scholarly journals Distinct immune responses in patients infected with influenza or SARS-CoV-2, and in COVID-19 survivors, characterised by transcriptomic and cellular abundance differences in blood.

2021 ◽  
Author(s):  
Jelmer Legebeke ◽  
Jenny Lord ◽  
Rebekah Penrice-Randal ◽  
Andres F Vallejo ◽  
Stephen Poole ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell Activation ◽  
Cell Activation ◽  
Topological Analysis ◽  
Adaptive Immune Response ◽  
Influenza Virus Infection ◽  
The Body ◽  
Nucleosome Assembly ◽  
Bioinformatic Tools ◽  
Adaptive Immune

Background The worldwide pandemic caused by SARS-CoV-2 has claimed millions of lives and has had a profound effect on global life. Understanding the pathogenicity of the virus and the body′s response to infection is crucial in improving patient management, prognosis, and therapeutic strategies. To address this, we performed functional transcriptomic profiling to better understand the generic and specific effects of SARS-CoV-2 infection. Methods Whole blood RNA sequencing was used to profile a well characterised cohort of patients hospitalised with COVID-19, during the first wave of the pandemic prior to the availability of approved COVID-19 treatments and who went on to survive or die of COVID-19, and patients hospitalised with influenza virus infection between 2017 and 2019. Clinical parameters between patient groups were compared, and several bioinformatic tools were used to assess differences in transcript abundances and cellular composition. Results The analyses revealed contrasting innate and adaptive immune programmes, with transcripts and cell subsets associated with the innate immune response elevated in patients with influenza, and those involved in the adaptive immune response elevated in patients with COVID-19. Topological analysis identified additional gene signatures that differentiated patients with COVID-19 from patients with influenza, including insulin resistance, mitochondrial oxidative stress and interferon signalling. An efficient adaptive immune response was furthermore associated with patient survival, while an inflammatory response predicted death in patients with COVID-19. A potential prognostic signature was found based on a selection of transcript abundances, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, in the blood transcriptome of COVID-19 patients, upon admission to hospital, which can be used to stratify patients likely to survive or die. Conclusions The results identified distinct immunological signatures between SARS-CoV-2 and influenza, prognostic of disease progression and indicative of different targeted therapies. The altered transcript abundances associated with COVID-19 survivors can be used to predict more severe outcomes in patients with COVID-19.

scholarly journals Passively transferred IgG enhances humoral immunity to a red blood cell alloantigen in mice

2020 ◽  
Vol 4 (7) ◽  
pp. 1526-1537
Author(s):  
David R. Gruber ◽  
Amanda L. Richards ◽  
Heather L. Howie ◽  
Ariel M. Hay ◽  
Jenna N. Lebedev ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
T Cell Activation ◽  
Humoral Immunity ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
Immunoglobulin M ◽  
Third Party ◽  
Cd4 T Cell ◽  
Specific Subset

Abstract Antibodies are typically thought of as the endpoint of humoral immunity that occur as the result of an adaptive immune response. However, affinity-matured antibodies can be present at the initiation of a new immune response, most commonly because of passive administration as a medical therapy. The current paradigm is that immunoglobulin M (IgM), IgA, and IgE enhance subsequent humoral immunity. In contrast, IgG has a “dual effect” in which it enhances responses to soluble antigens but suppresses responses to antigens on red blood cells (RBCs) (eg, immunoprophylaxis with anti-RhD). Here, we report a system in which passive antibody to an RBC antigen promotes a robust cellular immune response leading to endogenous CD4+ T-cell activation, germinal center formation, antibody secretion, and immunological memory. The mechanism requires ligation of Fcγ receptors on a specific subset of dendritic cells that results in CD4+ T-cell activation and expansion. Moreover, antibodies cross-enhance responses to a third-party antigen, but only if it is expressed on the same RBC as the antigen recognized by the antibody. Importantly, these observations were IgG subtype specific. Thus, these findings demonstrate that antibodies to RBC alloantigens can enhance humoral immunity in an IgG subtype-specific fashion and provide mechanistic elucidation of the enhancing effects.

