Influenza Viruses: Innate Immunity and mRNA Vaccines

The innate immune system represents the first line of defense against influenza viruses, which cause severe inflammation of the respiratory tract and are responsible for more than 650,000 deaths annually worldwide. mRNA vaccines are promising alternatives to traditional vaccine approaches due to their safe dosing, low-cost manufacturing, rapid development capability, and high efficacy. In this review, we provide our current understanding of the innate immune response that uses pattern recognition receptors to detect and respond to mRNA vaccination. We also provide an overview of mRNA vaccines, and discuss the future directions and challenges in advancing this promising therapeutic approach.

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Innate immunity and the pneumococcus

Microbiology ◽

10.1099/mic.0.28551-0 ◽

2006 ◽

Vol 152 (2) ◽

pp. 285-293 ◽

Cited By ~ 52

Author(s):

Gavin K. Paterson ◽

Tim J. Mitchell

Keyword(s):

Innate Immunity ◽

Immune System ◽

Streptococcus Pneumoniae ◽

Immune Responses ◽

Innate Immune System ◽

Innate Immune ◽

First Line ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Made In

The innate immune system provides a non-specific first line of defence against microbes and is crucial both in the development and effector stages of subsequent adaptive immune responses. Consistent with its importance, study of the innate immune system is a broad and fast-moving field. Here we provide an overview of the recent key advances made in this area with relation to the important pathogen Streptococcus pneumoniae (the pneumococcus).

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Peptidoglycan O-Acetylation as a Virulence Factor: Its Effect on Lysozyme in the Innate Immune System

Antibiotics ◽

10.3390/antibiotics8030094 ◽

2019 ◽

Vol 8 (3) ◽

pp. 94 ◽

Cited By ~ 6

Author(s):

Ashley S. Brott ◽

Anthony J. Clarke

Keyword(s):

Immune System ◽

Virulence Factor ◽

Innate Immune System ◽

Innate Immune ◽

Host Immune System ◽

Gram Negative Bacteria ◽

First Line ◽

Structural Support ◽

Important Virulence Factor ◽

Novel Target

The peptidoglycan sacculus of both Gram-positive and Gram-negative bacteria acts as a protective mesh and provides structural support around the entirety of the cell. The integrity of this structure is of utmost importance for cell viability and so naturally is the first target for attack by the host immune system during bacterial infection. Lysozyme, a muramidase and the first line of defense of the innate immune system, targets the peptidoglycan sacculus hydrolyzing the β-(1→4) linkage between repeating glycan units, causing lysis and the death of the invading bacterium. The O-acetylation of N-acetylmuramoyl residues within peptidoglycan precludes the productive binding of lysozyme, and in doing so renders it inactive. This modification has been shown to be an important virulence factor in pathogens such as Staphylococcus aureus and Neisseria gonorrhoeae and is currently being investigated as a novel target for anti-virulence therapies. This article reviews interactions made between peptidoglycan and the host immune system, specifically with respect to lysozyme, and how the O-acetylation of the peptidoglycan interrupts these interactions, leading to increased pathogenicity.

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Mecanismos de control neuroinmune y la vía colinérgica antiinflamatoria

Tequio ◽

10.53331/teq.v1i2.9987 ◽

2018 ◽

Vol 1 (2) ◽

pp. 35-49

Author(s):

Yobana Pérez-Cervera ◽

Rafael Torres Rosas

Keyword(s):

Immune System ◽

Innate Immune System ◽

Inflammatory Diseases ◽

Basic Research ◽

Therapeutic Strategies ◽

Innate Immune ◽

First Line ◽

Neuronal Mechanisms ◽

Cholinergic Pathway ◽

Pharmacological Control

The innate immune system is the first line of defense involved in protecting against external pathogens and is crucial for survival. However, uncontrolled activation of the immune system can result in more damage than the factor that triggered them, causing atrophic scarring, chronic inflammation and even Systemic inflammation events such as Lupus, arthritis, Crohn’s disease or sepsis. Fortunately, there are neuronal mechanisms of inflammatory control which could be part of new therapeutic strategies to be studied for a better control of this type of pathologies. In the last decade, the cholinergic pathway has been described as part of the neuronal mechanisms that can be exogenous activated for the non-pharmacological control of inflammatory diseases, the aim of this review is to present the evidence in basic research and encourage the research in medical practice.

