Abstract 293: Cardiac Arrest and Resuscitation Causes Immunodeficiency That Involves the Hypothalamic-Pituitary-Adrenal Axis

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Yuntian Shen ◽  
Qiang Zhao ◽  
Jiangbo Wu ◽  
Zhuoran Wang ◽  
Wei Yang
Keyword(s):  
Immune Response ◽  
Cardiac Arrest ◽  
Immune System ◽  
Hpa Axis ◽  
Time Course ◽  
Immune Cell ◽  
Infectious Complications ◽  
Hypothalamic Pituitary Adrenal ◽  
Immune Organs ◽  
High Incidence

Introduction: Cardiac arrest (CA) is associated with high mortality and morbidity, which is in part due to infectious complications developed in CA patients. Infection complications, particularly pneumonia, occur in approximately 60% of CA patients. Given this high incidence, we hypothesized that after CA, the immune system is impaired, which increases the susceptibility of CA patients to potential infections. Therefore, in this study, we systematically examined the immune response in the brain and peripheral immune organs after CA. Methods: Mice were subjected to CA and cardiopulmonary resuscitation (CA/CPR). Flow cytometry, ELISA, immunohistochemistry, and quantitative PCR were used to analyze the immune response in various post-CA organs. Results: First, we characterized the time course of the immune response in the spleen after CA/CPR. CA/CPR induced significant changes in all major immune cell populations. Notably, B cell frequencies decreased, while T cell frequencies increased, in various organs on day 3 post-CA. Further, the levels of pro-inflammatory cytokines, eg IL-6, were markedly increased in the blood and brain after CA. Critically, we found that the lymphocyte counts in the spleen and thymus were dramatically lower in CA mice than in sham mice. Interestingly, CA/CPR caused progressive atrophy of the spleen and thymus. Since it has been shown that CA/CPR alters activity of the hypothalamic-pituitary-adrenal (HPA) axis, we speculated that CA-induced atrophy of lymphoid organs is mediated by the HPA axis. Thus, we treated CA mice with RU486, a glucocorticoid receptor antagonist. Indeed, this treatment reversed CA-induced organ atrophy and mitigated immune cell depletion, both in the thymus and spleen. Conclusions: We provided for the first time evidence that CA/CPR rapidly induced a systemic inflammatory response followed by impairment of the immune system, which eventually led to a massive loss of immune cells in the peripheral immune organs. This CA-induced immunodeficiency appears to be mediated by dysregulation of the HPA axis. Our findings here may be of high clinical significance, considering the high incidence of infectious complications in CA patients and their detrimental effects on CA outcome.

scholarly journals Lifting the innate immune barriers to antitumor immunity

2020 ◽  
Vol 8 (1) ◽  
pp. e000695 ◽  
Author(s):  
Carla V Rothlin ◽  
Sourav Ghosh
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Immune System ◽  
T Cell ◽  
Time Course ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Cell Activity ◽  
Innate Immune ◽  
Cell Functions

The immune system evolved for adequate surveillance and killing of pathogens while minimizing host damage, such as due to chronic or exaggerated inflammation and autoimmunity. This is achieved by negative regulators and checkpoints that limit the magnitude and time course of the immune response. Tumor cells often escape immune surveillance and killing. Therefore, disrupting the brakes built into the immune system should effectively boost the anticancer immune response. The success of anti-CTLA4, anti-PD-1 and anti-PD-L1 have firmly established this proof of concept. Since the response rate of anti-CTLA4, anti-PD-1 and anti-PD-L1 is still limited, there is an intense effort for the identification of new targets and development of approaches that can expand the benefits of immunotherapy to a larger patient pool. Additional T cell checkpoints are obvious targets; however, here we focus on the unusual suspects—cells that function to initiate and guide T cell activity. Innate immunity is both an obligate prerequisite for the initiation of adaptive immune responses and a requirement for the recruitment of activated T cells to the site of action. We discuss some of the molecules present in innate immune cells, including natural killer cells, dendritic cells, macrophages, myeloid-derived suppressor cells, endothelial cells and stromal cells, that can activate or enhance innate immune cell functions, and more importantly, the inhibitors or checkpoints present in these cells that restrain their functions. Boosting innate immunity, either by enhancing activator functions or, preferably, by blocking the inhibitors, may represent a new anticancer treatment modality or at least function as adjuvants to T cell checkpoint inhibitors.

