RESUMEN
A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells are required to explain how this remarkable system is energized and directed. I frame this article in terms of the major decisions that my colleagues and I have made in dendritic cell science and some of the guiding themes at the time the decisions were made. As a result of progress worldwide, there is now evidence of a central role for dendritic cells in initiating antigen-specific immunity and tolerance. The in vivo distribution and development of a previously unrecognized white cell lineage is better understood, as is the importance of dendritic cell maturation to link innate and adaptive immunity in response to many stimuli. Our current focus is on antigen uptake receptors on dendritic cells. These receptors enable experiments involving selective targeting of antigens in situ and new approaches to vaccine design in preclinical and clinical systems.
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Alergia e Inmunología/tendencias , Células Dendríticas/inmunología , Alergia e Inmunología/historia , Animales , Antígenos CD/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Diferenciación Celular/inmunología , Células Dendríticas/citología , Células Dendríticas/metabolismo , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Tolerancia Inmunológica/inmunología , Inmunidad Celular/inmunología , Lectinas Tipo C/metabolismo , Antígenos de Histocompatibilidad Menor , Modelos Animales , Receptores de Superficie Celular/metabolismo , Vacunas/inmunologíaRESUMEN
Cellular and humoral immunity to SARS-CoV-2 is critical to control primary infection and correlates with severity of disease. The role of SARS-CoV-2-specific T cell immunity, its relationship to antibodies, and pre-existing immunity against endemic coronaviruses (huCoV), which has been hypothesized to be protective, were investigated in 82 healthy donors (HDs), 204 recovered (RCs), and 92 active COVID-19 patients (ACs). ACs had high amounts of anti-SARS-CoV-2 nucleocapsid and spike IgG but lymphopenia and overall reduced antiviral T cell responses due to the inflammatory milieu, expression of inhibitory molecules (PD-1, Tim-3) as well as effector caspase-3, -7, and -8 activity in T cells. SARS-CoV-2-specific T cell immunity conferred by polyfunctional, mainly interferon-γ-secreting CD4+ T cells remained stable throughout convalescence, whereas humoral responses declined. Immune responses toward huCoV in RCs with mild disease and strong cellular SARS-CoV-2 T cell reactivity imply a protective role of pre-existing immunity against huCoV.
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Linfocitos T CD4-Positivos/inmunología , COVID-19/inmunología , Inmunidad Celular/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Femenino , Humanos , Inmunidad Humoral/inmunología , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Adulto JovenRESUMEN
Biologists, physicians and immunologists have contributed to the understanding of the cellular participants and biological pathways involved in inflammation. Here, we provide a general guide to the cellular and humoral contributors to inflammation as well as to the pathways that characterize inflammation in specific organs and tissues.
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Enfermedades Transmisibles/inmunología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Inflamación/inmunología , Enfermedad Aguda , Enfermedad Crónica , HumanosRESUMEN
Trafficking of tissue dendritic cells (DCs) via lymph is critical for the generation of cellular immune responses in draining lymph nodes (LNs). In the current study we found that DCs docked to the basolateral surface of lymphatic vessels and transited to the lumen through hyaluronan-mediated interactions with the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup-like structures. Furthermore, we show that targeted deletion of the gene Lyve1, antibody blockade or depletion of the DC hyaluronan coat not only delayed lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8+ T cell responses in skin-draining LNs. Our findings uncovered a previously unknown function for LYVE-1 and show that transit through the lymphatic network is initiated by the recognition of leukocyte-derived hyaluronan.
