in commercial broiler chicken. The tandem repeat LEI0258 was applied to investigate the MHC polymorphism. Cell-mediated immune response was evaluated by peripheral blood lymphocyte proliferation assay using MTT method. Association study revealed a significant influence of MHC alleles on cellular immune responses in this population. Alleles 385 and 448 bp were associated with elevated cell-mediated immunity. Haplotypes associated with improved immune responses could be considered as candidate markers for disease resistance and applied to breeding strategies.

Keywords: MHC, cell-mediated immunity, broiler, chicken

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Authors: Wirot Likittrakulwong, Pisit Poolprasert, Tossaporn Incharoen

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Germinated paddy rice (GPR) has the potential to be used as a feed ingredient. However, their properties have not been fully investigated. This paper examined the nutrient digestibility and the relationship to immune activity in Roman hens fed with GPR. It was found that true and apparent metabolizable energy (ME) values of GPR were 3.20 and 3.28 kcal/g air dry, respectively. GPR exhibited high content of phytonutrients, especially GABA. GPR showed similar protein profiles in comparison to non-germinated paddy rice. For immune activity, the feed with GPR enhanced the immune activity of Roman hens under high stocking density stress as evidenced by the activity of superoxide dismutase (SOD) and lysozyme activity. In this study, GPR is proved to be a good source of functional ingredient for chicken feed.

Keywords: germinated paddy rice, nutrient digestibility, immune activity, functional property

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Authors: Sara Grazhdani, Alma Cili, Arben Ivanaj

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Immune Thrombocytopenic Purpura is an autoimmune disease characterized by the destruction of platelets by immune mediators, their deficient production in the red bone marrow and increased splenic sequestration, leading to the appearance of thrombocytopenia and increased risk of hemorrhage. Treatment is indicated in patients with low platelet counts (<30 x 10 9 /L) who present clinically with hemorrhagic events or are at increased risk for hemorrhage. The goal of the treatment remains (I) prevention of hemorrhagic events and deaths resulting from them, (II) reaching an adequate level of the number of platelets, (III) treatment of patients with as few toxic effects as possible. Corticosteroid therapy remains the first choice in the treatment of patients with Primary Immune Thrombocytopenic Purpura. Rituximab (Mabthera) remains the first choice in the second line in the treatment of patients with Immune Thrombocytopenic Purpura, refractory to the use of cortisones.

Keywords: ITP, rituximab, prednisolone, relapse

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Authors: Husham Bayazed

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Purpose of Presentation: The eye is one of a few sites in the body with immune privilege (IP). However, this IP is relatively easily bypassed in the face of sufficient strong local or systemic immunological responses. As immune responses are crucial elements of the repair response, the eye has developed distinct mechanisms to deliver immune responses to injury in the avascular regions of the eye. This presentation may cover and provide an overview of the mechanisms that dictate immune cell trafficking to the local ocular microenvironment in response to different autoimmune and inflammatory-mediated diseases. Recent Findings: Literature reviews declare that immune responses and inflammation play a key role in a diverse range of eye diseases. In recent years, our understanding of ocular immune responses has widely spread in ocular surface inflammation, uveitis, age-related macular degeneration (AMD), glaucoma, transplantation rejection, and other ocular diseases. It is becoming increasingly clear that multiple seemingly unrelated diseases involve immune responses with common themes in their ocular pathogenesis. Recent studies are focusing on elucidating the pathogenesis of ocular inflammatory disease to identify new targets for immunotherapy that will not only improve efficacy but also minimize adverse effects from traditional therapy. Summary: While IP was believed to protect the eye from day-to-day inflammatory insults, however, it is relatively easily breached in the face of different strong local or systemic immunological and inflammatory responses. Therefore, the ocular immune response encapsulates the full range of classical and non-classical immune responses and demonstrates many features which are reflected in other tissues, but eye tissues, by modifying these responses, may reveal unexpected and novel findings which are relevant to immune responses generally. This may have therapeutic potential for new targeting immunotherapy, restoring immune tolerance in ocular autoimmune and inflammatory diseases, and preventing rejection such as stem cells, currently being considered for treatment of worldwide blinding diseases such as AMD.

