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1.
PLoS Genet ; 15(6): e1007721, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31199803

RESUMO

B-cell activation yields abundant cell death in parallel to clonal amplification and remodeling of immunoglobulin (Ig) genes by activation-induced deaminase (AID). AID promotes affinity maturation of Ig variable regions and class switch recombination (CSR) in mature B lymphocytes. In the IgH locus, these processes are under control of the 3' regulatory region (3'RR) super-enhancer, a region demonstrated in the mouse to be both transcribed and itself targeted by AID-mediated recombination. Alternatively to CSR, IgH deletions joining Sµ to "like-switch" DNA repeats that flank the 3' super-enhancer can thus accomplish so-called "locus suicide recombination" (LSR) in mouse B-cells. Using an optimized LSR-seq high throughput method, we now show that AID-mediated LSR is evolutionarily conserved and also actively occurs in humans, providing an activation-induced cell death pathway in multiple conditions of B-cell activation. LSR either focuses on the functional IgH allele or is bi-allelic, and its signature is mainly detected when LSR is ongoing while it vanishes from fully differentiated plasma cells or from "resting" blood memory B-cells. Highly diversified breakpoints are distributed either within the upstream (3'RR1) or downstream (3'RR2) copies of the IgH 3' super-enhancer and all conditions activating CSR in vitro also seem to trigger LSR although TLR ligation appeared the most efficient. Molecular analysis of breakpoints and junctions confirms that LSR is AID-dependent and reveals junctional sequences somehow similar to CSR junctions but with increased usage of microhomologies.


Assuntos
Linfócitos B/imunologia , Citidina Desaminase/genética , Região de Troca de Imunoglobulinas/genética , Imunoglobulinas/imunologia , Alelos , Animais , Diferenciação Celular/genética , Citidina Desaminase/imunologia , Marcação de Genes , Humanos , Região de Troca de Imunoglobulinas/imunologia , Tecido Linfoide/imunologia , Camundongos , Tonsila Palatina/imunologia , Tonsila Palatina/metabolismo , Plasmócitos/imunologia , Plasmócitos/metabolismo , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Sequências Reguladoras de Ácido Nucleico
2.
J Neuroinflammation ; 16(1): 111, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138214

RESUMO

BACKGROUND: In a subgroup of patients suffering from progressive multiple sclerosis (MS), which is an inflammation-mediated neurodegenerative disease of the central nervous system (CNS), B cell aggregates were discovered within the meninges. Occurrence of these structures was associated with a more severe disease course and cortical histopathology. We have developed the B cell-dependent MP4-induced experimental autoimmune encephalomyelitis (EAE) as a mouse model to mimic this trait of the human disease. The aim of this study was to determine a potential role of lymphoid tissue inducer (LTi) and TH17 cells in the process of B cell aggregate formation in the MP4 model. METHODS: We performed flow cytometry of cerebellar and splenic tissue of MP4-immunized mice in the acute and chronic stage of the disease to analyze the presence of CD3-CD5-CD4+RORγt+ LTi and CD3+CD5+CD4+RORγt+ TH17 cells. Myelin oligodendrocyte glycoprotein (MOG):35-55-induced EAE was used as B cell-independent control model. We further determined the gene expression profile of B cell aggregates using laser capture microdissection, followed by RNA sequencing. RESULTS: While we were able to detect LTi cells in the embryonic spleen and adult intestine, which served as positive controls, there was no evidence for the existence of such a population in acute or chronic EAE in neither of the two models. Yet, we detected CD3-CD5-CD4-RORγt+ innate lymphoid cells (ILCs) and TH17 cells in the CNS, the latter especially in the chronic stage of MP4-induced EAE. Moreover, we observed a unique gene signature in CNS B cell aggregates compared to draining lymph nodes of MP4-immunized mice and to cerebellum as well as draining lymph nodes of mice with MOG:35-55-induced EAE. CONCLUSION: The absence of LTi cells in the cerebellum suggests that other cells might take over the function as an initiator of lymphoid tissue formation in the CNS. Overall, the development of ectopic lymphoid organs is a complex process based on an interplay between several molecules and signals. Here, we propose some potential candidates, which might be involved in the formation of B cell aggregates in the CNS of MP4-immunized mice.


