Immunological responses to envenomation

Venoms are complex mixtures of toxic compounds delivered by bite or sting. In humans, the consequences of envenomation range from self-limiting to lethal. Critical host defence against envenomation comprises innate and adaptive immune strategies targeted towards venom detection, neutralisation, detoxification, and symptom resolution. In some instances, venoms mediate immune dysregulation that contributes to symptom severity. This review details the involvement of immune cell subtypes and mediators, particularly of the dermis, in host resistance and venom-induced immunopathology. We further discuss established venom-associated immunopathology, including allergy and systemic inflammation, and investigate Irukandji syndrome as a potential systemic inflammatory response. Finally, this review characterises venom-derived compounds as a source of immune modulating drugs for treatment of disease

Allergic diseases in the elderly: biological characteristics and main immunological and non-immunological mechanisms

Life expectancy and the number of elderly people are progressively increasing around the world. Together with other pathologies, allergic diseases also show an increasing incidence in geriatric age. This is partly due to the growing emphasis on a more accurate and careful diagnosis of the molecular mechanisms that do not allow to ignore the real pathogenesis of many symptoms until now unknown, and partly to the fact that the allergic people from 20 years ago represent the elderly population now. Moreover, environmental pollution predisposes to the onset of allergic asthma and dermatitis which are the result of internal pathologies more than the expression of allergic manifestations. At the same time the food contamination permits the onset of allergic diseases related to food allergy. In this review we provide the state of the art on the physiological changes in the elderly responsible for allergic diseases, their biological characteristics and the major immunological and extra immunological mechanisms. Much emphasis is given to the management of several diseases in the elderly, including anaphylactic reactions. Moreover, some new features are discussed, such as management of asthma with the support of physical activity and the use of the AIT as prevention of respiratory diseases and for the purpose of a real and long lasting benefit. The mechanisms of adverse reactions to drugs are also discussed, due to their frequency in this age, especially in polytherapy regimens. Study of the modifications of the immune system is also of great importance, as regards to the distribution of the lymphocytes and also the presence of a chronic inflammatory disease related to the production of cytokines, especially in prevision of all the possible therapies to be adopted to allow an active and healthy agin

Covid-19 disease, women’s predominant non-heparin vaccine-induced thrombotic thrombocytopenia and kounis syndrome: A passepartout cytokine storm interplay

Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitute one of the deadliest pandemics in modern history demonstrating cardiovascular, gastrointestinal, hematologic, mucocutaneous, respiratory, neurological, renal and testicular manifestations and further complications. COVID-19-induced excessive immune response accompanied with uncontrolled release of cytokines culminating in cytokine storm seem to be the common pathogenetic mechanism of these complications. The aim of this narrative review is to elucidate the relation between anaphylaxis associated with profound hypotension or hypoxemia with pro-inflammatory cytokine release. COVID-19 relation with Kounis syndrome and post-COVID-19 vaccination correlation with heparin-induced thrombocytopenia with thrombosis (HITT), especially serious cerebral venous sinus thrombosis, were also reviewed. Methods: A current literature search in PubMed, Embase and Google databases was performed to reveal the pathophysiology, prevalence, clinical manifestation, correlation and treatment of COVID-19, anaphylaxis with profuse hypotension, Kounis acute coronary syndrome and thrombotic events post vaccination. Results: The same key immunological pathophysiology mechanisms and cells seem to underlie COVID-19 cardiovascular complications and the anaphylaxis-associated Kounis syndrome. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, plaque rupture and microthrombi formation, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. COVID-19-interrelated vaccine excipients as polysorbate, polyethelene glycol (PEG) and trometamol constitute potential allergenic substances. Conclusion: Better acknowledgement of the pathophysiological mechanisms, clinical similarities, multiorgan complications of COVID-19 or other viral infections as dengue and human immunodeficiency viruses along with the action of inflammatory cells inducing the Kounis syndrome could identify better immunological approaches for prevention, treatment of the COVID-19 pandemic as well as post-COVID-19 vaccine adverse reactions

Allergic diseases in the elderly: Biological characteristics and main immunological and non-immunological mechanisms