Keywords: ocular diseases, immunology, immune privilege, immunotherapy

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Authors: Yahia Massinissa, Melakhessou Med Akram, Mezahdia Mehdi, Marref Salah Eddine

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Cytokines are natural proteins which act as true intercellular communication signals in immune and inflammatory responses. Reverse signaling pathways that activate cytokines help to regulate different functions at the target cell, causing its activation, its proliferation, the differentiation, its survival or death. It was shown that malfunctioning of the cytokine regulation, particularly over-expression, contributes to the onset and development of certain serious diseases such as chronic rheumatoid arthritis, Crohn's disease, psoriasis, lupus. The action mode of Kinoid® technology is based on the principle vaccine: The patient's immune system is activated so that it neutralizes itself and the factor responsible for the disease. When applied specifically to autoimmune diseases, therapeutic vaccination allows the body to neutralize cytokines (proteins) overproduced through a highly targeted stimulation of the immune system.

Keywords: cytokines, Kinoid tech, auto-immune diseases, vaccination

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Authors: S. Gherbi, F. Bouchareb

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This paper deals with the novel intelligent bio-inspired control strategies, it presents a novel approach based on an optimal fuzzy immune PID parameters tuning, it is a combination of a PID controller, inspired by the human immune mechanism with fuzzy logic. Such controller offers more possibilities to deal with the delayed systems control difficulties due to the delay term. Indeed, we use an optimization approach to tune the four parameters of the controller in addition to the fuzzy function; the obtained controller is implemented in a modified Smith predictor structure, which is well known that it is the most efficient to the control of delayed systems. The application of the presented approach to control a three tank delay system shows good performances and proves the efficiency of the method.

Keywords: delayed systems, fuzzy immune PID, optimization, Smith predictor

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Authors: Muneeb Ahmad, Ali Raza

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A computational method inspired by the immune system (IS) is presented, leveraging its shared characteristics of robustness, fault tolerance, scalability, and adaptability with swarm intelligence. This method aims to showcase flocking behaviors in a swarm of robots (SR). The innate part of the IS offers a variety of reactive and probabilistic cell functions alongside its self-regulation mechanism which have been translated to enable swarming behaviors. Although, the research is specially focused on flocking behaviors in a variety of simulated environments using e-puck robots in a physics-based simulator (CoppeliaSim); the artificial innate immune system (AIIS) can exhibit other swarm behaviors as well. The effectiveness of the immuno-inspired approach has been established with extensive experimentations, for scalability and adaptability, using standard swarm benchmarks as well as the immunological regulatory functions (i.e., Dendritic Cells’ Maturity and Inflammation). The AIIS-based approach has proved to be a scalable and adaptive solution for emulating the flocking behavior of SR.

Keywords: artificial innate immune system, flocking swarm, immune system, swarm intelligence

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Authors: Husham Bayazed

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A growing number of studies indicate that atherosclerotic coronary artery disease (CAD) has a complex pathogenesis that extends beyond cholesterol intimal infiltration. The atherosclerosis process may involve an immune micro-environmental condition driven by local activation of the adaptive and innate immunity arrays, resulting in the formation of atherosclerotic plaques. Therefore, despite the wide usage of lipid-lowering agents, these devastating coronary diseases are not averted either at primary or secondary prevention levels. Many trials have recently shown an interest in the immune targeting of the inflammatory process of atherosclerotic plaques, with the promised improvement in atherosclerotic cardiovascular disease outcomes. This recently includes the immune-modulatory drug “Canakinumab” as an anti-interleukin-1 beta monoclonal antibody in addition to "Colchicine,” which's established as a broad-effect drug in the management of other inflammatory conditions. Recent trials and studies highlight the importance of inflammation and immune reactions in the pathogenesis of atherosclerosis and plaque formation. This provides an insight to discuss and extend the therapies from old lipid-lowering drugs (statins) to anti-inflammatory drugs (colchicine) and new targeted immune-modulatory therapies like inhibitors of IL-1 beta (canakinumab) currently under investigation.