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Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System

Frontiers in Immunology ◽

10.3389/fimmu.2021.767175 ◽

2021 ◽

Vol 12 ◽

Author(s):

Richard Felix Kraus ◽

Michael Andreas Gruber

Keyword(s):

Immune System ◽

Innate Immune System ◽

Current Knowledge ◽

Immune Defense ◽

Innate Immune ◽

Human Organism ◽

Polymorphonuclear Cells ◽

Target Tissue ◽

First Line

Neutrophils (polymorphonuclear cells; PMNs) form a first line of defense against pathogens and are therefore an important component of the innate immune response. As a result of poorly controlled activation, however, PMNs can also mediate tissue damage in numerous diseases, often by increasing tissue inflammation and injury. According to current knowledge, PMNs are not only part of the pathogenesis of infectious and autoimmune diseases but also of conditions with disturbed tissue homeostasis such as trauma and shock. Scientific advances in the past two decades have changed the role of neutrophils from that of solely immune defense cells to cells that are responsible for the general integrity of the body, even in the absence of pathogens. To better understand PMN function in the human organism, our review outlines the role of PMNs within the innate immune system. This review provides an overview of the migration of PMNs from the vascular compartment to the target tissue as well as their chemotactic processes and illuminates crucial neutrophil immune properties at the site of the lesion. The review is focused on the formation of chemotactic gradients in interaction with the extracellular matrix (ECM) and the influence of the ECM on PMN function. In addition, our review summarizes current knowledge about the phenomenon of bidirectional and reverse PMN migration, neutrophil microtubules, and the microtubule organizing center in PMN migration. As a conclusive feature, we review and discuss new findings about neutrophil behavior in cancer environment and tumor tissue.

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Neutrophil abnormalities

10.1093/med/9780199568741.003.0295 ◽

2018 ◽

Author(s):

Malini Bhole

Keyword(s):

Clinical Practice ◽

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Bacterial Invasion ◽

Systemic Diseases ◽

First Line ◽

Life Threatening ◽

And Function

Neutrophils are an important component of the innate immune system, forming the first line of defence against bacterial invasion. Abnormalities in either neutrophil numbers or function lead to immunodeficiency disorders affecting the innate immune system, with a predisposition towards developing serious and often life-threatening infections. Alterations in neutrophil numbers and function may also be noted secondary to systemic diseases, where they may act as markers for ongoing disease processes. Most of the primary neutrophil disorders discussed in this chapter will present in childhood. In adults, acquired neutropenia is the commonest neutrophil abnormality encountered in clinical practice, although, rarely, some primary neutrophil defects may present.

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Autoinflammatory syndromes in neurology: when our first line of defence misbehaves

Practical Neurology ◽

10.1136/practneurol-2021-003031 ◽

2021 ◽

pp. practneurol-2021-003031

Author(s):

William K Diprose ◽

Anthony Jordan ◽

Neil E Anderson

Keyword(s):

Immune System ◽

Innate Immune System ◽

Neurological Disease ◽

Innate Immune ◽

First Line ◽

Autoinflammatory Syndromes ◽

Acute Phase Reactants ◽

Diverse Range ◽

Unexplained Fever ◽

Neurological Features

Autoinflammatory syndromes result in a defective innate immune system. They are characterised by unexplained fever and systemic inflammation involving the skin, muscle, joints, serosa and eyes, along with elevated acute phase reactants. Autoinflammatory syndromes are increasingly recognised as a cause of neurological disease with a diverse range of manifestations. Corticosteroids, colchicine and targeted therapies are effective if started early, and hence the importance of recognising these syndromes. Here, we review the neurological features of specific autoinflammatory syndromes and our approach (as adult neurologists) to their diagnosis.

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Pathophysiology of Mifepristone-Induced Septic Shock Due to Clostridium sordellii

Annals of Pharmacotherapy ◽

10.1345/aph.1g189 ◽

2005 ◽

Vol 39 (9) ◽

pp. 1483-1488 ◽

Cited By ~ 49

Author(s):

Ralph P Miech

Keyword(s):

Septic Shock ◽

Immune System ◽

Innate Immune System ◽

Glucocorticoid Receptors ◽

Data Extraction ◽

Rapid Development ◽

Innate Immune ◽

Data Sources ◽

Clostridium Sordellii ◽

Cytokine Responses

OBJECTIVE: To explain the role of mifepristone in medical abortions that results in fulminant and lethal septic shock due to Clostridium sordellii. DATA SOURCES: MEDLINE, PubMed, and Google Scholar databases were searched (1984–March 2005%). Key search terms were mifepristone, RU38486, RU486, Mifeprex, medical abortion, septic shock, innate immune system, cytokines, and Clostridium sordellii. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for the information related to the development of the understanding of the pathophysiology of mifepristone-induced septic shock due to C. sordellii. DATA SYNTHESIS: The mechanisms of action of mifepristone were incorporated into the pathophysiology of septic shock due to C. sordellii. Mifepristone, by blocking both progesterone and glucocorticoid receptors, interferes with the controlled release and functioning of cortisol and cytokines. Failure of physiologically controlled cortisol and cytokine responses results in an impaired innate immune system that results in disintegration of the body's defense system necessary to prevent the endometrial spread of C. sordellii infection. The abnormal cortisol and cytokine responses due to mifepristone coupled to the release of potent exotoxins and an endotoxin from C. sordellii are the major contributors to the rapid development of lethal septic shock. CONCLUSIONS: Theoretically, it appears that the mechanisms of mifepristone action favor the development of infection that leads to septic shock and intensifies the actions of multiple inflammatory cytokines, resulting in fulminant, lethal septic shock.

