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1.
Science ; 375(6576): 23-24, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34990255

RESUMEN

[Figure: see text].


Asunto(s)
Corazón , Linfocitos T , Tórax
2.
Cell Mol Life Sci ; 79(1): 61, 2022 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-34999972

RESUMEN

Apical localization of Intercellular Adhesion Receptor (ICAM)-1 regulates the adhesion and guidance of leukocytes across polarized epithelial barriers. Here, we investigate the molecular mechanisms that determine ICAM-1 localization into apical membrane domains of polarized hepatic epithelial cells, and their effect on lymphocyte-hepatic epithelial cell interaction. We had previously shown that segregation of ICAM-1 into apical membrane domains, which form bile canaliculi and bile ducts in hepatic epithelial cells, requires basolateral-to-apical transcytosis. Searching for protein machinery potentially involved in ICAM-1 polarization we found that the SNARE-associated protein plasmolipin (PLLP) is expressed in the subapical compartment of hepatic epithelial cells in vitro and in vivo. BioID analysis of ICAM-1 revealed proximal interaction between this adhesion receptor and PLLP. ICAM-1 colocalized and interacted with PLLP during the transcytosis of the receptor. PLLP gene editing and silencing increased the basolateral localization and reduced the apical confinement of ICAM-1 without affecting apicobasal polarity of hepatic epithelial cells, indicating that ICAM-1 transcytosis is specifically impaired in the absence of PLLP. Importantly, PLLP depletion was sufficient to increase T-cell adhesion to hepatic epithelial cells. Such an increase depended on the epithelial cell polarity and ICAM-1 expression, showing that the epithelial transcytotic machinery regulates the adhesion of lymphocytes to polarized epithelial cells. Our findings strongly suggest that the polarized intracellular transport of adhesion receptors constitutes a new regulatory layer of the epithelial inflammatory response.


Asunto(s)
Adhesión Celular/fisiología , Células Epiteliales/metabolismo , Hepatocitos/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Proteínas Proteolipídicas Asociadas a Mielina y Linfocito/metabolismo , Linfocitos T/metabolismo , Línea Celular Tumoral , Células Hep G2 , Humanos , Hígado/metabolismo , Proteínas Proteolipídicas Asociadas a Mielina y Linfocito/genética , Transcitosis/fisiología
3.
Handb Clin Neurol ; 184: 439-455, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35034753

RESUMEN

The notion that autoimmune responses to α-synuclein may be involved in the pathogenesis of this disorder stems from reports that mutations in α-synuclein or certain alleles of the major histocompatibility complex (MHC) are associated with the disease and that dopaminergic and norepinephrinergic neurons in the midbrain can present antigenic epitopes. Here, we discuss recent evidence that a defined set of peptides derived from α-synuclein act as antigenic epitopes displayed by specific MHC alleles and drive helper and cytotoxic T cell responses in patients with PD. Moreover, phosphorylated α-synuclein may activate T cell responses in a less restricted manner in PD. While the roles for the acquired immune system in disease pathogenesis remain unknown, preclinical animal models and in vitro studies indicate that T cells may interact with neurons and exert effects related to neuronal death and neuroprotection. These findings suggest that therapeutics that target T cells and ameliorate the incidence or disease severity of inflammatory bowel disorders or CNS autoimmune diseases such as multiple sclerosis may be useful in PD.


Asunto(s)
Enfermedad de Parkinson , alfa-Sinucleína , Animales , Dopamina , Humanos , Neuronas , Enfermedad de Parkinson/genética , Linfocitos T
4.
Leg Med (Tokyo) ; 54: 102007, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34973500

RESUMEN

Human herpes virus 6 (HHV-6) is one of the most important pathogens of viral myocarditis, and is often responsible for sudden death in young adults. A 59-year-old immunocompetent man died of serious lymphocytic myocarditis, and his peripheral blood sample showed HHV-6 DNAemia. Recently, HHV-6 cell entry and reactivation have been suggested to be regulated by the expression of specific CD receptors on T lymphocytes. Here, we report a case of HHV-6 myocarditis diagnosed using an experimental method focused on this unique cell tropism. The interaction between HHV-6 and CD expression was assessed using an immunofluorescence assay. Colocalization between HHV-6B and CD134 was detected in lymphocytes infiltrating the myocardium, which was highly suggestive of an active HHV-6B infection and could be a useful criterion for postmortem diagnosis of HHV-6B myocarditis in the acute phase.