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Células Dendríticas/inmunología , Células Endoteliales/metabolismo , Glicoproteínas/genética , Ácido Hialurónico/metabolismo , Vasos Linfáticos/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animales , Movimiento Celular/inmunología , Células Dendríticas/metabolismo , Endotelio Linfático/citología , Endotelio Linfático/metabolismo , Citometría de Flujo , Glicoproteínas/metabolismo , Humanos , Inmunidad Celular/inmunología , Ganglios Linfáticos/inmunología , Proteínas de Transporte de Membrana , Ratones , Ratones Noqueados , Ratones Transgénicos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/inmunologíaRESUMEN
Human polyomaviruses cause a common childhood infection worldwide and typically elicit a neutralizing antibody and cellular immune response, while establishing a dormant infection in the kidney with minimal clinical manifestations. However, viral reactivation can cause severe pathology in immunocompromised individuals. We developed a high-throughput, functional antibody screen to examine the humoral response to BK polyomavirus. This approach enabled the isolation of antibodies from all peripheral B cell subsets and revealed the anti-BK virus antibody repertoire as clonally complex with respect to immunoglobulin sequences and isotypes (both IgM and IgG), including a high frequency of monoclonal antibodies that broadly neutralize BK virus subtypes and the related JC polyomavirus. Cryo-electron microscopy of a broadly neutralizing IgG single-chain variable fragment complexed with BK virus-like particles revealed the quaternary nature of a conserved viral epitope at the junction between capsid pentamers. These features unravel a potent modality for inhibiting polyomavirus infection in kidney transplant recipients and other immunocompromised patients.
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Anticuerpos Neutralizantes/inmunología , Linfocitos B/inmunología , Virus BK/inmunología , Memoria Inmunológica/inmunología , Virus JC/inmunología , Infecciones por Polyomavirus/inmunología , Poliomavirus/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Cápside/inmunología , Línea Celular , Epítopos/inmunología , Células HEK293 , Humanos , Inmunidad Celular/inmunología , Riñón/inmunologíaRESUMEN
The rapid changes in gene expression that accompany developmental transitions, stress responses and proliferation are controlled by signal-mediated coordination of transcriptional and post-transcriptional mechanisms. In recent years, understanding of the mechanics of these processes and the contexts in which they are employed during hematopoiesis and immune challenge has increased. An important aspect of this progress is recognition of the importance of RNA-binding proteins and noncoding RNAs. These have roles in the development and function of the immune system and in pathogen life cycles, and they represent an important aspect of intracellular immunity.
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Sistema Inmunológico/inmunología , Inmunidad Celular/genética , Activación de Linfocitos/genética , ARN Largo no Codificante/genética , ARN Pequeño no Traducido/genética , Animales , Expresión Génica/inmunología , Hematopoyesis/genética , Humanos , Inmunidad Celular/inmunología , Activación de Linfocitos/inmunología , Ratones , Procesamiento Postranscripcional del ARN/genética , Procesamiento Postranscripcional del ARN/inmunología , Proteínas de Unión al ARN/genética , Transducción de Señal/genética , Transcripción GenéticaRESUMEN
Immunological reactions are propelled by ever-changing signals that alter the translational ability of the RNA in the cells involved. Such alterations are considered to be consequential modifications in the transcriptomic decoding of the genetic blueprint. The identification of RNA-binding protein (RBP) assemblies engaged in the coordinative regulation of state-specific RNAs indicates alternative and exclusive means for determining the activation, plasticity and tolerance of cells of the immune system. Here we review current knowledge about RBP-regulated post-transcriptional events involved in the reactivity of cells of the immune system and the importance of their alteration during chronic inflammatory pathology and autoimmunity.
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Inmunidad Celular/genética , Procesamiento Postranscripcional del ARN , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo , Secuencias Reguladoras de Ácido Ribonucleico/genética , Animales , Autoinmunidad/genética , Autoinmunidad/inmunología , Humanos , Tolerancia Inmunológica/genética , Inmunidad Celular/inmunología , Inflamación/genética , Inflamación/inmunología , Activación de Linfocitos/genética , Activación de Linfocitos/inmunología , Linfopoyesis/genética , Linfopoyesis/inmunología , Ratones , Proteínas de Unión al ARN/genética , Secuencias Reguladoras de Ácido Ribonucleico/inmunología , Transducción de Señal/inmunologíaRESUMEN
Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXRα or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXRα-deficient mice. Our results demonstrate that signaling via LXRα in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets.