Life expectancy and the number of elderly people are progressively increasing around the world. Together with other pathologies, allergic diseases also show an increasing incidence in geriatric age. This is partly due to the growing emphasis on a more accurate and careful diagnosis of the molecular mechanisms that do not allow to ignore the real pathogenesis of many symptoms until now unknown, and partly to the fact that the allergic people from 20 years ago represent the elderly population now. Moreover, environmental pollution predisposes to the onset of allergic asthma and dermatitis which are the result of internal pathologies more than the expression of allergic manifestations. At the same time the food contamination permits the onset of allergic diseases related to food allergy. In this review we provide the state of the art on the physiological changes in the elderly responsible for allergic diseases, their biological characteristics and the major immunological and extra immunological mechanisms. Much emphasis is given to the management of several diseases in the elderly, including anaphylactic reactions. Moreover, some new features are discussed, such as management of asthma with the support of physical activity and the use of the AIT as prevention of respiratory diseases and for the purpose of a real and long lasting benefit. The mechanisms of adverse reactions to drugs are also discussed, due to their frequency in this age, especially in polytherapy regimens. Study of the modifications of the immune system is also of great importance, as regards to the distribution of the lymphocytes and also the presence of a chronic inflammatory disease related to the production of cytokines, especially in prevision of all the possible therapies to be adopted to allow an active and healthy aging

SARS-CoV-2 Disease through Viral Genomic and Receptor Implications: An Overview of Diagnostic and Immunology Breakthroughs

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which is believed to have originated in China towards the end of November 2019, has now spread across the globe, causing a pandemic in 192 countries. The World Health Organization has called it the SARS-CoV-2 pandemic. Rapid dissemination of the virus occurs mainly through the saliva (Flügge’s droplets) and aerosol, together with nasal and lachrymal passages. The literature associated with the recent advancement in terms of rapid diagnostics and SARS-CoV-2 vaccines has thoroughly studied the role of ACE2 receptors and Furin, as well as viral agent access into the host cell and its significant persistence at the level of the oral mucosa, which represents the main access to the virus. The purpose of this review was to underline the processes of SARS-CoV-2 infection mechanisms and novel breakthroughs in diagnostics and vaccines. Different technologies, such as the RT-PCR molecular test and the antigenic test, have been developed to identify subjects affected by the SARS-CoV-2 in order to improve the tracking of infection geographical diffusion. Novel rapid and highly sensitive diagnostic tests has been proposed for the detection of SARS-CoV-2 to improve the screening capability of suspected contagions. The strengthening of the vaccination campaign represents the most effective means to combat the SARS-CoV-2 infection and prevent severe manifestations of the virus—different classes of vaccines have been developed for this purpose. Further attention on the novel SARS-CoV-2 variant is necessary in order to verify the protection efficacy and virulence reduction of the infective agent in the recent vaccine campaign

Allergic diseases in the elderly: Biological characteristics and main immunological and non-immunological mechanisms

Life expectancy and the number of elderly people are progressively increasing around the world. Together with other pathologies, allergic diseases also show an increasing incidence in geriatric age. This is partly due to the growing emphasis on a more accurate and careful diagnosis of the molecular mechanisms that do not allow to ignore the real pathogenesis of many symptoms until now unknown, and partly to the fact that the allergic people from 20 years ago represent the elderly population now. Moreover, environmental pollution predisposes to the onset of allergic asthma and dermatitis which are the result of internal pathologies more than the expression of allergic manifestations. At the same time the food contamination permits the onset of allergic diseases related to food allergy. In this review we provide the state of the art on the physiological changes in the elderly responsible for allergic diseases, their biological characteristics and the major immunological and extra immunological mechanisms. Much emphasis is given to the management of several diseases in the elderly, including anaphylactic reactions. Moreover, some new features are discussed, such as management of asthma with the support of physical activity and the use of the AIT as prevention of respiratory diseases and for the purpose of a real and long lasting benefit. The mechanisms of adverse reactions to drugs are also discussed, due to their frequency in this age, especially in polytherapy regimens. Study of the modifications of the immune system is also of great importance, as regards to the distribution of the lymphocytes and also the presence of a chronic inflammatory disease related to the production of cytokines, especially in prevision of all the possible therapies to be adopted to allow an active and healthy aging

Meeting of the Advisory Committee on Immunization Practices (ACIP), January 27, 2021: summary minutes

Publication date from document properties.summary-2021-01.pdf2021981

Recent developments in the immunopathology of COVID-19

There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID-19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy of the COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID-19

Sensitization To A Milk Allergen Induces Differential Behavioral And Neurological Responses In Allergic C57BL/6J And BALB/cJ Mice