Keywords: atherosclerotic plagues, immune microenvironment, lipid-lowering agents, and immunomodulatory drugs

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Authors: Seyong Oh, Jin-Hong Park

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Recently, neuromorphic computing based on brain-inspired artificial neural networks (ANNs) has attracted huge amount of research interests due to the technological abilities to facilitate massively parallel, low-energy consuming, and event-driven computing. In particular, research on artificial synapse that imitate biological synapses responsible for human information processing and memory is in the spotlight. Here, we demonstrate a photosynaptic device, wherein a synaptic weight is governed by a mixed spike consisting of voltage and light spikes. Compared to the device operated only by the voltage spike, ∆G in the proposed photosynaptic device significantly increased from -2.32nS to 5.95nS with no degradation of nonlinearity (NL) (potentiation/depression values were changed from 4.24/8 to 5/8). Furthermore, the Modified National Institute of Standards and Technology (MNIST) digit pattern recognition rates improved from 36% and 49% to 50% and 62% in ANNs consisting of the synaptic devices with 20 and 100 weight states, respectively. We expect that the photosynaptic device technology processed by optoelectronic spike will play an important role in implementing the neuromorphic computing systems in the future.

Keywords: optoelectronic synapse, IGZO (Indium-Gallium-Zinc Oxide) photosynaptic device, optoelectronic spiking process, neuromorphic computing

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Authors: Pei-Chann Chang, Jhen-Fu Liao, Chin-Hung Teng, Meng-Hui Chen

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This research combines artificial immune system with user and item based collaborative filtering to create an efficient and accurate recommendation system. By applying the characteristic of antibodies and antigens in the artificial immune system and using Pearson correlation coefficient as the affinity threshold to cluster the data, our collaborative filtering can effectively find useful users and items for rating prediction. This research uses MovieLens dataset as our testing target to evaluate the effectiveness of the algorithm developed in this study. The experimental results show that the algorithm can effectively and accurately predict the movie ratings. Compared to some state of the art collaborative filtering systems, our system outperforms them in terms of the mean absolute error on the MovieLens dataset.

Keywords: artificial immune system, collaborative filtering, recommendation system, similarity

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Authors: Arash Jafari, Somaye Bahrami, Mohammad Hossein Razi Jalali

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The aim of this study was the isolation and identification of excretory-secretory and somatic antigens from D. dendriticum by SDS-PAGE and evaluation of humeral immune response against these antigens. The sera of infected sheep with different infection degrees were collected. Somatic and ES proteins were isolated with SDS PAGE. Immunogenicity properties of the resulting proteins were determined using western blot analysis. The total extract of somatic antigens analysed by SDS-PAGE revealed 21 proteins. In mild infection, bands of 130 KDa were immune dominant. In moderate infections 48, 80 and 130 KDa and in heavy infections 48, 60, 80, 130 KDa were detected as immune dominant bands. In ES antigens, mild infection 130 KDa, in moderate infection 100, 120 and 130 KDa and in heavy infection 45, 80, 85, 100, 120 and 130 KDa were immune dominant bands. The most immunogenic protein band during different degrees of infection was 130KDa.

Keywords: Dicrocoelium dendriticum excretory-secretory antigens, somatic antigens, western blot