Asunto(s)
Herpesvirus Humano 6 , Miocarditis , Herpesvirus Humano 6/genética , Humanos , Masculino , Persona de Mediana Edad , Miocarditis/diagnóstico , Linfocitos T , Tropismo
6.
BMC Genomics ; 23(1): 14, 2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-34991467

RESUMEN

BACKGROUND: Interferon regulatory factor-8 (IRF8) and nuclear factor-activated T cells c1 (NFATc1) are two transcription factors that have an important role in osteoclast differentiation. Thanks to ChIP-seq technology, scientists can now estimate potential genome-wide target genes of IRF8 and NFATc1. However, finding target genes that are consistently up-regulated or down-regulated across different studies is hard because it requires analysis of a large number of high-throughput expression studies from a comparable context. METHOD: We have developed a machine learning based method, called, Cohort-based TF target prediction system (cTAP) to overcome this problem. This method assumes that the pathway involving the transcription factors of interest is featured with multiple "functional groups" of marker genes pertaining to the concerned biological process. It uses two notions, Gene-Present Sufficiently (GP) and Gene-Absent Insufficiently (GA), in addition to log2 fold changes of differentially expressed genes for the prediction. Target prediction is made by applying multiple machine-learning models, which learn the patterns of GP and GA from log2 fold changes and four types of Z scores from the normalized cohort's gene expression data. The learned patterns are then associated with the putative transcription factor targets to identify genes that consistently exhibit Up/Down gene regulation patterns within the cohort. We applied this method to 11 publicly available GEO data sets related to osteoclastgenesis. RESULT: Our experiment identified a small number of Up/Down IRF8 and NFATc1 target genes as relevant to osteoclast differentiation. The machine learning models using GP and GA produced NFATc1 and IRF8 target genes different than simply using a log2 fold change alone. Our literature survey revealed that all predicted target genes have known roles in bone remodeling, specifically related to the immune system and osteoclast formation and functions, suggesting confidence and validity in our method. CONCLUSION: cTAP was motivated by recognizing that biologists tend to use Z score values present in data sets for the analysis. However, using cTAP effectively presupposes assembling a sizable cohort of gene expression data sets within a comparable context. As public gene expression data repositories grow, the need to use cohort-based analysis method like cTAP will become increasingly important.


Asunto(s)
Osteoclastos , Ligando RANK , Diferenciación Celular , Humanos , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/metabolismo , Aprendizaje Automático , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Ligando RANK/metabolismo , Linfocitos T/metabolismo
8.
Curr Microbiol ; 79(2): 44, 2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-34982235

RESUMEN

Hepatitis E contributes to 3.3 million acute hepatitis cases worldwide with 30% mortality in pregnant women. Pathogenesis of Hepatitis E is complex; thus, the present study was aimed at inflammasomes and associated cytokines in the immunopathogenesis of viral hepatitis E. PBMCs were isolated from 45 HEV IgM/HEV RNA-positive AVH/ALF and 19 healthy individuals and processed for mRNA expressions of NLRs, RLRs, and cytokines. PBMCs were cultured and stimulated with HEV-pORF-2 peptide in vitro for mRNA expression by RT-PCR and cytokines levels in serum/culture supernatant by ELISA. siRNA transfection and post-silencing effect in AVH PBMCs were also assessed by NLRP3 gene expression and IL-1ß and IL-18 levels by ELISA. The results demonstrated high viral load in ALF than AVH cases. mRNA expression of NLRP3 in AVH patients was found to be positively correlated with IL-18 (r = 0.74) and IL-1ß (r = 0.68); P < 0.0001***. Significant levels of serum IL-1ß and IL-18 cytokines were observed in AVH as compared to ALF patients. The levels of IL-1ß in the culture supernatant in mock and stimulated conditions were significantly higher in AVH than in ALF patients. Significant downregulation in NLRP3 gene expression was correlated with the reduced levels of IL-1ß and IL-18 cytokines in NLRP3-siRNA-transfected PBMCs. This study highlighted the significance of upregulated NLRP3 inflammasome leading to increased production of IL-18 and IL-1ß cytokines in sera of AVH patients. Thus, it indicated the role of Th1 response acting through the NLRP3 pathway which might have been helpful in the recovery of AVH patients. These promising results open multiple treatment avenues where specific inhibitors can be designed to modulate the progress of disease and its pathogenicity.