scholarly journals Influence of immunological nutrition on treatment of patients with oncological profile

2018 ◽  
Vol 1 (1) ◽  
pp. 19-24
Author(s):  
M. O. Katrichenko ◽  
I. I. Lisnyi
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Clinical Studies ◽  
Animal Studies ◽  
Immune Cell ◽  
Laboratory Data ◽  
Vital Role ◽  
Biologically Active ◽  
Protective Effects ◽  
Immunological Reactions

In the reviewed article, we consider epidemiological and laboratory data that confirm the protective effects of biologically active nutrients in our diet for various diseases. Along with various factors such as alcohol, smoking, nutrition plays a vital role in influencing the patient’s immune response by transforming cells or by preventing, or acceleration of malignancy. Many data suggest that immunoactive nutrients control inflammatory and precancerous reactions in immune cells. Immunoprophylaxis is usually associated with modulation of the immune response when inflamed, thereby improving clinical outcomes. Different nutrients, including glutamine, arginine, vitamins, minerals and long-chain fatty acids, are important components of immunological nutrition. Clinical studies associated with these substances show different results with minimal effect. However, some studies have shown that these nutrients may have immunomodulatory effects that can reduce the risk of developing cancer. Pre-clinical studies claim that most of these nutrients have a positive effect in the complex treatment of cancer patients. In this article, we will consider the effect of the above nutrients on the immune system in patients of oncologic profile. Recent evidences suggest that immunological nutrition plays an important role in the development of cancer and its progression. Data from animal studies have clearly shown that the use of immunomodulatory nutrients isolated from food, by launching a cascade of immunological reactions, can detect and eliminate the tumor. Although the technology has evolved to such an extent that we can study each individual cytokine or function of the immune cell, it is difficult to demonstrate the powerful role of the immune system in preventing or treating cancer due to the complexity of the tumor cell or heterogeneity in different patients' populations. However, the study sheds light on interactions in immune responses and cancer development, prevention and therapeutic strategies that involve modulation through biologically active agents.

scholarly journals Insights into Innate Immune Response Against SARS-CoV-2 Infection

2021 ◽  
Vol 29 (3) ◽  
pp. 255-269
Author(s):  
Adina Huțanu ◽  
Anca Meda Georgescu ◽  
Akos Vince Andrejkovits ◽  
William Au ◽  
Minodora Dobreanu
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Innate Immune System ◽  
Time Course ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Response ◽  
Humoral Factors ◽  
Key Steps

Abstract The innate immune system is mandatory for the activation of antiviral host defense and eradication of the infection. In this regard, dendritic cells, natural killer cells, macrophages, neutrophils representing the cellular component, and cytokines, interferons, complement or Toll-Like Receptors, representing the mediators of unspecific response act together for both activation of the adaptive immune response and viral clearance. Of great importance is the proper functioning of the innate immune response from the very beginning. For instance, in the early stages of viral infection, the defective interferon response leads to uncontrolled viral replication and pathogen evasion, while hypersecretion during the later stages of infection generates hyperinflammation. This cascade activation of systemic inflammation culminates with cytokine storm syndrome and hypercoagulability state, due to a close interconnection between them. Thus an unbalanced reaction, either under- or over- stimulation of the innate immune system will lead to an uncoordinated response and unfavorable disease outcomes. Since both cellular and humoral factors are involved in the time-course of the innate immune response, in this review we aimed to address their gradual involvement in the antiviral response with emphasis on key steps in SARS-CoV-2 infection.