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Elham Javanroudi

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Introduction: Tuberculosis (TB) is a known disease with hidden features caused by Mycobacterium tuberculosis (MTB). This disease, which is one of the 10 deadliest in the world, has caused millions of deaths in recent decades. Furthermore, TB is responsible for infecting about 30% population of world. Like any infection, TB can activate the immune system by locating and colonization in the human body, especially in the alveoli. TB is granulomatosis, so MTB can absorb the host’s immune cells and other cells to form granuloma. Method: Different databases (e.g., PubMed) were recruited to prepare this paper and fulfill our goals to search and find effective papers and investigations. Results: Immune response to MTB is related to T cell killers and contains CD1, CD4, and CD8 T lymphocytes. CD1 lymphocytes can recognize glycolipids, which highly exist in the Mycobacterial fatty cell wall. CD4 lymphocytes and macrophages form granuloma, and it is the main line of immune response to Mycobacteria. On the other hand, CD8 cells have cytolytic function for directly killing MTB by secretion of granulysin. Other functions and secretion to the deal are interleukin-12 (IL-12) by induction of expression interferon-γ (INF-γ) for macrophages activation and creating a granuloma, and tumor necrosis factor (TNF) by promoting macrophage phagolysosomal fusion. Conclusion: Immune cells in battle with MTB are macrophages, dendritic cells (DCs), neutrophils, and natural killer (NK) cells. These immune cells can recognize the Mycobacterium by various receptors, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and C-type lectin receptors (CLRs) located in the cell surface. In human alveoli exist about 50 dendritic macrophages, which have close communication with other immune cells in the circulating system and epithelial cells to deal with Mycobacteria. Against immune cells, MTB handles some factors (e.g., cordfactor, O-Ag, lipoarabinomannan, sulfatides, and adenylate cyclase) and practical functions (e.g., inhibition of macrophages).

Keywords: mycobacterium tuberculosis, immune responses, immunological mechanisms, respiratory tuberculosis

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Authors: Florian Billing, Soren Segan, Meike Jakobi, Elsa Arefaine, Aliki Jerch, Xin Xiong, Matthias Becker, Thomas Joos, Burkhard Schlosshauer, Ulrich Rothbauer, Nicole Schneiderhan-Marra, Hanna Hartmann, Christopher Shipp

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The immune response plays a major role in implant biocompatibility, but an understanding of how to design biomaterials for specific immune responses is yet to be achieved. We aimed to better understand how changing certain material properties can drive immune responses. To this end, we tested immune response to experimental implant coatings that vary in specific characteristics. A layer-by-layer approach was employed to vary surface charge and wettability. Human-based in vitro models (THP-1 macrophages and primary peripheral blood mononuclear cells (PBMCS)) were used to assess immune responses using multiplex cytokine analysis, flow cytometry (CD molecule expression) and microscopy (cell morphology). We observed dramatic differences in immune response due to specific alterations in coating properties. For example altering the surface charge of coating A from anionic to cationic resulted in the substantial elevation of the pro-inflammatory molecules IL-1beta, IL-6, TNF-alpha and MIP-1beta, while the pro-wound healing factor VEGF was significantly down-regulated. We also observed changes in cell surface marker expression in relation to altered coating properties, such as CD16 on NK Cells and HLA-DR on monocytes. We furthermore observed changes in the morphology of THP-1 macrophages following cultivation on different coatings. A correlation between these morphological changes and the cytokine expression profile is ongoing. Targeted changes in biomaterial properties can produce vast differences in immune response. The properties of the coatings examined here may, therefore, be a method to direct specific biological responses in order to improve implant biocompatibility.

Keywords: biomaterials, coatings, immune system, implants

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Authors: Tara Miller, Tariq Ganief, Jonathan Blackburn

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Millions of babies are still born to HIV-infected mothers each year despite the ramped-up HAART use. However, these infants are HIV uninfected but exposed, which is now a growing population that has weakened immune systems and poorer outcomes. Due to HIV exposure and possible ARV exposure during pregnancy and breastfeeding, these infants are believed to have altered immune responses and microbiomes when compared to their healthy counterparts. The gut microbiome roles an important role in infant development, specifically in the immune system. Research has shown these HIV-exposed, uninfected infants have weaker immune responses to their neonate vaccines, and in developing countries, this leaves them vulnerable to opportunistic disease. By gaining a deeper understanding of the gut microbiome and the products of the microbes via metaproteomic analysis, we can hopefully understand and improve the immune system and health of these infants. To investigate the metaproteome of the infants’ guts, mass spectrometry will be used, followed by data analysis using DIA-NN. The hypothesized results are that the HIV-exposed, uninfected infants have an altered microbiome compared to their healthy counterparts. Additionally, the differences found are hypothesized to be involved with inflammation which would contribute to the poor health of the infants.