scholarly journals Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs

2007 ◽  
Vol 205 (1) ◽  
pp. 105-115 ◽  
Author(s):  
Andrea J. Wolf ◽  
Ludovic Desvignes ◽  
Beth Linas ◽  
Niaz Banaiee ◽  
Toshiki Tamura ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Lymph Node ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Initial Activation ◽  
Local Lymph Node

The onset of the adaptive immune response to Mycobacterium tuberculosis is delayed compared with that of other infections or immunization, and allows the bacterial population in the lungs to expand markedly during the preimmune phase of infection. We used adoptive transfer of M. tuberculosis Ag85B-specific CD4+ T cells to determine that the delayed adaptive response is caused by a delay in initial activation of CD4+ T cells, which occurs earliest in the local lung-draining mediastinal lymph node. We also found that initial activation of Ag85B-specific T cells depends on production of antigen by bacteria in the lymph node, despite the presence of 100-fold more bacteria in the lungs. Although dendritic cells have been found to transport M. tuberculosis from the lungs to the local lymph node, airway administration of LPS did not accelerate transport of bacteria to the lymph node and did not accelerate activation of Ag85B-specific T cells. These results indicate that delayed initial activation of CD4+ T cells in tuberculosis is caused by the presence of the bacteria in a compartment that cannot be mobilized from the lungs to the lymph node, where initial T cell activation occurs.

scholarly journals Predicting the risk of re-infection from SARS-CoV-2 using the known pattern of adaptive immune response to previous human coronavirus outbreaks

2020 ◽  
Author(s):  
Ademola Samuel Ojo ◽  
Paul Toluwatope Okediji ◽  
Ayotemide P. Akin-Onitolo ◽  
Olusegun S. Ojo ◽  
Oluyinka Oladele Opaleye
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
The Body ◽  
Short Term ◽  
Adaptive Immune ◽  
Short And Long Term

This paper attempts to answer the question: are recovered COVID-19 patients protected from re-infection? This review draws evidence from comparisons between immune responses to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), which are phylogenetically closely related to Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). Relevant studies were identified and reviewed based on searches conducted using PubMed. Full-text original studies on short- and long-term immune responses to human coronaviruses were included. The immune dysfunction and clinical manifestations in SARS-CoV-2, SARS-CoV, and MERS-CoV were found to be similar. Infections with SARS-CoV and MERS-CoV trigger the production of antibodies and memory B- and T-cells. Serum IgM is detectable within 7 days, peak at 21-30 days and become undetectable by 180 days. IgG is detectable at 7 days, peak at 90 days, and decline to undetected levels by 2 years post-infection. Memory B- and T-cells persist in the body for up to 2 and 6 years respectively after initial infection. The short-term risk of SARS-CoV-2 re-infection is predictably low based on similarities in the short term adaptive immune response to kindred coronaviruses. However, more research will be required to determine the long-term adaptive immunity to SARS-CoV-2 and factors that may influence the existence of short- and long-term immunity against the virus.

Plant Phenolics and Lectins as Vaccine Adjuvants

2019 ◽  
Vol 20 (15) ◽  
pp. 1236-1243 ◽  
Author(s):  
Hernández-Ramos Reyna-Margarita ◽  
Castillo-Maldonado Irais ◽  
Rivera-Guillén Mario-Alberto ◽  
Ramírez-Moreno Agustina ◽  
Serrano-Gallardo Luis-Benjamín ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Adaptive Immune Response ◽  
The Body ◽  
Innate Immune ◽  
Vaccine Adjuvants ◽  
Plant Phenolics ◽  
Adaptive Immune ◽  
Foreign Substance

Background: The immune system is responsible for providing protection to the body against foreign substances. The immune system divides into two types of immune responses to study its mechanisms of protection: 1) Innate and 2) Adaptive. The innate immune response represents the first protective barrier of the organism that also works as a regulator of the adaptive immune response, if evaded the mechanisms of the innate immune response by the foreign substance the adaptive immune response takes action with the consequent antigen neutralization or elimination. The adaptive immune response objective is developing a specific humoral response that consists in the production of soluble proteins known as antibodies capable of specifically recognizing the foreign agent; such protective mechanism is induced artificially through an immunization or vaccination. Unfortunately, the immunogenicity of the antigens is an intrinsic characteristic of the same antigen dependent on several factors. Conclusion: Vaccine adjuvants are chemical substances of very varied structure that seek to improve the immunogenicity of antigens. The main four types of adjuvants under investigation are the following: 1) Oil emulsions with an antigen in solution, 2) Pattern recognition receptors activating molecules, 3) Inflammatory stimulatory molecules or activators of the inflammasome complex, and 4) Cytokines. However, this paper addresses the biological plausibility of two phytochemical compounds as vaccine adjuvants: 5) Lectins, and 6) Plant phenolics whose characteristics, mechanisms of action and disadvantages are addressed. Finally, the immunological usefulness of these molecules is discussed through immunological data to estimate effects of plant phenolics and lectins as vaccine adjuvants, and current studies that have implanted these molecules as vaccine adjuvants, demonstrating the results of this immunization.