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Hematopoyesis/inmunología , Macrófagos/inmunología , Receptores Nucleares Huérfanos/inmunología , Bazo/inmunología , Animales , Benzoatos/farmacología , Bencilaminas/farmacología , Diferenciación Celular/inmunología , Citometría de Flujo , Inmunidad Celular/inmunología , Inmunohistoquímica , Receptores X del Hígado , Macrófagos/citología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Microscopía Fluorescente , Receptores Nucleares Huérfanos/agonistas , Transducción de Señal/inmunología , Organismos Libres de Patógenos Específicos , Bazo/citologíaRESUMEN
T cells are the key mediators in cell-mediated immunity. Their development and maturation involve a complex variety of interactions with nonlymphoid cell products and receptors. Highly specialized to defend against bacterial and viral infections, T cells also mediate immune surveillance against tumor cells and react to foreign tissues. T cell progenitors originate in the bone marrow and, through a series of defined and coordinated developmental stages, enter the thymus, differentiate, undergo selection, and eventually mature into functional T cells. The steps in this process are regulated through a complex transcriptional network, specific receptor-ligand pair interactions, and sensitization to trophic factors, which mediate the homing, proliferation, survival, and differentiation of developing T cells. This review examines the processes and pathways involved in the highly orchestrated development of T cell fate specification under physiological as well as pathological conditions.
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Inmunidad Celular/inmunología , Activación de Linfocitos/inmunología , Linfocitos T/inmunología , Linfocitos T/fisiología , Animales , Antígenos de Superficie/inmunología , Diferenciación Celular/inmunología , Linaje de la Célula , Quimiocinas/inmunología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatología , Receptores Notch/genética , Receptores Notch/metabolismo , Transducción de Señal/inmunología , Linfocitos T/citología , Timo/citología , Transcripción GenéticaRESUMEN
Changes in population density lead to phenotypic differentiation of solitary and gregarious locusts, which display different resistance to fungal pathogens; however, how to regulate their cellular immune strategies remains unknown. Here, our stochastic simulation of pathogen proliferation suggested that humoral defense always enhanced resistance to fungal pathogens, while phagocytosis sometimes reduced defense against pathogens. Further experimental data proved that gregarious locusts had significantly decreased phagocytosis of hemocytes compared to solitary locusts. Additionally, transcriptional analysis showed that gregarious locusts promoted immune effector expression (gnbp1 and dfp) and reduced phagocytic gene expression (eater) and the cytokine tumor necrosis factor (TNF). Interestingly, higher expression of the cytokine TNF in solitary locusts simultaneously promoted eater expression and inhibited gnbp1 and dfp expression. Moreover, inhibition of TNF increased the survival of solitary locusts, and injection of TNF decreased the survival of gregarious locusts after fungal infection. Therefore, our results indicate that the alerted expression of TNF regulated the immune strategy of locusts to adapt to environmental changes.
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Saltamontes/inmunología , Saltamontes/microbiología , Inmunidad Celular/inmunología , Metarhizium/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Animales , Expresión Génica/inmunología , Fagocitosis/inmunología , Densidad de Población , Transcripción Genética/inmunologíaRESUMEN
Dysregulated transforming growth factor TGF-ß signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-ß-dependent SMADs trafficking to the nucleus in vitro. The important in vivo role of IPO8 in pSMAD nuclear translocation was demonstrated by CRISPR/Cas9-mediated inactivation in zebrafish. Consistent with IPO8's role in BMP/TGF-ß signaling, ipo8-/- zebrafish presented mild to severe dorso-ventral patterning defects during early embryonic development. Moreover, ipo8-/- zebrafish displayed severe cardiovascular and skeletal defects that mirrored the human phenotype. Our work thus provides evidence that IPO8 plays a critical and non-redundant role in TGF-ß signaling during development and reinforces the existing link between TGF-ß signaling and connective tissue defects.
