Materiały źródłowe

• #1 The pathophysiology of anaphylaxis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5657389/

  Anaphylaxis is a severe, systemic hypersensitivity reaction that is rapid in onset and characterized by life-threatening airway, breathing, and/or circulatory problems, and that is usually associated with skin and mucosal changes. […] This review will describe current understanding of the immunopathogenesis and pathophysiology of anaphylaxis, focusing on the roles of IgE and IgG antibodies, immune effector cells, and mediators thought to contribute to examples of the disorder. […] The major pathophysiological changes observed during anaphylaxis, and some of the mediators that are thought to contribute to them, are shown in Figure 2. […] IgE antibodies undeniably can play an important role in conferring immunological specificity to effector cell activation in anaphylaxis and other allergic diseases.

• #1

  https://step2.medbullets.com/dermatology/120070/anaphylaxis

  A potentially life-threatening systemic allergic reaction can result in airway obstruction as well as cardiovascular collapse. […] Type I hypersensitivity reaction mast cell and basophil activation leads to inflammatory mediator release via IgE and non-IgE mediated mechanisms. […] epinephrine mechanism of action 1 agonism results in increased vasoconstriction and decreases mucosal edema. […] 1 agonism results in increased chronotropy and ionotropy. […] 2 agonism results in bronchodilation and decreases inflammatory mediator release from mast cells and basophils. […] Complications include airway obstruction and cardiovascular collapse.

• #1 Pathophysiology of anaphylaxis – UpToDate

  https://www.uptodate.com/contents/pathophysiology-of-anaphylaxis

  Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. It most often results from immunologic reactions to foods, medications, and insect stings, although it can also be induced through nonimmunologic mechanisms by any agent capable of producing a sudden, systemic degranulation of mast cells or basophils. […] The mechanism responsible for most cases of human anaphylaxis involves immunoglobulin E (IgE). Possible alternative mechanisms remain incompletely understood. Environmental exposures and complex genetic factors may also have important roles, although they are not explored in this review. […] The term „anaphylaxis” has traditionally been reserved for IgE-dependent events, and the term „anaphylactoid reaction” has been used to describe IgE-independent events, although the two reactions are often clinically indistinguishable. The World Allergy Organization (WAO) has proposed discarding this nomenclature. The WAO categorizes anaphylaxis as either immunologic or nonimmunologic, and this is the terminology used in this review.

• #1 Pathophysiology of anaphylaxis – UpToDate

  https://www.uptodate.com/contents/pathophysiology-of-anaphylaxis/print

  Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. […] The mechanism responsible for most cases of human anaphylaxis involves immunoglobulin E (IgE). Possible alternative mechanisms remain incompletely understood. Environmental exposures and complex genetic factors may also have important roles, although they are not explored in this review. […] The term „anaphylaxis” has traditionally been reserved for IgE-dependent events, and the term „anaphylactoid reaction” has been used to describe IgE-independent events, although the two reactions are often clinically indistinguishable. The World Allergy Organization (WAO) has proposed discarding this nomenclature. The WAO categorizes anaphylaxis as either immunologic or nonimmunologic.

• #1 Anaphylaxis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135065-overview

  Anaphylaxis is an acute, potentially fatal, multiorgan system reaction caused by the release of chemical mediators from mast cells and basophils. The classic form involves prior sensitization to an allergen with later reexposure, producing symptoms via an immunologic mechanism. […] The traditional nomenclature for anaphylaxis reserves the term anaphylactic for reactions mediated by immunoglobulin E (IgE) and the term anaphylactoid for non-IgE-mediated reactions, which can be clinically indistinguishable. The World Allergy Organization has recommended replacing this terminology with immunologic (IgE-mediated and nonIgE-mediated [eg, IgG and immune complex complementmediated]) and nonimmunologic anaphylaxis (events resulting in sudden mast cell and basophil degranulation in the absence of immunoglobulins).