Asunto(s)
Hepatitis E , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Células Cultivadas , Citocinas/inmunología , Femenino , Hepatitis E/inmunología , Humanos , Inflamasomas/inmunología , Embarazo , Pronóstico , Linfocitos T/inmunología , Carga Viral
10.
Int J Immunogenet ; 49(1): 39-45, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34910357

RESUMEN

The ELISpot assay is a sensitive technique applied to assess cytokine-producing memory/effector T cells and human leukocyte antigens (HLA)-specific IgG-producing B cells. Besides the fact that the method is laborious and is difficult to standardise between laboratories, it may provide valuable information on the immune response of recipients before and after organ transplantation. In this article, we briefly review the recent literature and discuss the clinical significance of the ELISpot assay in predicting the risk and incidence of allograft rejection and survival.


Asunto(s)
Rechazo de Injerto , Trasplante de Riñón , Ensayo de Immunospot Ligado a Enzimas , Humanos , Interferón gamma , Linfocitos T
12.
Handb Exp Pharmacol ; 268: 297-310, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34173865

RESUMEN

Allergies are highly prevalent hypersensitivity responses to usually harmless substances. They are mediated by the immune system which causes pathologic responses such as type I (rhinoconjunctivitis, allergic asthma, atopy) or type IV hypersensitivity (allergic contact dermatitis). The different types of allergy are mediated by effector and memory T cells and, in the case of type I hypersensitivity, B cells. A prerequisite for the activation of these cells of the adaptive immune system is the activation of the innate immune system. The resulting inflammation is essential not only for the initiation but also for the elicitation and maintenance of allergies. Great progress has been made in the elucidation of the cellular and molecular pathomechanisms underlying allergen-induced inflammation. It is now recognized that the innate immune system in concert with tissue stress and damage responses orchestrates inflammation. This should enable the development of novel mechanism-based anti-inflammatory treatment strategies as well as of animal-free in vitro assays for the identification and potency classification of contact allergens.


Asunto(s)
Dermatitis Alérgica por Contacto , Inmunidad Innata , Alérgenos , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Dermatitis Alérgica por Contacto/etiología , Humanos , Inflamación , Linfocitos T
13.
Gene ; 806: 145921, 2022 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-34454033

RESUMEN

Maoto, a traditional Japanese medicine (Kampo), is widely used to treat upper respiratory tract infections, including influenza virus infection. Although maoto is known to inhibit pro-inflammatory responses in a rodent model of acute inflammation, its underlying mechanism remains to be determined. In this study, we investigated the involvement of immune responses and noradrenergic function in the inhibitory action of maoto. In a mouse model of polyI:C-induced acute inflammation, maoto was administered orally in conjunction with intraperitoneal injection of PolyI:C (6 mg/kg), and blood was collected after 2 h for measurement of plasma cytokines by ELISA. Maoto significantly decreased PolyI:C-induced TNF-α levels and increased IL-10 production. Neither pretreatment with IL-10 neutralizing antibodies nor T-cell deficiency using nude mice modified the inhibitory effect of maoto, indicating that the anti-inflammatory effects of maoto are independent of IL-10 and T cells. Furthermore, the inhibitory effects of maoto on PolyI:C-induced TNF-α production were not observed in ex vivo splenocytes, suggesting that maoto does not act directly on inflammatory cells. Lastly, pretreatment with a ß-adrenergic receptor antagonist partially cancelled the anti-inflammatory effects of maoto. Collectively, these results suggest that maoto mediates its anti-inflammatory effects via ß-adrenergic receptors in vivo.


Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Antiinflamatorios/farmacología , Inflamación/prevención & control , Interleucina-10/genética , Extractos Vegetales/farmacología , Receptores Adrenérgicos beta/genética , Administración Oral , Animales , Modelos Animales de Enfermedad , Efedrina/farmacología , Regulación de la Expresión Génica , Inyecciones Intraperitoneales , Interleucina-10/agonistas , Interleucina-10/inmunología , Japón , Masculino , Medicina Kampo/métodos , Ratones Endogámicos BALB C , Ratones Desnudos , Poli I-C/administración & dosificación , Poli I-C/antagonistas & inhibidores , Receptores Adrenérgicos beta/inmunología , Transducción de Señal , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/patología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
14.
J Clin Neurosci ; 95: 75-80, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34929655