Assuntos
Linfócitos B/imunologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Tecido Linfoide/imunologia , Esclerose Múltipla/imunologia , Células Th17/imunologia , Animais , Linfócitos B/patologia , Agregação Celular/imunologia , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/patologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Imunidade Inata/imunologia , Tecido Linfoide/patologia , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/patologia , Gravidez , Células Th17/patologia
3.
Vet Immunol Immunopathol ; 211: 44-48, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31084893

RESUMO

Regulatory B cells that produce IL-10 are now recognized as an important component of the immune system. We previously confirmed that IL-10 secreting CD21+ regulatory B cells (Breg cells) were present in ovine jejunal Peyer's patches (JPP) and this IL-10 production suppressed IL-12 and IFN-γ secretion. It is not known, however, whether ovine Breg cells are restricted to JPP or are present in other lymphoid tissues. Therefore, CD21+ B cells were purified from sheep JPP and from a variety of mucosal and systemic lymphoid tissues using magnetic cell sorting. Purified CD21+ B cells were stimulated with a TLR9-agonist, CpG oligodeoxynucleotide (CpG ODN), and the frequency of spontaneous and inducible (i) IL-10-secreting B cells was evaluated by ELISPOT. Spontaneous IL-10 secreting CD21+ B cells were present in mucosal (jejunal PP, parabronchial lymph nodes (LN), mesesnteric LN, and palatine tonsils) and systemic (spleen and blood) lymphoid tissues. Mucosal lymphoid tissues (parabronchial and mesenteric LNs and JPP) had the highest frequency of cells spontaneously secreting IL-10 while tonsils had the lowest. The frequency of B cells spontaneously secreting IL-10 was lowest in blood and spleen. There was large inter-animal variation in the frequency of CD21+ B cells spontaneously secreting IL-10 and no significant difference was detected following CpG ODN stimulation. When comparing within individual animals there was, however, a consistent increase in the frequency of CD21+ cells secreting IL-10 following CpG ODN stimulation versus stimulation with GpC control ODN. The presence of inducible (i)Breg cells in ovine mucosal tissues supports previous evidence from mice indicating that B cells have the capacity to modulate inflammatory responses. The presence of iBreg cells in ruminants may also provide a novel therapeutic target for both immunomodulatory drugs and vaccines designed to control antigen-specific mucosal inflammation.


Assuntos
Linfócitos B Reguladores/imunologia , Tecido Linfoide/citologia , Ovinos/imunologia , Animais , Linfócitos B Reguladores/efeitos dos fármacos , Linfócitos B Reguladores/fisiologia , ELISPOT/veterinária , Feminino , Citometria de Fluxo/veterinária , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Linfonodos/citologia , Linfonodos/imunologia , Tecido Linfoide/imunologia , Masculino , Mesentério/citologia , Mesentério/imunologia , Oligodesoxirribonucleotídeos/farmacologia , Baço/citologia , Baço/imunologia
4.
Int J Mol Sci ; 20(9)2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035605

RESUMO

Dual specificity phosphatases (DUSPs) have a well-known role as regulators of the immune response through the modulation of mitogen-activated protein kinases (MAPKs). Yet the precise interplay between the various members of the DUSP family with protein kinases is not well understood. Recent multi-omics studies characterizing the transcriptomes and proteomes of immune cells have provided snapshots of molecular mechanisms underlying innate immune response in unprecedented detail. In this study, we focus on deciphering the interplay between members of the DUSP family with protein kinases in immune cells using publicly available omics datasets. Our analysis resulted in the identification of potential DUSP-mediated hub proteins including MAPK7, MAPK8, AURKA, and IGF1R. Furthermore, we analyzed the association of DUSP expression with TLR4 signaling and identified VEGF, FGFR, and SCF-KIT pathway modules to be regulated by the activation of TLR4 signaling. Finally, we identified several important kinases including LRRK2, MAPK8, and cyclin-dependent kinases as potential DUSP-mediated hubs in TLR4 signaling. The findings from this study have the potential to aid in the understanding of DUSP signaling in the context of innate immunity. Further, this will promote the development of therapeutic modalities for disorders with aberrant DUSP signaling.