Keywords: HIV, mass spectrometry, metaproteomics, microbiome

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Authors: S. Kozlovski, S.W. Feigelson, R. Alon

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The b2 integrin ligands ICAM-1 ICAM-2 and the endothelial VLA-4 integrin ligand VCAM-1 are constitutively expressed on different lung vessels and on high endothelial venules (HEVs), the main portal for lymphocyte entry from the blood into lung draining lymph nodes. ICAMs are also ubiquitously expressed by many antigen-presenting leukocytes and have been traditionally suggested as critical for the various antigen-specific immune synapses generated by these distinct leukocytes and specific naïve and effector T cells. Loss of both ICAM-1 and ICAM-2 on the lung vasculature reduces the ability to patrol monocytes and Tregs to patrol the lung vasculature at a steady state. Our new findings suggest, however, that in terms of innate leukocyte trafficking into the lung lamina propria, both constitutively expressed and virus-induced vascular VCAM-1 can functionally compensate for the loss of these ICAMs. In a mouse model for influenza infection, neutrophil and NK cell recruitment and clearance of influenza remained normal in mice deficient in both ICAMs. Strikingly, mice deficient in both ICAMs also mounted normal influenza-specific CD8 proliferation and differentiation. In addition, these mice normally combated secondary influenza infection, indicating that the presence of ICAMs on conventional dendritic cells (cDCs) that present viral antigens are not required for immune synapse formation between these APCs and naïve CD8 T cells as previously suggested. Furthermore, long-lasting humoral responses critical for protection from a secondary homosubtypic influenza infection were also normal in mice deficient in both ICAM-1 and ICAM-2. Collectively, our results suggest that the expression of ICAM-1 and ICAM-2 on lung endothelial and epithelial cells, as well as on DCs and B cells, is not critical for the generation of innate or adaptive anti-viral immunity in the lungs. Our findings also suggest that endothelial VCAM-1 can substitute for the functions of vascular ICAMs in leukocyte trafficking into various lung compartments.

Keywords: emigration, ICAM-1, lymph nodes, VCAM-1

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Authors: Yi-Lin Chen, Sheng-Jou Hung, Tsunglin Liu

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Adaptive immune system recognizes a wide range of antigens via expressing a large number of structurally distinct T cell and B cell receptor genes. The distinct receptor genes arise from complex rearrangements called V(D)J recombination, and constitute the immune repertoire. A common method of profiling immune repertoire is via amplifying recombined receptor genes using multiple primers and high-throughput sequencing. This multiplex-PCR approach is efficient; however, the resulting repertoire can be distorted because of primer bias. To eliminate primer bias, 5’ RACE is an alternative amplification approach. However, the application of RACE approach is limited by its low efficiency (i.e., the majority of data are non-regular receptor sequences, e.g., containing intronic segments) and lack of the convenient tool for analysis. We propose a computational tool that can correctly identify non-regular receptor sequences in RACE data via aligning receptor sequences against the whole gene instead of only the exon regions as done in all other tools. Using our tool, the remaining regular data allow for an accurate profiling of immune repertoire. In addition, a RACE approach is improved to yield a higher fraction of regular T-cell receptor sequences. Finally, we quantify the degree of primer bias of a multiplex-PCR approach via comparing it to the RACE approach. The results reveal significant differences in frequency of VJ combination by the two approaches. Together, we provide a new experimental and computation pipeline for an unbiased profiling of immune repertoire. As immune repertoire profiling has many applications, e.g., tracing bacterial and viral infection, detection of T cell lymphoma and minimal residual disease, monitoring cancer immunotherapy, etc., our work should benefit scientists who are interested in the applications.