scholarly journals Identification of Genetic Determinants of Pancreatic Cancer Immune Phenotypes by Integrative Genome-scale Analysis

2021 ◽  
Author(s):  
Yuhang Ling ◽  
Jiaqi Xu ◽  
Xuedong Wang ◽  
Jie Song ◽  
Qiuhui Qian ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Response ◽  
Dna Damage ◽  
Immune System ◽  
Immune Cell ◽  
Dna Damage Repair ◽  
Cell Interactions ◽  
Tumor Microenvironments ◽  
Damage Repair ◽  
Immune Phenotypes

Abstract Background Pancreatic cancer (PC) is a malignant neoplasm of the digestive tract that is highly malignant and difficult to diagnose at an early stage with high postoperative mortality and low cure rates. Cancer immunotherapy is innovating the clinical treatment of several cancers, but has a limited role in PC. The incomplete understanding of immune response hinders the development of gene therapy. To fill this gap, it is very necessary to classify the immunogenic subtypes of PC to understand the relationship between tumor microenvironments and clinical pathological characteristics, DNA damage repair and tumor immune response.Methods We extracted copy number change, somatic mutation and expression data from tumor genome map (TCGA). Using RNA sequencing data, we defined three different immunophenotypes and elucidated how immune cell interactions in immune subtypes vary with the background of the immune system. Further correlation analysis between DNA damage repair (DDR) related genes expression and immune response was conducted to explore the effects of DDR expression on antitumor activity in the tumor microenvironments.Results We defined three different immunophenotypes and elucidated how immune cell interactions in immune subtypes vary with the background of the immune system. When the total number of mutations was standardized, no enrichment of new epitopes was detected in immunocompetent phenotypes. These observations suggest that mutations in Th-1 enriched IS3 tumors are essentially no more immunogenic than those in IS2 cancers. We also found that the expression patterns of key IFN mediators STAT1 and / or STAT3 were increased in tumors with DDR mutations (19 of ATM, ERCC1, Rb1, BRCA2, pole and TP53), which is a reflex activation of IFN pathway.Conclusions Three defined immune subtypes show different characteristics of immune cell infiltration, revealing different manifestations in anti-cancer immune function. That is to say, clinical biological events of differential tumors are associated to immune-phenotypes. The invasive phenotype was driven by somatic mutations across immune subtypes, and DDR defect may also influence the response of tumor immune subtypes. Our results suggested that the occurrence of pancreatic cancer is related to genetic factors of immunophenotype, providing information for clinical prognosis and outcome of pancreatic cancer.

scholarly journals TrackSOM: mapping immune response dynamics through sequential clustering of time- and disease-course single-cell cytometry data

2021 ◽  
Author(s):  
Givanna Haryono Putri ◽  
Jonathan Chung ◽  
Davis N Edwards ◽  
Felix Marsh-Wakefield ◽  
Suat Dervish ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
West Nile Virus ◽  
Immune Cells ◽  
Immune Cell ◽  
West Nile Virus Infection ◽  
Cell Populations ◽  
Disease Course ◽  
Response Dynamics ◽  
Over Time

Mapping the dynamics of immune cell populations over time or disease-course is key to understanding immunopathogenesis and devising putative interventions. We present TrackSOM, an algorithm which delineates cellular populations and tracks their development over a time- or disease-course of cytometry datasets. We demonstrate TrackSOM-enabled elucidation of the immune response to West Nile Virus infection in mice, uncovering heterogeneous sub-populations of immune cells and relating their functional evolution to disease severity. TrackSOM is easy to use, encompasses few parameters, is quick to execute, and enables an integrative and dynamic overview of the immune system kinetics that underlie disease progression and/or resolution.

scholarly journals Immune gene expression profiles in high-grade urothelial carcinoma of the bladder: a NanoString study