Assuntos
Fosfatases de Especificidade Dupla/metabolismo , Imunomodulação , Proteínas Quinases/metabolismo , Transdução de Sinais , Animais , Evolução Biológica , Células Sanguíneas/metabolismo , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Tecido Linfoide/citologia , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Camundongos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteoma , Proteômica/métodos
5.
Geroscience ; 41(2): 155-163, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31069636

RESUMO

In both mice and humans, the CD8 T cell compartment is expanded with age in the presence of a cytomegalovirus (CMV) infection due to an absolute increase in the CD8+ T cell effector memory (TEM) cells. It has been hypothesized that in CMV+ subjects, such accumulated TEM cells could interfere with responses to new infection by competing for space/resources or could inhibit new responses by other, undefined, means. Here we present evidence against this hypothesis. We show that MCMV-specific CD8 T cells accumulate in blood and bone marrow, but not lymph nodes (frequent sites of immune response initiation), in either persistent lifelong CMV infection or following reactivation. Moreover, adoptive transfer of effector memory T cells from MCMV positive mice into naïve animals did not interfere with either humoral or cellular response to West Nile virus or Listeria monocytogenes infection in recipient mice. We conclude that MCMV infection is unlikely to inhibit new immune responses in old animals through direct interference of MCMV-specific CD8 T cells with the priming.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Memória Imunológica , Tecido Linfoide/patologia , Transferência Adotiva , Animais , Linfócitos T CD8-Positivos/metabolismo , Citomegalovirus/imunologia , Modelos Animais de Doenças , Humanos , Tecido Linfoide/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Sensibilidade e Especificidade , Estatísticas não Paramétricas
6.
J Immunol ; 202(9): 2519-2526, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31010841

RESUMO

Inducible bronchus-associated lymphoid tissue (iBALT) is a tertiary lymphoid structure that resembles secondary lymphoid organs. iBALT is induced in the lung in response to Ag exposure. In some cases, such as infection with Mycobacterium tuberculosis, the formation of iBALT structure is indicative of an effective protective immune response. However, with persistent exposure to Ags during chronic inflammation, allergy, or autoimmune diseases, iBALT may be associated with exacerbation of inflammation. iBALT is characterized by well-organized T and B areas enmeshed with conventional dendritic cells, follicular dendritic cells, and stromal cells, usually located surrounding airways or blood vessels. Several of the molecular signals and cellular contributors that mediate formation of iBALT structures have been recently identified. This review will outline the recent findings associated with the formation and maintenance of iBALT and their contributions toward a protective or pathogenic function in pulmonary disease outcome.


Assuntos
Brônquios/imunologia , Células Dendríticas Foliculares/imunologia , Células Dendríticas/imunologia , Imunidade nas Mucosas , Pneumopatias/imunologia , Tecido Linfoide/imunologia , Animais , Brônquios/patologia , Células Dendríticas/patologia , Células Dendríticas Foliculares/patologia , Humanos , Pneumopatias/patologia , Tecido Linfoide/patologia
7.
Cancer Sci ; 110(6): 1853-1862, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30997706

RESUMO

The efficacy of preoperative neoadjuvant chemoradiotherapy (NAC) in cases of pancreatic cancer with extremely poor prognoses has been reported. In this study, we aimed to identify novel biomarkers that reflect prognoses following chemoradiotherapy using tertiary lymphoid organs (TLO) expressed in the tumor microenvironment. Resected tumor specimens were obtained from 140 pancreatic cancer patients. We retrospectively investigated the clinical relevance of TLO by categorizing patients into those who underwent upfront surgery (surgery first [SF]) and those who received NAC. The immunological elements within TLO were analyzed by immunohistochemistry (IHC). In the IHC analysis, the proportions of CD8+ T lymphocytes, PNAd+ high endothelial venules, CD163+ macrophages and Ki-67+ cells within the TLO were higher in the NAC group than in the SF group. In contrast, the proportion of programmed cell death-1+ immunosuppressive lymphocytes within TLO was lower in the NAC group than in the SF group. The NAC group demonstrated favorable prognoses compared with the SF group. In the multivariate analysis, the TLO/tumor ratio was determined as an independent predictive prognostic factor. In conclusion, the administration of preoperative chemoradiotherapy may influence the immunological elements in the tumor microenvironment and result in favorable prognoses in pancreatic ductal adenocarcinoma patients.