Keywords: immune repertoire, T-cell receptor, 5' RACE, high-throughput sequencing, sequence alignment

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Authors: Adineh Tajmousavilangerudi, Ali Zein Alabiden Tlais, Raffaella Di Cagno

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The SARS-Cov-2 pandemic has exposed our vulnerability to new illnesses and novel viruses that attack our immune systems, particularly in the elderly. The vaccine is being gradually introduced over the world, but new strains of the virus and COVID-19 will emerge and continue to cause illness. Aging is associated with significant changes in intestinal physiology, which increases the production of inflammatory products, alters the gut microbiota, and consequently establish inadequate immune response to minimize symptoms and disease development. In this context, older people who followed a Mediterranean-style diet, rich in polyphenols and dietary fiber, performed better physically and mentally (1,2). This demonstrates the importance of the human gut microbiome in transforming complex dietary macromolecules into the most biologically available and active nutrients, which in turn help to regulate metabolism and both intestinal and systemic immune function (3,4). The role of lactic acid fermentation is prominent also as a powerful tool for improving the nutritional quality of the human diet by releasing nutrients and boosting the complex bioactive compounds and vitamin content. the PhD project aims to design fermented and functional foods/beverages capable of modulating human immune function via the gut microbiome.

Keywords: functional bevarage, fermented beverage, gut microbiota functionality, immun system

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Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

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Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

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Authors: Stephanie Newman

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Niemann-Pick Type C disease is a rare, usually fatal lysosomal storage disorder. Although clinically characterized by progressive neurodegeneration, there is also evidence of altered innate immune responses such as neuroinflammation that promote disease progression. We have initiated an investigation into whether phagocytosis, an important innate immune activity and the process by which particles are ingested is defective in NPC. Using an in vitro assay, we have shown that NPC macrophages have a deficiency in the phagocytosis of different particles. We plan to investigate the mechanistic basis for impaired phagocytosis, the contribution that this deficiency makes to disease pathology, and whether therapies that have shown in vivo benefit are able to restore phagocytic activity.

Keywords: Niemann Pick Disease C, phagocytosis, innate immunity, lysosomal storage disorder

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Authors: Jiraporn Rojtinnakorn, Mallika Supa-Aksorn, Sudaporn Tongsiri, Prachaub Chaibu

Abstract:

Marble goby is one of high demand consuming in Southeast Asia. However, the product was from riparian fisheries because of low yield in aquaculture, especially in nursery stage. Therefore, we studied for herb supplement in pellet feed of marble goby fingering. Garlic, a common herb and illustrated novel pharmaceutical and medical effectiveness, was considered. Garlic extracts with water (DW), 50% EtOH (50E), 95% EtOH (95E) and diethyl ether (DE) were subjected for feed additive to induce immune response in marble goby fingering for 0 (control), 0.3, 0.5, 1.0, 3.0 and 5.0 % (w/w). After seven days of feeding, blood was collected for analysis of blood composition; i.e. haematocrit (HCT), red blood cells (RBC), white blood cells (WBC) and humoral immune responses; i.e. lysozyme activity (Lys). It was resulted that values of HCT, WBC and Lys in all garlic fed group were significantly different from control (p < 0.05). For HCT, the highest values belonged to 5% DW and 0.5% 95E. For WBC and Lys, the highest values were 5% DW. For RBC, there was not obviously significant (p < 0.05). There were only 3 groups; 0.5% 95E, 1% and 5% DW, showed distinct statistical significance from the other groups. It was concluded that garlic extracts showed satisfy bioactivity to enhancing innate immune response in marble goby fingering. This result will be valuable for specific feed formula of marble goby nursery.

Keywords: garlic extract, innate immune, marble goby, Oxyeleotris marmoratus

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Authors: S. Subramaniam, J. S. A. Rao, P. Ramdas, K. R. Selvaduray, N. M. Han, M. K. Kutty, A. K. Radhakrishnan

Abstract:

Immune system is a complex system where the immune cells have the capability to respond against a wide range of immune challenges including cancer progression. However, in the event of cancer development, tumour cells trigger immunosuppressive environment via activation of myeloid-derived suppressor cells and T regulatory (Treg) cells. The Treg cells are subset of CD4+ T lymphocytes, known to have crucial roles in regulating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Dysregulation of these mechanisms could lead to cancer progression and immune suppression. Recently, there are many studies reporting on the effects of natural bioactive compounds on immune responses against cancer. It was known that tocotrienol-rich-fraction consisting 70% tocotrienols and 30% α-tocopherol is able to exhibit immunomodulatory as well as anti-cancer properties. Hence, this study was designed to evaluate the effects of gamma-tocotrienol (G-T3) supplementation on T-reg cells in a syngeneic mouse model of breast cancer. In this study, female BALB/c mice were divided into two groups and fed with either soy oil (vehicle) or gamma-tocotrienol (G-T3) for two weeks followed by inoculation with tumour cells. All the mice continued to receive the same supplementation until day 49. The results showed a significant reduction in tumour volume and weight in G-T3 fed mice compared to vehicle-fed mice. Lung and liver histology showed reduced evidence of metastasis in tumour-bearing G-T3 fed mice. Besides that, flow cytometry analysis revealed T-helper cell population was increased, and T-regulatory cell population was suppressed following G-T3 supplementation. Moreover, immunohistochemistry analysis showed that there was a marked decrease in the expression of FOXP3 in the G-T3 fed tumour bearing mice. In conclusion, the G-T3 supplementation showed good prognosis towards breast cancer by enhancing the immune response in tumour-bearing mice. Therefore, gamma-T3 can be used as immunotherapy agent for the treatment of breast cancer.

Keywords: breast cancer, gamma tocotrienol, immune suppression, supplement

Procedia PDF Downloads 181

Authors: Cliff Shunsheng Han

Abstract:

Identifying the direct allergy cause that can be easily mitigated is the foundation to stop the allergy epidemic that has been started in the seventies. It has confirmed that the personal and social hygiene practices are associated with the allergy prevalence. But direct causes have been found, and proposed translational measures have not been effective. This study, assisted by a particular case of allergies, has seen the direct cause of allergies, developed a valid test resulted in lasting relief for allergies, and constructed theory describing general relationship between microbiota and host immune system. Saliva samples were collected from a subject for three years during which time the person experienced yearlong allergy, seasonal allergy, and remission of allergy symptoms. Bacterial DNA was extracted and 16S rRNA genes were profiled with Illumina sequencing technology. The analyzing results indicate that the possible direct cause of allergy is the lacking probiotic bacteria in the oral cavity, such as genera Streptococcus and Veilonella, that can produce metabolites to pacify immune system. Targeted promotion of those bacteria with a compound designed for them, has led to lasting remissions of allergic rhinitis. During the development of the translational measure, the subject's oral biofilm was completely destructed by a moderate fever due to an unrelated respiratory infection. The incident not only facilitated the development of the heat based microbiota reseeding procedure but also indicated a possible natural switch that subsequently increases the efficacy of the immune system previously restrained by metabolites from microbiota. These results lead to the proposal of a Theory of Negative Trigger (TNT) to describe the relationship between oral probiotics and immune system, in which probiotics are the negative trigger that will release the power of immune system when removed by fever or modern lifestyles. This study could open doors leading to further understanding of how the immune system functions under the influence of microbiota as well as validate simple traditional practices for healthy living.

Keywords: oral microbiome, allergy, immune system, infection

Procedia PDF Downloads 98

Authors: Vinod Kumar Tewari, Mazhar Husain, Hari Kishan Das Gupta

Abstract:

Background: Primary or secondary brain death is also accompanied with vasospasm of the perforators other than tissue disruption & further exaggerates the anoxic damage, in the form of neuropraxia. In normal conditions the excitatory impulse propagates as anterograde neurotransmission (ANT) and at the level of synapse, glutamate activates NMDA receptors on postsynaptic membrane. Nitric oxide (NO) is produced by Nitric oxide Synthetase (NOS) in postsynaptic dendride or cell body and travels backwards across a chemical synapse to bind to the axon terminal of a presynaptic neuron for regulation of ANT this process is called as the retrograde neurotransmission (RNT). Thus the primary function of NO is RNT and the purpose of RNT is regulation of chemical neurotransmission at synapse. For this reason, RNT allows neural circuits to create feedback loops. The haem is the ligand binding site of NO receptor (sGC) at presynaptic membrane. The affinity of haem exhibits > 10,000-fold excess for NO than Oxygen (THE 10,000 FOLD EFFECT). In pathological conditions ANT, normal synaptic activity including RNT is absent. NO donors like sodium nitroprusside (SNP) releases NO by activating NOS at the level of postsynaptic area. NO now travels backwards across a chemical synapse to bind to the haem of NO receptor at axon terminal of a presynaptic neuron as in normal condition. NO now acts as impulse generator (at presynaptic membrane) thus bypasses the normal ANT. Also the arteriolar perforators are having Nitric Oxide Synthetase (NOS) at the adventitial side (outer border) on which sodium nitroprusside (SNP) acts; causing release of Nitric Oxide (NO) which vasodilates the perforators causing gush of blood in brain’s tissue and reversal of brain death. Objective: In brain death cases we only think for various transplantations but this study being a pilot study reverses some criteria of brain death by vasodilating the arteriolar perforators. To study the effect of intrathecal sodium nitroprusside (IT SNP) in cases of brain death in which: 1. Retrograde transmission = assessed by the hyperacute timings of reversal 2. The arteriolar perforator vasodilatation caused by NO and the maintenance of reversal of brain death reversal. Methods: 35 year old male, who became brain death after head injury and has not shown any signs of improvement after every maneuver for 6 hours, a single superfusion done by SNP via transoptic canal route for quadrigeminal cistern and cisternal puncture for IV ventricular with SNP done. Results: He showed spontaneous respiration (7 bouts) with TCD studies showing start of pulsations of various branches of common carotid arteries. Conclusions: In future we can give this SNP via transoptic canal route and in IV ventricle before declaring the body to be utilized for transplantations or dead or in broader way we can say that in near future it is possible to revert back from brain death or we have to modify our criterion.

Keywords: brain death, intrathecal sodium nitroprusside, TCD studies, perforators, vasodilatations, retrograde transmission, 10, 000 fold effect

Procedia PDF Downloads 368

Authors: Samul Sahile Kebede

Abstract:

Back ground: -Immune hemolytic anemia commonly affects human immune deficiency, infected individuals. Among anemic HIV patients in Africa, the burden of IHA due to autoantibody was ranged from 2.34 to 3.06 due to the drug was 43.4%. IHA due to autoimmune is potentially a fatal complication of HIV, which accompanies the greatest percent from acquired hemolytic anemia. Objective: -The main aim of this study was to determine the magnitude and associated factors of immune hemolytic anemia among human immuno deficiency virus infected adults at the university of Gondar comprehensive specialized hospital north west Ethiopia from March to April 2021. Methods: - An institution-based cross-sectional study was conducted on 358 human immunodeficiency virus-infected adults selected by systematic random sampling at the University of Gondar comprehensive specialized hospital from March to April 2021. Data for socio-demography, dietary and clinical data were collected by structured pretested questionnaire. Five ml of venous blood was drawn from each participant and analyzed by Unicel DHX 800 hematology analyzer, blood film examination, and antihuman globulin test were performed to the diagnosis of immune hemolytic anemia. Data was entered into Epidata version 4.6 and analyzed by STATA version 14. Descriptive statistics were computed and firth penalized logistic regression was used to identify predictors. P value less than 0.005 interpreted as significant. Result; - The overall prevalence of immune hemolytic anemia was 2.8 % (10 of 358 participants). Of these, 5 were males, and 7 were in the 31 to 50 year age group. Among individuals with immune hemolytic anemia, 40 % mild and 60 % moderate anemia. The factors that showed association were family history of anemia (AOR 8.30 at 95% CI 1.56, 44.12), not eating meat (AOR 7.39 at 95% CI 1.25, 45.0), and high viral load 6.94 at 95% CI (1.13, 42.6). Conclusion and recommendation; Immune hemolytic anemia is less frequent condition in human immunodeficiency virus infected adults, and moderate anemia was common in this population. The prevalence was increased with a high viral load, a family history of anemia, and not eating meat. In these patients, early detection and treatment of immune hemolytic anemia is necessary.

Keywords: anemia, hemolytic, immune, auto immune, HIV/AIDS

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