2020 ◽  
Vol 74 (1) ◽  
pp. 53-57 ◽  
Author(s):  
Ekaterina Olkhov-Mitsel ◽  
Anjelica Hodgson ◽  
Stanley K Liu ◽  
Danny Vesprini ◽  
Jane Bayani ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Evasion ◽  
Messenger Rna ◽  
Immune Cell ◽  
Expression Profiles ◽  
Differentially Expressed Gene ◽  
Immune Gene ◽  
High Grade ◽  
Predictive Values

AimsThe advent of immune checkpoint inhibitor therapy has proven beneficial in a subset of high-grade urothelial carcinomas (HGUC) of the bladder. Although treatment selection is currently largely determined by programmed death-ligand 1 (PD-L1) status, multiple factors in the immune system may modulate the host immune response to HGUC and immunotherapy. In this pilot study, we used a transcriptomic approach to identify the immune milieu associated with PD-L1 expression to enhance our understanding of the HGUC immune evasion network.MethodsThe immune transcriptome of 40 HGUC cystectomy cases was profiled using the NanoString nCounter Human V.1.1 PanCancer Panel. All cases were assessed for associated PD-L1 status (SP263) using whole tissue sections. PD-L1 status was determined as high or low using 25% tumour and/or immune cell staining.ResultsThe most significantly differentially expressed gene was PD-L1 messenger RNA (CD274), which strongly correlated with protein expression (r=0.720, p<0.001). The sensitivity, specificity, positive and negative predictive values of CD274 for PD-L1 expression were 85%, 96%, 92% and 93%, respectively. The PD-L1 associated gene signature also included complement components C1QA and CD46 and NOD2 (innate immune system), proinflammatory cytokines CXCL14, CXCL16, CCL3, CCL3L1 and OSM along with the immune response mediator SMAD3, among others. Pathway analysis determined enrichment of these genes in interleukin-10 production, lymphocyte chemotaxis and aberrant IFNγ, NF-κB and ERK signalling networks.ConclusionsWe report key genes and pathways in the immune transcriptome and their association with PD-L1 status, which may be involved in immune evasion of HGUC and warrants further investigation.

scholarly journals Cardiac Arrest/Cardiopulmonary Resuscitation Augments Cell-Mediated Immune Function and Transiently Suppresses Humoral Immune Function

2005 ◽  
Vol 25 (11) ◽  
pp. 1424-1432 ◽  
Author(s):  
Gretchen N Neigh ◽  
Erica R Glasper ◽  
Staci D Bilbo ◽  
Richard J Traystman ◽  
A Courtney DeVries
Keyword(s):  
Cardiac Arrest ◽  
Immune System ◽  
Cardiopulmonary Resuscitation ◽  
Immune Function ◽  
Hpa Axis ◽  
Immune Activation ◽  
Neuronal Damage ◽  
Global Ischemia ◽  
Antigenic Challenge ◽  
Humoral Immune

Immune system activation has implications for cerebrovascular health, but little is known about the function of the immune system after a major cerebrovascular event, such as cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Cardiac arrest and cardiopulmonary resuscitation damages the hippocampus, an important component of the hypothalamic—pituitary—adrenal (HPA) axis, and alterations in HPA axis activity can affect immune function. We tested the hypothesis that CA/CPR (approximately 8mins) would cause HPA axis dysregulation and alter the delayed type hypersensitivity (DTH) response to antigenic challenge. We also assessed the primary and secondary antibody response of mice exposed to CA/CPR. Of the mice exposed to CA/CPR, half had brains protected by hypothermia to isolate the effects of the CA/CPR procedure from the effects of CA/CPR-induced neuronal damage. Cardiac arrest and cardiopulmonary resuscitation-induced neuronal damage resulted in a persistent elevation of blood corticosterone concentration and a concomitant augmentation of the DTH response to antigenic challenge. Furthermore, immune activation before CA/CPR decreased survival after global ischemia. These data highlight the potential impact of neuronal damage on cell-mediated immune function and the role of humoral immune activation in outcome after global ischemia.

scholarly journals Natural Compounds of Marine Origin as Inducers of Immunogenic Cell Death (ICD): Potential Role for Cancer Interception and Therapy