Assuntos
Carcinoma Ductal Pancreático/imunologia , Tecido Linfoide/imunologia , Neoplasias Pancreáticas/imunologia , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/terapia , Quimiorradioterapia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Tecido Linfoide/metabolismo , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos
8.
Immunol Rev ; 289(1): 31-41, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30977192

RESUMO

Lymphoid organs guarantee productive immune cell interactions through the establishment of distinct microenvironmental niches that are built by fibroblastic reticular cells (FRC). These specialized immune-interacting fibroblasts coordinate the migration and positioning of lymphoid and myeloid cells in lymphoid organs and provide essential survival and differentiation factors during homeostasis and immune activation. In this review, we will outline the current knowledge on FRC functions in secondary lymphoid organs such as lymph nodes, spleen and Peyer's patches and will discuss how FRCs contribute to the regulation of immune processes in fat-associated lymphoid clusters. Moreover, recent evidence indicates that FRC critically impact immune regulatory processes, for example, through cytokine deprivation during immune activation or through fostering the induction of regulatory T cells. Finally, we highlight how different FRC subsets integrate innate immunological signals and molecular cues from immune cells to fulfill their function as nexus between innate and adaptive immune responses.


Assuntos
Tecido Adiposo/imunologia , Fibroblastos/imunologia , Tecido Linfoide/imunologia , Células Estromais/imunologia , Linfócitos T Reguladores/imunologia , Imunidade Adaptativa , Animais , Homeostase , Humanos , Imunidade Inata , Imunomodulação , Ativação Linfocitária
9.
Immunol Rev ; 289(1): 115-128, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30977200

RESUMO

The initiation of T lymphocyte responses within secondary lymphoid organs involves interactions with different subsets of dendritic cells (DCs). Recent studies have revealed the complexity of microanatomical organization within lymphoid organs. Exactly how T cells and DCs locate each other and the type of cellular interactions required for optimal priming of effector and memory T cell responses are beginning to be unraveled. Here we review advances in our understanding of how T cell priming is choreographed during infections, highlight the importance of cell positioning in this process and discuss how a spectrum of cellular interactions shapes T cell activation and differentiation.


Assuntos
Células Dendríticas/imunologia , Tecido Linfoide/imunologia , Linfócitos T/imunologia , Animais , Apresentação do Antígeno , Comunicação Celular , Diferenciação Celular , Movimento Celular , Humanos , Ativação Linfocitária
11.
PLoS One ; 14(4): e0214526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30934014

RESUMO

Bloodstream infection (BSI) is the major cause of mortality in acute lymphocytic leukemia (ALL). Causative pathogens in BSI originate from the gut microbiota due to an increase in intestinal permeability, a process known as bacterial translocation (BT). The gut microbiota in physiological conditions is controlled by a large number of immune cells as part of the gut-associated lymphoid tissue (GALT).The aim of the current study was to investigate the mechanism of bacterial translocation in leukemia by identifying and characterizing alterations in the GALT in leukemic mouse model. Our studies revealed a severe impairment of the GALT characterized by a loss of lymphatic cells in ALL, which eventually led to BSI. We identified differentially expressed genes in the intraepithelium and the lamina propria, which may contribute to BT and to the impairment of lymphocyte migration.


Assuntos
Translocação Bacteriana , Microbioma Gastrointestinal , Mucosa Intestinal/microbiologia , Tecido Linfoide/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Feminino , Perfilação da Expressão Gênica , Histonas/química , Humanos , Imunidade nas Mucosas , Linfócitos/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Domínios Proteicos , RNA Ribossômico 16S/genética , Análise de Sequência de RNA
12.
Bull Exp Biol Med ; 166(6): 714-718, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31020580

RESUMO

Specific features of neurological deficit and changes in the cellular composition of tracheal lymphoid structures during the immediate stage (day 1) of hemorrhagic stroke were studied in rats with various behavioral parameters. Modeling of hemorrhage in the left caudate nucleus of the brain was followed by the development of motor disturbances in the forelimb use asymmetry test and corner rotation paradigm. These animals preferred to use the left forelimb (ipsilateral to the side of hemorrhage) to lean on the cylinder wall. The frequency of using the right forelimb or both forelimbs was reduced under these conditions. The number of left-sided rotations increased, while the percentage of right-sided rotations decreased. The observed changes were accompanied by immune dysfunction. It was manifested in the depletion of lymphoid aggregates of the tracheal wall in lymphocytes and plasma cells. The severity of abnormal neurological symptoms and disturbances in immune homeostasis during the immediate stage of hemorrhagic stroke was greater in behaviorally passive rats than in active specimens.


