scholarly journals Interference of SARS-CoV-2 with the Homeostasis of Ventilation and Perfusion in the Lung

Author(s):  
Clemente F. Arias ◽  
Francisco J. Acosta ◽  
Federica Bertocchini ◽  
Cristina Fernández-Arias

A growing number of studies suggest that SARS-CoV-2 could interfere with homeostatic mechanisms in the lung but the implications of this possible interference have not been fully explored in the literature. In this work, we examine the consequences that can be drawn from this hypothesis according to currently available knowledge. We suggest that one such consequence is the potential disruption of normal ventilation and perfusion of lung regions that may be distant from the infection sites. Loss of ventilation might result in local alveolar hypoxia and contribute to hypoxemia, which in turn could trigger homeostatic responses that enhance blood oxygenation by redistributing pulmonary blood circulation. Sudden changes in perfusion might then lead to the development of hydrostatic edema and eventually to vascular remodeling and inflammation. Therefore, the immune response might not be the only source of the substantial inflammation observed in lung tissues of patients with severe COVID-19, as is often assumed in the literature. The balance between the homeostatic and the immune reaction in each patient could account for the observed heterogeneity of the clinical manifestations of COVID-19.

1970 ◽  
Vol 5 (4) ◽  
pp. 51-60
Author(s):  
José Henrique Pereira Pinto ◽  
Renan Lemos de Toledo ◽  
William do Prado Franquelo

RESUMOIntrodução: Alergia à Proteína do Leite de Vaca (APLV) é uma doença inflamatória secundária à reação imunológica contra uma ou mais proteínas do leite de vaca (LV) que afeta principalmente a faixa pediátrica. A real prevalência é discutida em muitos estudos. As manifestações clínicas dependem do tipo da resposta imunológica, ser IgE mediada ou não. Os sintomas se iniciam por volta dos 06 meses de vida e na maioria dos casos, esse processo alérgico regride, com o paciente desenvolvendo tolerância até a adolescência. Casuística: Relata-se um caso de um paciente do sexo masculino, apresentando desde os 6 meses de idade de anafilaxia e broncoespasmo. Nesta época foi levado em hospitais e ambulatórios sendo diagnosticado e tratado como asma apenas, porém sem sucesso. Aos 18 anos, em consulta com especialista foi diagnosticado com APLV, apesar da dieta de exclusão, apresentou diversas reações anafiláticas, devido a ingestão acidental do alérgeno. Discussão: O paciente iniciou os primeiros sintomas quando houve contato com LV e apresentou teste laboratorial com valores compatíveis a patologia. Segundo a literatura a prevalência de APLV cai para menos de 1% aos 6 anos de vida e está persistência pode estar associada a múltiplos fatores, no caso relatado, o paciente não apresentou tolerância até o presente momento. Conclusão: APLV é uma doença usualmente de criança em que, se estas não adquirirem tolerância, complicações podem perdurar indefinidamente. O Diagnóstico precoce e o manejo adequado desta condição, revela grande importância na qualidade de vida e na prevenção de anafilaxia.Palavras chave: Alergia, Proteína do leite de vaca, Anafilaxia. ABSTRACT Introduction: Allergy to cow's milk (CMPA) is an inflammatory disease Introduction: Allergy to cow's milk (CMPA) is an inflammatory disease secondary to immune response against one or more cow's milk proteins (LV) which primarily affects pediatric patients. The current prevalence is discussed in many studies. The clinical manifestations depend on the type of immune response, being IgE mediated or not. Symptoms start at about 06 months of life and in most cases, the allergic process subsides, and the patient develops tolerance through adolescence. Case Report: We report the case of a male patient, who was presenting, since his 06 months of age, anaphylaxis and bronchospasm. At that time he was taken into hospitals and clinics being diagnosed and treated as asthma, but without success. At 18, in consultation with expert was diagnosed with CMPA, and despite the exclusion diet, presented several anaphylactic reactions due to accidental ingestion of the allergen. Discussion: The patient began the first symptoms when there was contact with LV and presented laboratory test values compatible with the pathology. According to the literature the prevalence of CMPA drops to less than 1% to 6 years of life and this persistence can be associated with multiple factors, in our case, the patient did not develop tolerance to date. Conclusion: CMPA is usually a child disease but ,if they do not acquire tolerance, complications can last indefinitely. Early diagnosis and appropriate management of this condition, reveals a great deal on quality of life and prevention of anaphylaxis. Keywords: Allergy, Cow’s milk protein, Anaphylaxis. 