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 231
Author(s):  
Clementina Sansone ◽  
Antonino Bruno ◽  
Concetta Piscitelli ◽  
Denisa Baci ◽  
Angelo Fontana ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Immune System ◽  
Immune Cell ◽  
Cytotoxic T Cells ◽  
Immunogenic Cell Death ◽  
Type I ◽  
Bioactive Natural Products ◽  
Signalling Molecules ◽  
Major Factors

Regulated cell death (RCD) has always been considered a tolerogenic event. Immunogenic cell death (ICD) occurs as a consequence of tumour cell death accompanied by the release of damage-associated molecular patterns (DAMPs), triggering an immune response. ICD plays a major role in stimulating the function of the immune system in cancer during chemotherapy and radiotherapy. ICD can therefore represent one of the routes to boost anticancer immune responses. According to the recommendations of the Nomenclature Committee on Cell Death (2018), apoptosis (type I cell death) and necrosis (type II cell death) represent are not the only types of RCD, which also includes necroptosis, pyroptosis, ferroptosis and others. Specific downstream signalling molecules and death-inducing stimuli can regulate distinct forms of ICD, which develop and promote the immune cell response. Dying cells deliver different potential immunogenic signals, such as DAMPs, which are able to stimulate the immune system. The acute exposure of DAMPs can prime antitumour immunity by inducing activation of antigen-presenting cells (APC), such as dendritic cells (DC), leading to the downstream response by cytotoxic T cells and natural killer cells (NK). As ICD represents an important target to direct and develop new pharmacological interventions, the identification of bioactive natural products, which are endowed with low side effects, higher tolerability and preferentially inducing immunogenic programmed cell death, represents a priority in biomedical research. The ability of ICD to drive the immune response depends on two major factors, neither of which is intrinsic to cell death: ‘Antigenicity and adjuvanticity’. Indeed, the use of natural ICD-triggering molecules, alone or in combination with different (immuno)therapies, can result in higher efficacy and tolerability. Here, we focused on natural (marine) compounds, particularly on marine microalgae derived molecules such as exopolysaccharides, sulphated polysaccharides, glycopeptides, glycolipids, phospholipids, that are endowed with ICD-inducing properties and sulfavants. Here, we discuss novel and repurposed small-molecule ICD triggers, as well as their ability to target important molecular pathways including the IL-6, TNF-α and interferons (IFNs), leading to immune stimulation, which could be used alone or in combinatorial immunotherapeutic strategies in cancer prevention and therapies.

scholarly journals Immune Response to the Pathogenesis of COVID-19 Infection: Possible Mechanism of Nutrition (Vitamins, Supplement) and Exercise

2021 ◽  
Author(s):  
Abdullahi Alausa ◽  
Rofiat Adeyemi ◽  
Barakat Olaleke ◽  
Aminat Ismail ◽  
Faith Sunday Oyelere
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Immune Dysfunction ◽  
Nutritional Intake ◽  
Moderate Exercise ◽  
The World ◽  
Positive Results

COVID-19 infection, a ravaging disease attributed to a SARS-CoV-like illness, has brought the world to its knee, causing a pandemic, with human-human transmission as a major source of the spread of this ailment. Alarmingly, this infection based on clinical manifestations is diagnosed as virus-induced pneumonia, with over 5 million cases with a mortality rate of about 7% (based on the recently published global report). However, most deaths have been associated with patients with underlying immune dysfunction or a compromised immunesystem. As no specific therapeutics and vaccines have been reported, the strengthening of the immune system through nutritional intake and exercise is essential. Also, previous studies have documented the immune-activating capabilities of Vitamin A and D, along with supplementary induction, yielding positive results in combating previous viral challenges. Typically, the gradual upsurge of T-lymphocytes and immune cell activities has been implemented by moderate exercise activities. This review examines the role of nutrition and exercise in immune system enhancement and proposes the possible mechanism of nutrition and exercise in combating COVID-19 infection.

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