Assuntos
Núcleo Caudado/fisiopatologia , Hemorragia Cerebral/fisiopatologia , Tecido Linfoide/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Traqueia/fisiopatologia , Animais , Comportamento Animal , Núcleo Caudado/imunologia , Núcleo Caudado/patologia , Hemorragia Cerebral/imunologia , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Lateralidade Funcional , Imunidade Inata , Contagem de Linfócitos , Linfócitos/imunologia , Linfócitos/patologia , Tecido Linfoide/imunologia , Tecido Linfoide/patologia , Masculino , Atividade Motora , Ratos , Ratos Wistar , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Traqueia/imunologia , Traqueia/patologia
13.
Viruses ; 11(3)2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893756

RESUMO

Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Recent discoveries have demonstrated that tissue-resident lymphocyte subsets, comprised of innate lymphoid cells (ILCs) and unconventional T cells, have vital roles in the initiation of primary antiviral responses. Via direct and indirect mechanisms, ILCs and unconventional T cell subsets play a critical role in the ability of the immune system to mount an effective antiviral response through potent early cytokine production. In this review, we will summarize the current knowledge of tissue-resident lymphocytes during initial viral infection and evaluate their redundant or nonredundant contributions to host protection or virus-induced pathology.


Assuntos
Imunidade Inata , Tecido Linfoide/citologia , Subpopulações de Linfócitos T/imunologia , Viroses/imunologia , Animais , Diferenciação Celular/imunologia , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Humanos , Tecido Linfoide/imunologia , Camundongos
14.
Vet Immunol Immunopathol ; 208: 1-5, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30712787

RESUMO

M cells play a pivotal role in the induction of immune responses within the mucosa-associated lymphoid tissues. M cells exist principally in the follicle-associated epithelium (FAE) of the isolated solitary lymphoid follicles as well as in the lymphoid follicles of nasopharynx-associated lymphoid tissue and gut associated lymphoid tissue (GALT). Through lymphatic cannulation it is possible to investigate local immune responses induced following nasal Ag delivery in sheep. Hence, identifying sheep M cell markers would allow the targeting of M cells to offset the problem of trans-epithelial Ag delivery associated with inducing mucosal immunity. Sheep cDNA from the tonsils of the oropharynx and nasopharynx was PCR amplified using Glycoprotein-2 (GP2)-specific primers and expressed as a poly-His-tagged recombinant sheep GP2 (56 kDa) in HEK293 cells. The recombinant GP2 protein was purified using Ni-NTA affinity chromatography and polyclonal serum against the protein was raised in rats. The antiserum recognized the recombinant sheep GP2 and purified rat IgG against GP2 stained M cells in sections of sheep tonsils from nasopharynx and oropharynx. M cells were found to be present in epithelium of the palatine tonsils (oropharynx), pharyngeal tonsils as well as tubal tonsils (nasopharynx). They were also present in the FAE of the scattered lymphoid follicles over the base of the nasopharynx. Thus, GP2 has been identified to be an important M cell marker of nasopharynx and oropharynx-associated lymphoid tissues in sheep.