2021 ◽  
Vol 22 (9) ◽  
pp. 4980
Author(s):  
Inés Roger ◽  
Javier Milara ◽  
Paula Montero ◽  
Julio Cortijo

Pulmonary hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance (PVR), which leads to right ventricular failure and premature death. There are multiple clinical manifestations that can be grouped into five different types. Pulmonary artery remodeling is a common feature in pulmonary hypertension (PH) characterized by endothelial dysfunction and smooth muscle pulmonary artery cell proliferation. The current treatments for PH are limited to vasodilatory agents that do not stop the progression of the disease. Therefore, there is a need for new agents that inhibit pulmonary artery remodeling targeting the main genetic, molecular, and cellular processes involved in PH. Chronic inflammation contributes to pulmonary artery remodeling and PH, among other vascular disorders, and many inflammatory mediators signal through the JAK/STAT pathway. Recent evidence indicates that the JAK/STAT pathway is overactivated in the pulmonary arteries of patients with PH of different types. In addition, different profibrotic cytokines such as IL-6, IL-13, and IL-11 and growth factors such as PDGF, VEGF, and TGFβ1 are activators of the JAK/STAT pathway and inducers of pulmonary remodeling, thus participating in the development of PH. The understanding of the participation and modulation of the JAK/STAT pathway in PH could be an attractive strategy for developing future treatments. There have been no studies to date focused on the JAK/STAT pathway and PH. In this review, we focus on the analysis of the expression and distribution of different JAK/STAT isoforms in the pulmonary arteries of patients with different types of PH. Furthermore, molecular canonical and noncanonical JAK/STAT pathway transactivation will be discussed in the context of vascular remodeling and PH. The consequences of JAK/STAT activation for endothelial cells and pulmonary artery smooth muscle cells’ proliferation, migration, senescence, and transformation into mesenchymal/myofibroblast cells will be described and discussed, together with different promising drugs targeting the JAK/STAT pathway in vitro and in vivo.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marta Ferreira-Gomes ◽  
Andrey Kruglov ◽  
Pawel Durek ◽  
Frederik Heinrich ◽  
Caroline Tizian ◽  
...  

AbstractThe pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.


2008 ◽  
Vol 7 (5-2) ◽  
pp. 420-423
Author(s):  
A. V. Subbotin ◽  
V. A. Semyonov ◽  
I. Yu. Torshin ◽  
O. A. Gromova ◽  
Ye. V. Fyodorova ◽  
...  

Here, we propose a method of forecasting the development of the heavy forms of the tick-borne encephalitis using diagnostic tables. The method is based on evaluation of the patients with syndrome of endogenous intoxication using immunological and biochemical data along with evaluation of the clinical manifestations. We also propose an advanced form of the method that includes data based on the genotype of OAS1 — the gene, coding oligonucleotidesynthetase needed for immune response to RNA viruses. OAS1 genotype is an important risk factor since the differences in catalytic activity of OAS1 isoenzymes result in different susceptibility to the virus of the tick-borne encephalitis.


1982 ◽  
Vol 242 (1) ◽  
pp. G1-G8 ◽  
Author(s):  
W. O. Dobbins

This review is a brief survey of our knowledge of the immune functions of the gastrointestinal tract. The mucosal immunologic system is present at all epithelial surfaces that are in direct contact with the external environment, is largely independent of the systemic immune response, and is governed by antigenic stimuli at epithelial surfaces. The plasma cell population responsive to these antigens is found just below the epithelium, and the antibodies produced are transported to the epithelial surface by a unique process. Finally, the antibodies secreted are able to function even in the presence of proteolytic enzymes. Brief reviews of immunophysiology and immunomorphology of the gastrointestinal immune system are enclosed. The immune response of the gut is discussed in relation to immune regulation by helper and suppressor systems. Even though secretory immunity may be considered "old hat," several new aspects of this system are emphasized along with an overview of the system. The clinical manifestations and pathophysiology of the two major adult immunodeficiency syndromes are reviewed in order to emphasize normal immunophysiology. There is a brief discussion of food allergy. Future directions that may be appropriate for research in both systemic and mucosal immunology are discussed in the final section.


Author(s):  
Graham Cooke

Sepsis is a clinical syndrome defined by the presence of both infection and a systemic inflammatory response with or without organ damage. The pathogenesis of sepsis is complex and may differ according to the infecting microbe, the site of primary infection, and the host’s immunological and physiological status prior to infection. The term ‘systemic inflammatory response syndrome’ refers to the clinical manifestations of a dysregulated host immune response, while ‘bacteraemia’, in contrast, refers to the presence of viable organisms that can be cultured from blood.