RESUMEN

BACKGROUND: Interleukin 35 (IL-35) plays an anti-inflammatory in numerous autoimmune diseases. However, the potential roles of IL-35-producing T and B cells and serum IL-35 levels in the pathogenesis of myasthenia gravis (MG) and its association with disease activity in patients with MG remain unclear. METHODS: The percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells among peripheral blood mononuclear cells were determined in 37 patients with anti-acetylcholine receptor (AChR) antibody-positive MG and 35 healthy controls (HCs) by performing a flow cytometry analysis. Serum IL-35 levels in participants were determined using an enzyme-linked immunosorbent assay. Further, the correlations between IL35 levels and disease activity were analysed. RESULTS: The percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells were significantly lower in patients with anti-AChR antibody-positive MG than in HCs (p = 0.001 and p = 0.002, respectively). Furthermore, patients with thymoma and patients with generalized MG had lower percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells than those without thymoma and those with ocular MG (p = 0.001 and p = 0.003; p = 0.008 and p = 0.001, respectively). Interestingly, the suppression of IL-35 secretion correlated negatively with the activities of daily living scores of patients with MG (r = -0.4774, p = 0.0028) and the quantitative MG scores (r = -0.4656, p = 0.0037). The proportions of IL-35-producing T cells and B cells and serum levels of IL-35 increased after treatment. CONCLUSIONS: IL-35 may represent a potential biomarker for the clinical evaluation of MG.


Asunto(s)
Linfocitos B , Interleucinas , Leucocitos Mononucleares , Miastenia Gravis , Linfocitos T , Actividades Cotidianas , Autoanticuerpos , Linfocitos B/inmunología , Humanos , Receptores Colinérgicos , Linfocitos T/inmunología
15.
J Oncol Pharm Pract ; 28(1): 159-174, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34586003

RESUMEN

The most common adverse event associated with chimeric antigen receptor T-cell therapy is cytokine release syndrome, which is characterized by fever, hypoxia, and hypotension in varying degrees of severity. In severe cases, cytokine release syndrome can result in life-threatening symptoms such as multi-organ failure. The widely accepted first-line therapy for cytokine release syndrome management is tocilizumab with or without corticosteroids, but there is very limited guidance on the proper management of patients unresponsive to this regimen. There are emerging strategies that target cytokine release syndrome through novel mechanisms, showing promise in treating or preventing severe cytokine release syndrome. Although further clinical investigation is necessary to assess the applicability of the emerging approaches, these exploratory therapies may shape the future landscape of chimeric antigen receptor T-cell induced cytokine release syndrome management. This review article provides a comprehensive overview of the current and emerging therapies for the management of chimeric antigen receptor T-cell induced cytokine release syndrome, especially cases that are refractory to tocilizumab and steroids.


Asunto(s)
Receptores Quiméricos de Antígenos , Corticoesteroides , Síndrome de Liberación de Citoquinas , Humanos , Inmunoterapia Adoptiva , Linfocitos T
16.
Methods Mol Biol ; 2380: 165-174, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34802130

RESUMEN

Antibodies produced by plasma cells are a major arm of adaptive immunity. Germinal center reactions that include germinal center B cells and follicular T cells are fundamental players for antibody production, particularly antigen specific antibodies. Here we describe multiple methods that we and others have developed to analyze the production of antigen-specific antibodies in mice, with protocols for assessing antibody affinity and antibody isotype. The detection of antigen-specific IgE in serum using a traditional enzyme-linked immunosorbent assay (ELISA) method is often problematic due to much higher amounts of IgG. Thus we provide a specialized protocol for the detection of antigen-specific IgE in serum using ELISA.


Asunto(s)
Formación de Anticuerpos , Animales , Antígenos , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina E , Ratones , Linfocitos T
17.
Clin Nucl Med ; 47(1): e59-e60, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34034310

RESUMEN

ABSTRACT: We present a pediatric case with T-cell lymphoblastic leukemia and persistent chylothorax who was referred to lymphoscintigraphy to identify the site of leakage. Planar lymphoscintigraphy with SPECT/CT revealed hot spots at the left jugulovenous angle and the confluens of the vena brachiocephalica to vena cava, which were compatible with the sites of leakage. Hybrid imaging with SPECT/CT technique have great impact on accurate detection of the defects in the lymphatic system in patients with chylothorax.