Assuntos
Proteínas Ligadas por GPI/genética , Tecido Linfoide/imunologia , Nasofaringe/imunologia , Orofaringe/imunologia , Animais , Biomarcadores , Proteínas Ligadas por GPI/imunologia , Células HEK293 , Humanos , Imunidade nas Mucosas/imunologia , Tecido Linfoide/citologia , Nasofaringe/citologia , Orofaringe/citologia , Tonsila Palatina/citologia , Tonsila Palatina/imunologia , Ovinos/imunologia
15.
Immunity ; 50(2): 493-504.e7, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30737144

RESUMO

Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4+ regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, their respective draining lymph nodes (LNs) and spleen. In these tissues, we identified Treg cell subpopulations with distinct degrees of NLT phenotype. Subpopulation pseudotime ordering and gene kinetics were consistent in recruitment to skin and colon, yet the initial NLT-priming in LNs and the final stages of NLT functional adaptation reflected tissue-specific differences. Predicted kinetics were recapitulated using an in vivo melanoma-induction model, validating key regulators and receptors. Finally, we profiled human blood and NLT Treg and Tmem cells, and identified cross-mammalian conserved tissue signatures. In summary, we describe the relationship between Treg cell heterogeneity and recruitment to NLTs through the combined use of computational prediction and in vivo validation.


Assuntos
Adaptação Fisiológica/imunologia , Análise de Célula Única/métodos , Linfócitos T Reguladores/imunologia , Transcriptoma/imunologia , Adaptação Fisiológica/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/imunologia , Colo/imunologia , Colo/metabolismo , Humanos , Memória Imunológica/genética , Memória Imunológica/imunologia , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Camundongos Transgênicos , Neoplasias Experimentais/genética , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Pele/imunologia , Pele/metabolismo , Baço/imunologia , Baço/metabolismo , Linfócitos T Reguladores/metabolismo
16.
Clin Perinatol ; 46(1): 77-88, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30771821

RESUMO

Oropharyngeal administration of mother's own milk-placing drops of milk directly onto the neonate's oral mucosa-may serve to (ex utero) mimic the protective effects of amniotic fluid for the extremely low birth weight infant; providing protection against necrotizing enterocolitis. This article presents current evidence to support biological plausibility for the use of OroPharyngeal Therapy with Mother's Own Milk (OPT-MOM) as an immunomodulatory therapy; an adjunct to enteral feeds of mother's milk administered via a nasogastric or orogastric tube. Current methods and techniques are reviewed, published evidence to guide clinical practice will be presented, and controversies in practice will be addressed.


Assuntos
Colostro/imunologia , Citocinas/imunologia , Nutrição Enteral/métodos , Enterocolite Necrosante/prevenção & controle , Imunomodulação , Tecido Linfoide/imunologia , Leite Humano/imunologia , Orofaringe/imunologia , Líquido Amniótico , Enterocolite Necrosante/imunologia , Feminino , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro , Mães , Gravidez
17.
Fish Shellfish Immunol ; 87: 490-498, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30711492

RESUMO

The present study describes histochemical and immunohistochemical characteristics of the spiral valve and its associated lymphoid tissue (GALT) in the dogfish Scyliorhinus canicula. The mucosal surface of the spiral valve represents the first line of defense against pathogens coming from the external environment through food. Epithelial, mucus and immune cells play a key role in controlling the inflammatory response. Valve intestine of S. canicula had many folds lined by simple columnar cells and goblet cells, which later reacted positive to PAS, AB and AB-PAS, histochemical stains differentiated the different types of mucins; lectin histochemistry (PNA and WGA), detected neutral and acid mucins secreted that plays an important role in protection against invading pathogens. Integrin α5ß1 was expressed in enterocytes that line the valve's folds with greater marking in the apical part of the cells. Laminin was found on the apical side of the epithelium, in fibrillar and cellular elements of the lamina propria and in the muscularis mucosa. In the spiral valve gut-associated lymphoid tissue (GALT) has been studied. For the first time, massive leucocytes aggregates were identified by confocal immunofluorescence techniques, using the following antibodies: TLR2, S100, Langerin/CD207. Our results expand knowledge about Dogfish valve intestine giving important news in understanding comparative immunology.