• #1 The pathophysiology of anaphylaxis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5657389/

  IgE binds to the high affinity receptor, FcRI, on the surface of blood basophils and tissue resident mast cells, and (in humans to a greater extent than in mice) other cell types, including neutrophils, eosinophils, monocytes and dendritic cells, and platelets. […] Upon exposure to a bi- or multi-valent allergen, crosslinking of FcRI-bound IgE induces activation of mast cells and basophils, and the immediate release of preformed mediators such as histamine and various proteases, as well as de novo synthesis of many inflammatory mediators such as certain leukotrienes, prostaglandins, and cytokines. […] The importance of that reaction was demonstrated 50 years ago, when different groups realized that purified IgE was capable of transferring skin reactivity from a sensitized human subjects to naive hosts.

• #1 Anaphylaxis.html

  https://www.bio.davidson.edu/courses/immunology/students/spring2006/witcher/anaphylaxis.html

  (1) Antigen-presenting cell internalizes antigen. (2) The APC processes the internalized antigen. (3) The APC presents the processed peptide to CD4+ T lymphocytes via MHC II. (4) After the peptide is presented, the T cell differentiates into TH2 lymphocytes and produces IL-4, IL-5, IL-9, and IL-13. (5) IL-4 and IL-13 cause B cell immunoglobulin isotype switching to IgE. (6) The circulating IgE binds to the IgE receptors on mast cells. (7) Antigen similar to the original antigen cross-links the mast cell surface-bound IgE, resulting in cellular degranulation. Degranulation releases histamine, tryptase, and other mediators that produce the symptoms of anaphylaxis (Anaesthesia UK, 2005).

• #1 Anaphylaxis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135065-overview

  Under rigid experimental conditions, histamine infusion alone is sufficient to produce most of the symptoms of anaphylaxis. Histamine mediates its effects through activation of histamine 1 (H1) and histamine 2 (H2) receptors. […] Vasodilation, hypotension, and flushing are mediated by both H1 receptors and H1 receptors. H1 receptors alone mediate coronary artery vasoconstriction, tachycardia, vascular permeability, pruritus, bronchospasm, and rhinorrhea. H2 receptors increase atrial and ventricular contractility, atrial chronotropy, and coronary artery vasodilation. H3 receptors in experimental models of canine anaphylaxis appear to influence cardiovascular responses to norepinephrine. The importance of H3 receptors in humans is unknown.

• #1 Anaphylactic Shock | IntechOpen

  https://www.intechopen.com/chapters/68438

  Once activated, mast cells and basophils release a cascade of mediators which cause physiologic changes, activate other immunology pathways, and attract other immune cells. Preformed mediators are released immediately upon activation including histamine, tryptase, heparin, and chymase. Over several minutes additional mediators are generated including platelet activating factor, leukotrienes, and prostaglandins. Various cytokines and chemokines are generated over several hours further propagate the inflammatory response. […] Histamine has long been considered the principal mediator of anaphylaxis, and concentrations of histamine correlate with symptom severity. Histamine acts on receptors to cause vasodilation and increased permeability, bronchoconstriction, and increase mucus secretion. […] Platelet activating factor (PAF) has been increasingly recognized as important in the pathophysiology of anaphylaxis. In PAF receptor knockout mice, symptoms of anaphylaxis are reduced. In humans PAF levels in the serum directly correlates with the severity of anaphylaxis symptoms.

• #1 Anaphylaxis.html

  https://www.bio.davidson.edu/courses/immunology/students/spring2006/witcher/anaphylaxis.html

  Anaphylaxis occurs when a person is reexposed to a specific antigen that cross-links antigen-specific IgE molecules, which are bound to mast cells and basophils. This leads to activation and degranulation of mast cells and basophils. Preformed mediators, such as histamine and tryptase, within the mast cell and basophil are released in degranulation. The metabolism of arachidonic acid in the cell membrane produces other mediators, such as prostaglandins and leukotrienes. These mediators act on receptors to induce mucus production, pruritus, vascular permeability, smooth-muscle constriction, and other symptoms of anaphylaxis (Rusznak, 2002). […] Rapid release of large quantities of mediators systemically will cause capillary leakage and mucosal edema, resulting in shock and asphyxia (Ewan, 1998).