Asunto(s)
Quilo , Quilotórax , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Quilotórax/diagnóstico por imagen , Humanos , Linfocintigrafia , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Linfocitos T
18.
Pharmacogenet Genomics ; 32(1): 10-15, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34320607

RESUMEN

OBJECTIVES: Nuclear factor of activated T cells C2 (NFATC2) is known as a member of the transcription family and enhances tumor necrosis factor-alpha (TNF-α) synthesis in human T cells at the gene transcription level. Although NFATC2 has a potential role in rheumatoid arthritis (RA) progression and treatment, no study has investigated the association between NFATC2 gene polymorphisms and response status in RA patients receiving TNF-α inhibitors. This study aimed to examine the effects of polymorphisms in NFATC2, a TNF-α transcription factor, on response to TNF-α inhibitors. METHODS: This prospective observational study was performed in two centers. Seven single nucleotide polymorphisms (SNPs) were investigated. Good responders were defined as patients with disease activity score (DAS)28 ≤3.2 after 6 months of treatment. Logistic regression analyses were used to investigate the association between genetic polymorphisms and response to the treatment. To test the model's goodness of fit, a Hosmer-Lemeshow test was performed. RESULTS: This study included 98 patients, among whom 46 showed favorable responses to the treatment. Patients with hypertension revealed an approximately three-fold lower response to TNF-α inhibitors compared to those without hypertension (23.5 vs. 76.5%; P = 0.049). After adjusting for covariates, C allele carriers of NFATC2 rs3787186 exhibited approximately three-fold lower rates of treatment response compared to those with TT genotype (P = 0.037). The Hosmer-Lemeshow test showed that the fitness of the multivariable analysis model was satisfactory (χ2 = 9.745; 8 degrees of freedom; P = 0.283). CONCLUSION: This study suggested an association between the C allele of rs3787186 and treatment response in RA patients receiving TNF-α inhibitors.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple/genética , Linfocitos T , Factor de Necrosis Tumoral alfa/genética
19.
Bioorg Chem ; 118: 105482, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34801946

RESUMEN

Podomycins A-L (1-12), 12 undescribed hypothemycin-type resorcylic acid lactones (RALs), were characterized from Podospora sp. G214, an endophyte harbored in the roots of Sanguisorba officinalis L. Their structures were addressed by spectroscopic data, X-ray crystallography, the modified Mosher's method, together with Mo2(OAc)4- and Rh2(OCOCF3)4-induced electronic circular dichroism (ICD) experiments. Podomycins A-C (1-3) represent the first class of natural RALs with a 13-membered macrolactone ring, while 4-12 are rearranged methoxycarbonyl substituted RALs. Biologically, compounds 2, 6, 8, 10, and 12 displayed immunosuppressive activities against T cell proliferation with IC50 values of 14.5-21.9 µM, and B cell proliferation with IC50 values of 22.3-36.5 µM, respectively. Further mechanism of action research demonstrated that podomycin F (6) distinctly induced apoptosis in activated T cells via MAPKs/AKT pathway.


Asunto(s)
Apoptosis/efectos de los fármacos , Inmunosupresores/farmacología , Lactonas/farmacología , Podospora/química , Linfocitos T/efectos de los fármacos , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inmunosupresores/química , Inmunosupresores/aislamiento & purificación , Lactonas/química , Lactonas/aislamiento & purificación , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Proteínas Proto-Oncogénicas c-akt , Relación Estructura-Actividad , Linfocitos T/metabolismo
20.
J Exp Med ; 219(2)2022 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-34914824

RESUMEN

In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRß repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.


Asunto(s)
COVID-19/complicaciones , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Interferón gamma/metabolismo , Células Asesinas Naturales/inmunología , Monocitos/metabolismo , Receptores de IgG/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Linfocitos T/inmunología , Adolescente , Células Epiteliales Alveolares/patología , Linfocitos B/inmunología , Vasos Sanguíneos/patología , COVID-19/inmunología , COVID-19/patología , Proliferación Celular , Niño , Estudios de Cohortes , Activación de Complemento , Citocinas/metabolismo , Enterocitos/patología , Femenino , Humanos , Inmunidad Humoral , Inflamación/patología , Interferón Tipo I/metabolismo , Interleucina-15/metabolismo , Activación de Linfocitos/inmunología , Masculino , Receptores de Antígenos de Linfocitos T/metabolismo , SARS-CoV-2/inmunología , Superantígenos/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/patología
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