Assuntos
Cação (Peixe)/imunologia , Intestinos/imunologia , Tecido Linfoide/imunologia , Animais , Cação (Peixe)/anatomia & histologia , Histocitoquímica/veterinária , Imuno-Histoquímica/veterinária , Microscopia Confocal/veterinária , Mucinas/metabolismo
18.
Gen Physiol Biophys ; 38(1): 91-100, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30657461

RESUMO

Pregnant Wistar rats were exposed to ethanol under chronic conditions using the gavage method to assess the complement activation and effects of oxidative stress on fetus lymphoid organs and liver. The effects were monitored on both the 10th (G10) and the 30th (G30) day of the offspring of alcoholic mother rats. Maternal ethanol caused a significant decrease in the glutathione level, whereas malondialdehyde and carbonyl levels increased in the liver and lymphoid tissues. Na+,K+-ATPase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase activities in these organs also decreased. Furthermore, complement C3 and C5 activities of G10 and G30 groups were significantly higher compared with those of the control group. In conclusion, the results demonstrated that alcohol was capable of triggering damage to the membranes of the liver and lymphoid tissues of G10 and G30 groups, and C3 and C5 contributed to the development of alcohol-induced fetal tissue injury.


Assuntos
Animais Recém-Nascidos/imunologia , Animais Recém-Nascidos/metabolismo , Ativação do Complemento/efeitos dos fármacos , Etanol/farmacologia , Tecido Linfoide/efeitos dos fármacos , Tecido Linfoide/metabolismo , Mães , Estresse Oxidativo , Animais , Antioxidantes , Etanol/efeitos adversos , Feminino , Doenças Fetais/induzido quimicamente , Doenças Fetais/imunologia , Doenças Fetais/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Tecido Linfoide/imunologia , Gravidez , Ratos , Ratos Wistar
19.
Dev Comp Immunol ; 92: 212-222, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30513304

RESUMO

The human olfactory system is a mucosal surface and a major portal of entry for respiratory and neurotropic pathogens into the body. Understanding how the human nasopharynx-associated lymphoid tissue (NALT) halts the progression of pathogens into the lower respiratory tract or the central nervous system is key for developing effective cures. Although traditionally mice have been used as the gold-standard model for the study of human nasal diseases, mouse models present important caveats due to major anatomical and functional differences of the human and murine olfactory system and NALT. We summarize the NALT anatomy of different animal groups that have thus far been used to study host-pathogen interactions at the olfactory mucosa and to test nasal vaccines. The goal of this review is to highlight the strengths and limitations of each animal model of nasal immunity and to identify the areas of research that require further investigation to advance human health.


Assuntos
/imunologia , Tecido Linfoide/imunologia , Nasofaringe/imunologia , Doenças Nasais/imunologia , Bulbo Olfatório/imunologia , Mucosa Olfatória/imunologia , Animais , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno , Humanos , Imunidade , Camundongos
20.
Fish Shellfish Immunol ; 84: 509-520, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30227257

RESUMO

This study investigates the development of lymphoid organs and mucosal tissues in larval and juvenile meagre, Argyrosomus regius. For this purpose, meagre larvae were reared from hatch to the juvenile stage, under mesocosm conditions at 18-19 °C, using standard feeding sequences with live prey and artificial food. The kidney was evident upon hatch and included a visible pronephros, with undifferentiated stem cells and excretory tubules at 1 dph (3.15 ±â€¯0.1 mm SL). The thymus was first detected 8 dph (4.49 ±â€¯0.39 mm SL) and was clearly visible 12 dph (5.69 ±â€¯0.76 mm SL), 33 dph (15.69 ±â€¯1.81 mm SL) an outer thymocytic zone and inner epithelial zone were visible. The spleen was present 12 dph, located between exocrine pancreas and intestine and by 26 dph (11.84 ±â€¯1.3 mm SL) consisted of a mass of sinusoids filled with red blood cells. Melanomacrophage centers were found 83 dph (66.25 ±â€¯4.35 mm SL) in the spleen. Between 14-15 dph (6.9 ±â€¯1.1 mm SL), goblet and rodlet cells appear in the gill and intestinal epithelium. The lymphoid organs, which appear in the order of pronephric kidney (1 dph), thymus (8 dph) and spleen (12 dph) remarkably increase in size during the post-flexion stage. While functional studies are needed to confirm the activity of the immune response, the morphology of the lymphoid organs suggest that meagre is not immuno-competent until 83 dph.


Assuntos
Tecido Linfoide/crescimento & desenvolvimento , Membrana Mucosa/crescimento & desenvolvimento , Perciformes/crescimento & desenvolvimento , Animais , Tecido Linfoide/imunologia , Membrana Mucosa/imunologia , Perciformes/imunologia
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