scholarly journals Hypoxia/HIF Modulates Immune Responses

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 260
Author(s):  
Yuling Chen ◽  
Timo Gaber
Keyword(s):  
Immune Response ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Oxygen Availability ◽  
The Body ◽  
Low Oxygen ◽  
Adaptive Immune

Oxygen availability varies throughout the human body in health and disease. Under physiological conditions, oxygen availability drops from the lungs over the blood stream towards the different tissues into the cells and the mitochondrial cavities leading to physiological low oxygen conditions or physiological hypoxia in all organs including primary lymphoid organs. Moreover, immune cells travel throughout the body searching for damaged cells and foreign antigens facing a variety of oxygen levels. Consequently, physiological hypoxia impacts immune cell function finally controlling innate and adaptive immune response mainly by transcriptional regulation via hypoxia-inducible factors (HIFs). Under pathophysiological conditions such as found in inflammation, injury, infection, ischemia and cancer, severe hypoxia can alter immune cells leading to dysfunctional immune response finally leading to tissue damage, cancer progression and autoimmunity. Here we summarize the effects of physiological and pathophysiological hypoxia on innate and adaptive immune activity, we provide an overview on the control of immune response by cellular hypoxia-induced pathways with focus on the role of HIFs and discuss the opportunity to target hypoxia-sensitive pathways for the treatment of cancer and autoimmunity.

scholarly journals New Insights into the Role of PD-1 and Its Ligands in Allergic Disease

2021 ◽  
Vol 22 (21) ◽  
pp. 11898
Author(s):  
Miguel Angel Galván Morales ◽  
Josaphat Miguel Montero-Vargas ◽  
Juan Carlos Vizuet-de-Rueda ◽  
Luis M. Teran
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Adaptive Immune Response ◽  
Allergic Diseases ◽  
Main Role ◽  
Pathway Regulation

Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2 are receptors that act in co-stimulatory and coinhibitory immune responses. Signaling the PD-1/PD-L1 or PD-L2 pathway is essential to regulate the inflammatory responses to infections, autoimmunity, and allergies, and it has been extensively studied in cancer. Allergic diseases include asthma, rhinoconjunctivitis, atopic dermatitis, drug allergy, and anaphylaxis. These overactive immune responses involve IgE-dependent activation and increased CD4+ T helper type 2 (Th2) lymphocytes. Recent studies have shown that PD-L1 and PD-L2 act to regulate T-cell activation and function. However, the main role of PD-1 and its ligands is to balance the immune response; however, the inflammatory process of allergic diseases is poorly understood. These immune checkpoint molecules can function as a brake or a kick-start to regulate the adaptive immune response. These findings suggest that PD-1 and its ligands may be a key factor in studying the exaggerated response in hypersensitivity reactions in allergies. This review summarizes the current understanding of the role of PD-1 and PD-L1 and PD-L2 pathway regulation in allergic diseases and how this immunomodulatory pathway is currently being targeted to develop novel therapeutic immunotherapy.

scholarly journals First-in-human demonstration of splenic ultrasound stimulation for non-invasively controlling inflammation

2020 ◽  
Author(s):  
Rachel Stegeman Graham ◽  
Daniel P Zachs ◽  
Victoria Cotero ◽  
Catherine DAgostino ◽  
Despoina Ntiloudi ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
B Cell Activation ◽  
Cytokine Release ◽  
Non Invasive ◽  
Adaptive Immune ◽  
Ultrasound Stimulation ◽  
Human Demonstration