Studies have highlighted an association between food allergies and neuropsychiatric disorders such as anxiety, depression, and attention deficit hyperactivity disorder. Though the precise mechanism behind this relationship is unknown, it marks a potential novel therapeutic strategy outside of traditional neuropharmacological intervention. Food allergy is a heterogeneous disorder of the immune system characterized by an immune response that occurs reproducibly to a given food. Chronic allergen exposure in patients with mild or non-anaphylactic food allergies may cause or exacerbate psychiatric conditions. However, the variability in food allergies due to factors like genetic background introduces selection bias for individuals with overt anaphylactic reactions. To elucidate the framework of a mechanism by which peripheral non-anaphylactic food allergies cause behavioral changes, we sensitized mice to the cow’s milk allergen β-lactoglobulin (BLG). This dissertation consists of three studies to characterize the behavioral effects of mild cow’s milk allergy (CMA) and the underlying mechanism. The first study was to profile the behavioral symptoms of mice following sensitization to BLG and their underlying brain pathology. The second builds upon the findings of the first, to investigate changes in the brain using RNA sequencing and further histological analysis to understand what is happening in the brains of allergic mice. The third study compares two strains of mice with different genetic backgrounds and their responses to allergic sensitization. We evaluate the difference in their clinical symptoms, behavior, microbiomes, and released immune mediators in response to allergic challenge to investigate how genetic predisposition influences the effects we observed in our model. In study 1, male C57BL/6J mice sensitized to BLG presented increased anxiety-like behavior in the elevated-zero maze and grooming behavior tests and depression-like behavior during the tail-suspension test 24-48 hrs following allergic challenge. Since the mice sensitized to BLG were confirmed to be allergic based upon the abundance of BLG-specific IgE and IgG1, we histologically analyzed their intestines as the primary site of insult for CMA. In the ileum region of the small intestine, we observed a decrease in the tight junction protein occludin in BLG sensitized mice. A decrease in the abundance of occludin is common in intestinal inflammation and often leads to dysfunction of normal gut barrier function. Knowing male mice sensitized to BLG had a behavioral change, gut pathology, and were confirmed allergic, we then looked for evidence of brain pathology. We evaluated the status of astrocytes within the brain by staining for their structural protein glial fibrillary acidic protein (GFAP). We found that astrocytes in the substantia nigra were hypertrophic, and there was evidence of perivascular glial scarring which is common in neuroinflammatory conditions. The perivascular scarring also coincided with increased abundance of the proinflammatory cytokine, tumor necrosis factor-alpha (TNFα), which astrocytes both respond to and produce when activated. Together these data suggest CMA leads to anxiety and depression-like behavior in male mice and that the astrocyte response and signaling of cytokines like TNFα are involved in these behavioral changes. In the second study, we investigate region transcriptional profiles of BLG sensitized C57BL/6J male mice. Across the multiple brain regions, using ingenuity pathway analysis, we found pathways involved in inflammatory signaling, neuronal signaling, cell structural pathways, and disease states differentially activated in BLG sensitized mice. We validated some of our findings histologically using myelin basic protein (MBP) and IgG as targets based upon our previous glial findings and pathways involved in other glial cells and blood-brain barrier integrity. We observed no evidence of differential myelination through MBP in the brains of BLG sensitized mice but increased extravascular IgG in the brain parenchyma. High amounts of IgG staining within the brain implies impairment of normal blood-brain barrier function, which coincides with our previous astrocyte data. In study 3, we compared the C57BL/6J and BALB/cJ strains because of their genetic differences in the allergy response. The differences were apparent when observing the overt anaphylactic response to BLG challenge; only the BALB/cJ mice showed significant clinical symptoms. However, both strains produced BLG-specific IgE in response to treatment, but only the BALB/cJ strain produced IgG antibodies. Despite the described differences, males of both strains demonstrated similar anxiety-like behavior though the changes were more pronounced in C57BL/6J mice. Knowing the differences in immune responses observed in these strains, we quantified the cytokines released into the plasma, finding increases in a Th2 cytokines interleukin (IL)-10, -13, and -21, in addition to various chemokines in male C57BL/6J mice, but no increases in male BALB/cJ mice. Based on the observed differences, we wanted to investigate the impact BLG-sensitization had on the microbiome. Both strains were found to have distinct profiles, and BLG-sensitization led to strain-specific changes in the microbiome. Despite vastly different microbiome profiles, when we performed brain-specific pathway analysis of the microbiomes, the two strains had similar activation states of serotonergic, dopaminergic, addiction pathways, and various neurodegenerative diseases