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Quantum Biotech and Internet of Virus Things: Towards A Theoretical Framework

Applied System Innovation ◽

10.3390/asi4020027 ◽

2021 ◽

Vol 4 (2) ◽

pp. 27

Author(s):

Prafulla Kumar Padhi ◽

Feranando Charrua-Santos

Keyword(s):

Messenger Rna ◽

Low Cost ◽

Rapid Development ◽

Theoretical Framework ◽

Effective Vaccine ◽

Research Activities ◽

Engine Design ◽

Low Cost Manufacturing ◽

Conventional Vaccine ◽

System Paradigm

Quantumization, the process of converting information into quantum (qubit) format, is a key enabler for propelling a new and distinct infrastructure in the pharmaceutical space. Quantum messenger RNA (QmRNA) technology, an indispensable constituent of quantum biotech (QB), is a compelling alternative to conventional vaccine methods because of its capacity for rapid development, high efficacy, and low-cost manufacturing to combat infectious diseases. Internet of Virus Things (IoVT), a biological version of Internet of Things (IoT), comprises applications to fight against pandemics and provides effective vaccine administration. The integration of QB and IoVT constitutes the QBIoVT system to advance the prospect of QmRNA vaccine discovery within a few days. This research disseminates the QBIoVT system paradigm, including architectural aspects, priority areas, challenges, applications, and QmRNA research engine design to accelerate QmRNA vaccines discovery. A comprehensive review of the literature was accomplished, and a context-centered methodology was applied to the QBIoVT paradigm forensic investigations to impel QmRNA vaccine discovery. Based on the above rumination, the principal motive for this study was to develop a novel QBIoVT theoretical framework which has not been produced through earlier theories. The proposed framework shall inspire future QBIoVT system research activities to improve pandemics detection and protection.

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lncRNAs Regulate Innate Immune Responses and Their Roles in Macrophage Polarization

Mediators of Inflammation ◽

10.1155/2018/8050956 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 13

Author(s):

Zhen Wang ◽

Ying Zheng

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Macrophage Polarization ◽

Noncoding Rnas ◽

Innate Immune ◽

Microbial Pathogens ◽

Innate Immune Responses ◽

First Line ◽

New Class

The innate immune system is the first line of defense against microbial pathogens. The activated innate immune system plays important roles in eliciting antimicrobial defenses. Despite the benefits of innate immune responses, excessive inflammation will cause host damage. Thus, tight regulation of these processes is required for the maintenance of immune homeostasis. Recently, a new class of long noncoding RNAs (lncRNAs) has emerged as important regulators in many physiological and pathological processes. Dysregulated lncRNAs have been found to be associated with excessive or uncontrolled inflammation. In this brief review, we summarize the roles of functional lncRNAs in regulating innate immune responses. We also discuss the roles of lncRNAs in macrophage polarization, an important molecular event in the innate immune responses.

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Innate Pathways of Immune Activation in Transplantation

Journal of Transplantation ◽

10.1155/2010/826240 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Todd V. Brennan ◽

Keri E. Lunsford ◽

Paul C. Kuo

Keyword(s):

Immune System ◽

Innate Immune System ◽

Critical Role ◽

Adaptive Immune System ◽

Innate Immune ◽

Microbial Pathogens ◽

Immune Recognition ◽

First Line ◽

Adaptive Immune

Studies of the immune mechanisms of allograft rejection have predominantly focused on the adaptive immune system that includes T cells and B cells. Recent investigations into the innate immune system, which recognizes foreign antigens through more evolutionarily primitive pathways, have demonstrated a critical role of the innate immune system in the regulation of the adaptive immune system. Innate immunity has been extensively studied in its role as the host's first-line defense against microbial pathogens; however, it is becoming increasingly recognized for its ability to also recognize host-derived molecules that result from tissue damage. The capacity of endogenous damage signals acting through the innate immune system to lower immune thresholds and promote immune recognition and rejection of transplant grafts is only beginning to be appreciated. An improved understanding of these pathways may reveal novel therapeutic targets to decrease graft alloreactivity and increase graft longevity.

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