• #1 Anaphylaxis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135065-overview

  Additional mediators activate other pathways of inflammation: the neutral proteases, tryptase and chymase; proteoglycans such as heparin and chondroitin sulfate; and chemokines and cytokines. These mediators can activate the kallikrein-kinin contact system, the complement cascade, and coagulation pathways. The development and severity of anaphylaxis also depend on the responsiveness of cells targeted by these mediators. […] Interleukin (IL)4 and IL-13 are cytokines important in the initial generation of antibody and inflammatory cell responses to anaphylaxis. No comparable studies have been conducted in humans, but anaphylactic effects in mice depend on IL-4R-dependent IL-4/IL-13 activation of the transcription factor, STAT-6. […] Additional mediators include newly generated lipid-derived mediators such as prostaglandin D2, leukotriene B4, and platelet-activating factor (PAF), as well as the cysteinyl leukotrienes, such as LTC4, LTD4, and LTE4. These mediators further contribute to the proinflammatory cascade seen in anaphylaxis.

• #1 Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond

  https://www.mdpi.com/1422-0067/22/15/7785

  The role of PAF as a potent mediator of anaphylaxis has been established in mouse models of anaphylaxis as well as in human subjects. […] The severity of anaphylaxis has also been inversely correlated with a lower level of PAF-AH activity. […] The platelet activating factor is the most potent mast cell mediator identified to date and is associated with decreased cardiac output, vascular hyperpermeability, smooth muscle contraction, hypovolemia, and cardiac collapse. […] The endothelial barrier can be disrupted by a plethora of factors released during anaphylaxis or during infectious or inflammatory states. […] These permeability-enhancing factors include TNF-α, IL-6, histamine, PAF, kinins and reactive oxygen species. […] Activated mast cells in anaphylaxis can express histamine, TNF-α, PAF and VEGF, all of which have been shown to increase vascular permeability by influencing function of AJs.

• #1 Anaphylaxis | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-018-0283-4

  Anaphylaxis is an acute, potentially fatal systemic allergic reaction with varied mechanisms and clinical presentations. […] Most episodes of anaphylaxis are triggered through an immunologic mechanism involving immunoglobulin E (IgE) which leads to mast cell and basophil activation and the subsequent release of inflammatory mediators such as histamine, platelet activating factor, leukotrienes, tryptase and prostaglandins. […] The diagnosis of anaphylaxis during an acute episode is based primarily on clinical signs and symptoms. […] The clinical history is the most important tool to establish the cause of anaphylaxis and must take precedence over diagnostic tests. […] The diagnosis of a specific cause of anaphylaxis may be supported by the results of skin tests and/or in vitro IgE tests.

• #1 The pathophysiology of anaphylaxis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5657389/

  Such IgE-mediated anaphylaxis is abrogated in mice lacking the high affinity IgE receptor FcRI, as well as in mast cell-deficient mice, highlighting the importance of IgE-mediated mast cell activation in such models of anaphylaxis. […] The fact that some patients experience anaphylaxis despite having undetectable levels of circulating allergen-specific IgE suggests the existence of IgE-independent pathways of anaphylaxis. […] Activation of the complement cascade occurs in response to many stimuli, and leads to generation of small polypeptides: C3a, C4a and C5a, also named anaphylatoxins, which are potent inflammatory mediators. […] Injection of low doses of C3a, C4a or C5a into the skin of healthy volunteers induces immediate wheal and flare reactions. […] Several lines of evidence suggest that basophils participate in anaphylaxis.