Hyperinflammation and uncontrolled cytokine release in infections and autoimmune diseases require therapy to reduce the innate immune response. Here, we present first in-human data showing reduction in pro-inflammatory cytokine release with ultrasound stimulation of the spleen in healthy subjects and in rheumatoid arthritis patients. Single cell RNA sequencing reveals a decrease in IL-1β and IL-8 transcript levels in circulating monocytes. There is also a down regulation of pathways involved in TNF and IL-6 production, and genes regulated by IFN and NFκB. Additional pre-clinical studies reveal that ultrasound can boost B cell activation and antibody production. Splenic ultrasound offers a new non-invasive therapy for treating hyperinflammation without compromising the adaptive immune response

scholarly journals Signaling of Macrophages that Contours the Tumor Microenvironment for Promoting Cancer Development

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 919 ◽  
Author(s):  
Justin K. Messex ◽  
Crystal J. Byrd ◽  
Geou-Yarh Liou
Keyword(s):  
Immune Response ◽  
Adaptive Response ◽  
Adaptive Immune Response ◽  
The Body ◽  
Foreign Material ◽  
Phagocytic Cells ◽  
Innate Response ◽  
Adaptive Immune ◽  
Tumor Growth And Metastasis ◽  
Fast Acting

The immune response is critical in the maintenance of an organism’s health. The immune response can be broken down into two groups. The innate response, which is fast-acting and rids the body of most foreign material before infection occurs, and the adaptive response, a more specific defense against pathogen composed mostly of antibody production and killer cells. Linking the two responses via cytokine and chemokine secretion are macrophages, motile phagocytic cells that ingest and present foreign material playing a role in the innate and adaptive immune response. Although macrophages are necessary for the survival of an organism, studies have also shown macrophages play a more sinister role in the initiation, progression, and metastasis in tumorous cells. In this comprehensive review, we show how macrophages induce such a response through abnormal cellular signaling and creating a cellular microenvironment conducive for tumor growth and metastasis, as well as the future outlook of this field.

scholarly journals Escherichia coli Prevents Phagocytosis-Induced Death of Macrophages via Classical NF-κB Signaling, a Link to T-Cell Activation

2006 ◽  
Vol 74 (10) ◽  
pp. 5989-6000 ◽  
Author(s):  
Heinrich V. Groesdonk ◽  
Silke Schlottmann ◽  
Friederike Richter ◽  
Michael Georgieff ◽  
Uwe Senftleben
Keyword(s):  
Escherichia Coli ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Adaptive Immune Response ◽  
Laboratory Strain ◽  
Pyrrolidine Dithiocarbamate ◽  
E Coli ◽  
Adaptive Immune

ABSTRACT NF-κB is a crucial mediator of macrophage inflammatory responses, but its role in the context of pathogen-induced adaptive immune responses has yet to be elucidated. Here, we demonstrate that classical NF-κB activation delays phagocytosis-induced cell death (PICD) in Raw 264.7 and bone marrow-derived macrophages (BMDMs) upon ingestion of bacteria from the Escherichia coli laboratory strain Top10. By expression of a nondegradable form of IκBα (superrepressor) and pyrrolidine dithiocarbamate treatment, prolonged activation of NF-κB upon bacterial coculture is suppressed, whereas initial induction is only partially inhibited. This activation pattern results in partial inhibition of cellular activation and reduced expression of costimulatory CD86. Notably, suppression of classical NF-κB activation does not influence bacterial uptake rates but is followed by increased production of oxygen radicals and enhanced intracellular killing in Raw macrophages. This is associated with reduced expression of NF-κB-dependent antiapoptotic c-IAP-2 and a loss of the mitochondrial transmembrane potential. Accordingly, NF-κB inhibition in Raw cells and BMDMs causes increased apoptotic rates within 12 h of bacterial ingestion. Interestingly, accelerated eradication of E. coli in NF-κB-inhibited macrophages is associated with reduced antigen-specific T-cell activation in macrophage-lymphocyte cocultures. These data suggest that E. coli inhibits PICD of macrophages via classical, antiapoptotic NF-κB activation and thus facilitates signaling to T cells. Subsequently, a proper adaptive immune response is likely to be generated. Conclusively, therapeutic inhibition of classical NF-κB activation in macrophages may hamper the initiation of adaptive immunity.

Sign in / Sign up

Export Citation Format

Share Document