2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Karla Lucía F. Alvarez ◽  
Astrid Poma-Acevedo ◽  
Manolo Fernández-Díaz

Abstract Infectious coryza (IC), an upper respiratory tract disease affecting chickens, is caused by Avibacterium paragallinarum. The clinical manifestations of IC include nasal discharge, facial swelling, and lacrimation. This acute disease results in high morbidity and low mortality, while the course of the disease is prolonged and mortality rates are increased in cases with secondary infections. Studies regarding the immune response in infected chickens are scarce, and the local immune response is the focal point of investigation. However, a large body of work has demonstrated that severe infections can impact the systemic immune response. The objective of this study was to evaluate the systemic effects of Avibacterium paragallinarum (serovar B-1) infection on immune cells in specific pathogen-free (SPF) chickens. The current study revealed the presence of a transient circulating monocyte population endowed with high phagocytic ability and clear downregulation of major histocompatibility complex class II (MHC-II) surface expression. In human and mouse studies, this monocyte population (identified as tolerant monocytes) has been correlated with a dysfunctional immune response, increasing the risk of secondary infections and mortality. Consistent with this dysfunctional immune response, we demonstrate that B cells from infected chickens produced fewer antibodies than those from control chickens. Moreover, T cells isolated from the peripheral blood of infected chickens had a lower ability to proliferate in response to concanavalin A than those isolated from control chickens. These findings could be related to the severe clinical signs observed in complicated IC caused by the presence of secondary infections.


2007 ◽  
Vol 107 (5) ◽  
pp. 1023-1026 ◽  
Author(s):  
Changbin Shi ◽  
Robert Shenkar ◽  
H. Hunt Batjer ◽  
Irene J. Check ◽  
Issam A. Awad

Object Mechanisms of cerebral cavernous malformation (CCM) pathogenesis include genetic predisposition in some cases, but other factors are likely to be involved in lesion proliferation and clinical manifestations. Given the unique antigenic milieu of CCMs, there may be a characteristic immune response in these lesions. We hypothesize that the immunoglobulin (Ig) fraction in CCMs reflects an oligoclonal immune response not present in paired sera from the same patients or in other types of cerebrovascular malformations. Methods Surgically excised lesions from five patients with CCMs, three patients with arteriovenous malformations (AVMs), and four normal brain control specimens obtained at autopsy were homogenized and extract tested for IgG clonality by isoelectric focusing in parallel with each patient's serum. Results The authors detected B cells in all three lesions examined, and plasmacytes in two out of three lesions examined. Four of five extracts of homogenized CCMs showed an oligoclonal pattern of IgG distinct from the polyclonal pattern seen in those patients' sera. Immununoglobulin G oligoclonality was not seen in AVMs or control brain specimens. Conclusions The results of isoelectric focusing studies showed that CCM lesions had oligoclonal patterns of IgG unrelated to peripheral blood contamination, indicating selective synthesis of IgG within the lesions. This finding probably reflects a clonal expansion of B cells and/or plasmacytes in CCMs, an event that might be antigen-driven or a potential marker of inflammation.


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Christiane Maria Ayo ◽  
Márcia Machado de Oliveira Dalalio ◽  
Jeane Eliete Laguila Visentainer ◽  
Pâmela Guimarães Reis ◽  
Emília Ângela Sippert ◽  
...  

Chagas disease, which is caused by the flagellate parasiteTrypanosoma cruzi, affects 8–10 million people in Latin America. The disease is endemic and is characterised by acute and chronic phases that develop in the indeterminate, cardiac, and/or gastrointestinal forms. The immune response during humanT. cruziinfection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Polymorphisms in genes involved in the innate and specific immune response are being widely studied in order to clarify their possible role in the occurrence or severity of disease. Here we review the role of classic and nonclassic MHC,KIR, and cytokine host genetic factors on the infection byT. cruziand the clinical course of Chagas disease.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Yoh Zen ◽  
Yasuni Nakanuma

IgG4 cholangiopathy can involve any level of the biliary tree which exhibits sclerosing cholangitis or pseudotumorous hilar lesions. Most cases are associated with autoimmune pancreatitis, an important diagnostic clue. Without autoimmune pancreatitis, however, the diagnosis of IgG4-cholangiopathy is challenging. Indeed such cases have been treated surgically. IgG4-cholangiopathy should be diagnosed based on serological examinations including serum IgG4 concentrations, radiological features, and histological evidence of IgG4+plasma cell infiltration. Steroid therapy is very effective even at disease relapse. A Th2-dominant immune response or the activation of regulatory T cells seems to be involved in the underlying immune reaction. It is still unknown why IgG4 levels are specifically elevated in patients with this disease. IgG4 might be secondarily overexpressed by Th2 or regulatory cytokines given the lack of evidence that IgG4 is an autoantibody.


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