• #1 Novel Mechanism Discovered for Anaphylaxis Cases During Surgery

  https://www.uspharmacist.com/article/novel-mechanism-discovered-for-anaphylaxis-cases-during-surgery

  The use of certain drugs during surgery can result in anaphylactic shock, and the exacerbated allergic reaction is explained in 80% or more of those cases by the presence of antidrug antibodies of the immunoglobulin E (IgE) class. […] A study team involving the Institut Pasteur, Inserm, the Paris Public Hospital Network, the CNRS, Paris-Sud University, and Sorbonne University identified a new pathological mechanism responsible for the unexplained cases: neutrophils activated by antibodies of the immunoglobulin G (IgG) class. […] This study reveals that they may be involved in humans in another reaction that is harmful for the body, anaphylaxis, pointed out coauthor Pierre Bruhns, PhD, Inserm Research Director and Head of the Institut Pasteurs Antibodies in Therapy and Pathology Unit. […] The study explained that IgG antibodies activate neutrophils and that concentrations of anti-NMBA IgG and markers of Fc gamma receptor activation, platelet-activating factor release, and neutrophil activation correlated with anaphylaxis severity.

• #1 Novel Mechanism Discovered for Anaphylaxis Cases During Surgery

  https://www.uspharmacist.com/article/novel-mechanism-discovered-for-anaphylaxis-cases-during-surgery

  The IgG-neutrophil pathway was also identified in most cases of shock in which the traditional IgE-dependent mechanism was observed, according to the authors, who posited that the two mechanisms might work together to increase the severity of many cases of anaphylaxis. […] These findings elucidate 10 to 20% of cases of anaphylactic shock that previously had no biological explanation.

• #1 Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond

  https://www.mdpi.com/1422-0067/22/15/7785

  The activation of the contact system results in inflammatory responses, coagulation cascades with vascular thrombosis, fibrinolysis and complement activation. […] Mast cell-derived heparin has been shown to activate the contact system and may play a role in the hypotension and disseminated intravascular coagulation (DIC) seen in severe anaphylactic reactions.

• #1 Anaphylaxis – Wikipedia

  https://en.wikipedia.org/wiki/Anaphylaxis

  Anaphylaxis is a severe allergic reaction of rapid onset affecting many body systems. […] It is due to the release of inflammatory mediators and cytokines from mast cells and basophils, typically due to an immunologic reaction but sometimes non-immunologic mechanism. […] In the immunologic mechanism, immunoglobulin E (IgE) binds to the antigen (the foreign material that provokes the allergic reaction). Antigen-bound IgE then activates FcRI receptors on mast cells and basophils. This leads to the release of inflammatory mediators such as histamine. These mediators subsequently increase the contraction of bronchial smooth muscles, trigger vasodilation, increase the leakage of fluid from blood vessels, and cause heart muscle depression. […] There is also a non-immunologic mechanism that does not rely on IgE, but it is not known if this occurs in humans. […] Non-immunologic mechanisms involve substances that directly cause the degranulation of mast cells and basophils. These include agents such as contrast medium, opioids, temperature (hot or cold), and vibration.

• #1 Food allergies and food-induced anaphylaxis: role of cofactors

  https://www.e-cep.org/journal/view.php?number=20125555382

  The role of aspirin and NSAID use as cofactors has not been fully evaluated in children and adolescents. However, NSAID use must be considered a cofactor, especially in adolescents with severe food allergies. […] The phenomenon of cofactors is well known but frequently neglected. Cofactors such as exercise, infections, NSAID use, dehydration, and alcohol intake can increase intestinal permeability and result in increased antigen uptake, thereby causing allergic symptoms.

• #1 Anaphylaxis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135065-overview

  The physiologic responses to the release of anaphylaxis mediators include smooth muscle spasm in the respiratory and gastrointestinal (GI) tracts, vasodilation, increased vascular permeability, and stimulation of sensory nerve endings. Increased mucous secretion and increased bronchial smooth muscle tone, as well as airway edema, contribute to the respiratory symptoms observed in anaphylaxis. […] Cardiovascular effects result from decreased vascular tone and capillary leakage. Hypotension, cardiac arrhythmias, syncope, and shock can result from intravascular volume loss, vasodilation, and myocardial dysfunction. Increased vascular permeability can produce a shift of 35% of vascular volume to the extravascular space within 10 minutes. […] These physiologic events lead to some or all of the classic symptoms of anaphylaxis: flushing; urticaria/angioedema; pruritus; bronchospasm; laryngeal edema; abdominal cramping with nausea, vomiting, and diarrhea; and feeling of impending doom.

• #1 Researchers identify a new molecular mechanism related to severe anaphylaxis

  https://www.clinicbarcelona.org/en/news/researchers-identify-a-new-molecular-mechanism-related-to-severe-anaphylaxis

  Anaphylaxis is a systemic allergic reaction that can affect the skin, the gastrointestinal tract, the respiratory system and the cardiovascular system. The most severe form of anaphylaxis is anaphylactic shock, which features hypotension and can cause death. […] The molecular mechanisms that cause the severity of these kinds of reactions is still unknown. […] The results, published in the Journal of Allergy and Clinical Immunology, revealed a new molecular mechanism that can control the degree of severity in an anaphylactic reaction. […] The study combines clinical data from the patient with severe anaphylaxis and carrier of a mutation in the KARS gen, with biochemical, functional and structural data that show an anomalous function of the LysRS protein, coded by this gen, notes Margarita Martn.

• #1 Researchers identify a new molecular mechanism related to severe anaphylaxis

  https://www.clinicbarcelona.org/en/news/researchers-identify-a-new-molecular-mechanism-related-to-severe-anaphylaxis

  The LysRS protein is an enzyme with a dual function. It plays a key role in the protein synthesis, and it is regulated by the phosphorylation in the highaffinity receptor for immunoglobulin E (IgE) and activates the MITF transcription factor, which takes part in the transcription of proinflammatory mediators in the mast cell, a type of cells in the immune system that act as inflammatory processes caused by allergic reactions. […] From the biochemical perspective, results show that the replacement of a proline for an arginine in the LysRS protein aminoacid 542 causes structural changes. These changes affect the protein, which moves towards the nucleus and stops its function in the protein synthesis, activating the MITF transcription factor when there is a lack of stimuli. This cause sthe increase in the synthesis of proinflammatory mediators and an activation of the mast cell in presence of the allergen, which drives to an anaphylactic shock. The new mechanism identified in this study involves the signalling base IgE-LysRWS-MITF, which would control the degree of severity in an anaphylactic reaction, says Margarita Martn.

• #1 The pathophysiology of anaphylaxis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5657389/

  Mast cells are viewed as key players in IgE-dependent allergies and anaphylaxis. […] There is compelling evidence of activation of mast cells during acute anaphylaxis. […] Anaphylaxis induces changes in levels of many other mediators which could potentially contribute (positively or negatively) to the clinical signs and symptoms. […] Anaphylaxis may have effects that can reduce the toxic effects of certain arthropod or reptile venoms.

• #1 Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond

  https://www.mdpi.com/1422-0067/22/15/7785

  An endotype has been defined as “a compilation of disease mechanisms explaining disease expression within certain groups of patients”, and in the case of anaphylaxis, endotypes have included allergic/immune- (IgE or IgG-mediated), contact system-, cytokine-(cytokine release reactions or CRRs—which could be mixed due to co-occurrence of IgE-mediated reactions and cytokine storm reactions or CSRs), mast cell activation- (direct mast cell activation or clonal mast cell disorders), and complement-mediated reactions. […] The role of mast cell signaling, the mediators expressed and their effects on vascular permeability and shock are reviewed below. […] Mast cell-derived cytokines, histamine, leukotrienes, prostanoids and PAF regulate vascular instability, barrier dysfunction of endothelial cells and contribute to edema formation.

• #1 Animal Models of IgE Anaphylaxis

  https://www.mdpi.com/2079-7737/12/7/931

  Anaphylaxis is the most severe form of allergic reactions and can be life-threatening. […] Animal models have been developed to replicate human anaphylaxis and explore its pathophysiology. […] The classical pathway of anaphylaxis involves immunoglobulin (Ig) E antibodies, but other alternative pathways have been described in humans. […] Two independent mechanisms have been described in animal models of anaphylaxis, each of them involving antibodies of a distinct isotype (IgE or IgG); the first of these, referred to as the classical pathway, is the subject of this review. […] Although other mechanisms have been described, the classical pathway of anaphylaxis involves IgE antibodies bound to their high-affinity receptors (FcεRI), which are mainly expressed on the surface of mast cells in tissues and basophils in circulation.

• #1 ASCIA Guidelines Acute management of anaphylaxis – Australasian Society of Clinical Immunology and Allergy (ASCIA)

  https://www.allergy.org.au/hp/papers/acute-management-of-anaphylaxis-guidelines

  Anaphylaxis is highly likely when any one of the following two criteria are fulfilled: Acute onset of an illness (minutes to several hours) with simultaneous involvement of the skin, mucosal tissue, or both (e.g. generalized hives, pruritus or flushing, swollen lips-tongue-uvula), and at least one of the following: a) Respiratory compromise (e.g. dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia). b) Reduced blood pressure or associated symptoms of end-organ dysfunction (e.g. hypotonia [collapse], syncope, incontinence). c) Severe gastrointestinal symptoms (e.g. severe crampy abdominal pain, repetitive vomiting), especially after exposure to non-food allergens. […] Anaphylaxis is the first line treatment for anaphylaxis and acts to reduce airway mucosal oedema, induce bronchodilation, induce vasoconstriction and increase strength of cardiac contraction.

• #1 ASCIA Guidelines Acute management of anaphylaxis – Australasian Society of Clinical Immunology and Allergy (ASCIA)

  https://www.allergy.org.au/hp/papers/acute-management-of-anaphylaxis-guidelines

  Adrenaline is the first line treatment for anaphylaxis and acts to reduce airway mucosal oedema, induce bronchodilation, induce vasoconstriction and increase strength of cardiac contraction. […] If there is an inadequate response after 2-3 adrenaline doses, or deterioration of the patient, start IV adrenaline infusion, given by staff trained in its use or in liaison with an emergency specialist. […] Caution: IV boluses of adrenaline are NOT recommended without specialised training as they may increase the risk of cardiac arrhythmia.

• #1 What is Epinephrine? – Allergy & Asthma Network

  https://allergyasthmanetwork.org/anaphylaxis/what-is-epinephrine/

  Epinephrine is the treatment for anaphylaxis. Anaphylaxis is a severe allergic reaction that can occur due to: […] Epinephrine for anaphylaxis reduces or reverses these severe symptoms very quickly. It opens the airways and reduces swelling. It helps maintain heart function and blood pressure. As epinephrine causes the blood to be diverted away from the skin, it can help reduce hives and itching. […] Epinephrine triggers a sudden burst of adrenaline to multiple areas of the body simultaneously. Your heart begins to beat faster and stronger. Your airways open. The blood goes to your vital organs and away from your skin. […] Epinephrine is the only medication that can reverse the life-threatening symptoms of anaphylaxis.

• #1 Anaphylaxis – Core EM

  https://coreem.net/core/anaphylaxis/

  Mechanism […] Beta-1 adrenergic agonist: augments inotropy and chronotropy […] Beta-2 adrenergic agonist: triggers bronchodilation and decreases mediator release […] Alpha-1 adrenergic agonist: increases vasoconstriction, peripheral vascular resistance, reduces mucosal edema […] Anaphylaxis Refractory to Epinephrine […] Methylene blue […] Inhibits nitric oxide synthase and guanylate cyclase to increase systemic vascular resistance.

• #1 Food allergies and food-induced anaphylaxis: role of cofactors

  https://www.e-cep.org/journal/view.php?number=20125555382

  Food allergies and food-induced anaphylaxis are important health problems. Several cofactors modulating the onset of anaphylaxis have been identified. […] Cofactors reportedly play a role in approximately 30% of anaphylactic reactions in adults and 14%18.3% in children. […] The mechanisms of action of cofactors have not yet been fully identified. […] The main cofactors in children and adolescents differ from those in adults. […] In adults, drugs and alcohol are the most frequent cofactors, followed by physical exercise. In contrast, exercise and concomitant infections were the most frequent cofactors of anaphylaxis in children and adolescents. […] The mechanisms of cofactors involved in allergic reactions are complex and have diverse pathways. […] Two major mechanisms of cofactor-induced modulation eliciting anaphylaxis have been indicated: increased bioavailability of the allergen (increased intestinal permeability) and decreased activation threshold at the cellular level.

• #1 Understanding the mechanisms of anaphylaxis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2683407/

  The present review considers recent reports that identify the roles of key intermediate signaling components and mediators during and after mast cell activation and degranulation leading to anaphylaxis. […] Mechanisms of anaphylaxis are becoming better understood as the interaction of several regulatory systems in the mast cell activation and degranulation signaling cascade. […] Understanding the mechanisms of mast cell activation and degranulation is critical to understanding the mechanisms of anaphylaxis. […] Anaphylaxis, for the most part, is believed to arise from the activation of mast cells and basophils through a mechanism generally understood to involve crosslinking of immunoglobulin (Ig) E and aggregation of the high-affinity receptors for IgE, FcRI. […] The activation of intracellular signaling cascades results in rapid degranulation of mast cells, the generation of arachidonic acid metabolites (lipid mediators), and later production of cytokines and chemokines.

• #1

  https://journals.lww.com/co-allergy/Fulltext/2008/08000/Understanding_the_mechanisms_of_anaphylaxis.00007.aspx?generateEpub=Article%7Cco-allergy:2008:08000:00007%7C10.1097/aci.0b013e3283036a90%7C

  Mechanisms of anaphylaxis are becoming better understood as the interaction of several regulatory systems in the mast cell activation and degranulation signaling cascade. […] Therefore, understanding the mechanisms of mast cell activation and degranulation is critical to understanding the mechanisms of anaphylaxis. Recent reports have identified important regulatory components of the signaling cascade and, consequently, potential targets for therapeutic intervention.

• #1 Understanding the mechanisms of anaphylaxis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2683407/

  Activated Fyn constitutes a second, tyrosine kinase-mediated pathway leading to mast cell degranulation. […] Regulation of calcium concentration plays a central role in mast cell degranulation, and several calcium channels now appear to contribute to maintaining the threshold of degranulation through negative and positive regulation. […] Although S1P appears as a newly recognized mediator of anaphylaxis, histamine, tryptase, leukotrienes, prostaglandins, TNF-, and PAF, generated by mast cell or basophil activation, have been long shown to trigger the major physiological manifestations of anaphylaxis. […] The complex regulation of mast cell signaling unfolding in these recent studies highlights the sensitivity of the system to dysregulation arising from a single component. […] The adoption of a consensus definition and diagnostic criteria is a significant step in improving the identification and treatment of anaphylaxis and will contribute to improved estimates of occurrence. […] A better understanding of the mechanisms of anaphylaxis is beginning to unfold through the examination of mast cell signaling.

• #1 New molecular mechanism for anaphylaxis

  https://frontlinegenomics.com/new-molecular-mechanism-for-anaphylaxis/

  Researchers have a revealed a new molecular mechanism that can determine the degree of severity during anaphylaxis. […] Unfortunately, within the last few decades, the incidence of anaphylaxis has risen at an alarming rate with the underlying molecular mechanisms responsible still largely unknown. Therefore, understanding the molecular basis of anaphylactic shock is important to develop new biomarkers and effective preventative measures and/or treatments. […] The team found that the mutation affects the location of the protein, moving the protein towards the nucleus and preventing its function in protein synthesis. It also activates the MITF transcription factor when there is a lack of stimuli; thereby, increasing the synthesis of proinflammatory mediators and activating mast cells. The team identified that the new mechanism, involving the signalling pathway IgE-LysRWS-MITF, can control the degree of severity in an anaphylactic reaction. […] This study for the first time explains the switching mechanism from translation to transcription of LysRS at a molecular level and how specific mutations in the KARS gene regulate its function.

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