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Enfermedades Óseas/etiología , Enfermedades Cardiovasculares/etiología , Enfermedades del Tejido Conjuntivo/etiología , Inmunidad Celular/inmunología , Mutación con Pérdida de Función , Pérdida de Heterocigocidad , beta Carioferinas/genética , Adolescente , Adulto , Animales , Enfermedades Óseas/patología , Enfermedades Cardiovasculares/patología , Niño , Enfermedades del Tejido Conjuntivo/patología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Transducción de Señal , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Adulto Joven , Pez Cebra , beta Carioferinas/metabolismoRESUMEN
Mumps is a highly contagious viral disease that can be prevented by vaccination. In the last decade, we have encountered repeated outbreaks of mumps in highly vaccinated populations, which call into question the effectiveness of available vaccines. Animal models are crucial for understanding virus-host interactions, and viruses such as mumps virus (MuV), whose only natural host is the human, pose a particular challenge. In our study, we examined the interaction between MuV and the guinea pig. Our results present the first evidence that guinea pigs of the Hartley strain can be infected in vivo after intranasal and intratesticular inoculation. We observed a significant viral replication in infected tissues up to 5 days following infection and induction of cellular and humoral immune responses as well as histopathological changes in infected lungs and testicles, without clinical signs of disease. Transmission of the infection through direct contact between animals was not possible. Our results demonstrate that guinea pigs and guinea pig primary cell cultures represent a promising model for immunological and pathogenetic studies of the complex MuV infection. IMPORTANCE Understanding of mumps virus (MuV) pathogenesis and the immune responses against MuV infection is limited. One of the reasons is the lack of relevant animal models. This study explores the interaction between MuV and the guinea pig. We demonstrated that all tested guinea pig tissue homogenates and primary cell cultures are highly susceptible to MuV infection and that α2,3-sialylated glycans (MuV cellular receptors) are being abundantly expressed at their surface. The virus remains in the guinea pig lungs and trachea for up to 4 days following intranasal infection. Although asymptomatic, MuV infection strongly activates both humoral and cellular immune response in infected animals and provides protection against virus challenge. Infection of the lungs and testicles after intranasal and intratesticular inoculation, respectively, is also supported by histopathological changes in these organs. Our findings give perspective for application of guinea pigs in research on MuV pathogenesis, antiviral response, and vaccine development and testing.
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Virus de la Parotiditis , Paperas , Animales , Cobayas , Humanos , Paperas/inmunología , Paperas/fisiopatología , Paperas/virología , Virus de la Parotiditis/metabolismo , Replicación Viral , Células Cultivadas , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Pulmón/virología , Testículo/virologíaRESUMEN
Type-2-cell-mediated immunity, rich in eosinophils, basophils, mast cells, CD4(+) T helper 2 (Th2) cells, and type 2 innate lymphoid cells (ILC2s), protects the host from helminth infection but also drives chronic allergic diseases like asthma and atopic dermatitis. Barrier epithelial cells (ECs) represent the very first line of defense and express pattern recognition receptors to recognize type-2-cell-mediated immune insults like proteolytic allergens or helminths. These ECs mount a prototypical response made up of chemokines, innate cytokines such as interleukin-1 (IL-1), IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), as well as the alarmins uric acid, ATP, HMGB1, and S100 proteins. These signals program dendritic cells (DCs) to mount Th2-cell-mediated immunity and in so doing boost ILC2, basophil, and mast cell function. Here we review the general mechanisms of how different stimuli trigger type-2-cell-mediated immunity at mucosal barriers and how this leads to protection or disease.
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Células Epiteliales/inmunología , Helmintiasis/inmunología , Hipersensibilidad/inmunología , Inmunidad Celular/inmunología , Membrana Mucosa/inmunología , Animales , Quimiocinas/inmunología , Citocinas/inmunología , Células Dendríticas/inmunología , Humanos , Membrana Mucosa/parasitología , Células Th2/inmunología , Uniones Estrechas/inmunologíaRESUMEN
The ongoing arms race between hosts and microbes has fueled the evolution of novel strategies for diversifying the molecules involved in immune responses. Characterization of immune systems from an ever-broadening phylogenetic range of organisms reveals that there are many mechanisms by which this diversity can be generated and maintained. Diversification strategies operate at the level of populations, genomes, genes, and even individual transcripts. Lineage-specific innovations have been cataloged within the immune systems of both invertebrates and vertebrates. Furthermore, somatic diversification of immune receptor genes has now been described in jawless vertebrates and some invertebrate species. In addition to pathogen detection, immunological diversity plays important roles in several distinct allorecognition systems. In this Brief Review, we highlight some of the evolutionary innovations employed by a variety of metazoan species to generate the molecular diversity required to detect a vast array of molecules in the context of both immune response and self/nonself-recognition.
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Inmunidad Adaptativa/genética , Inmunidad Celular/genética , Invertebrados/inmunología , Receptores Inmunológicos/genética , Vertebrados/inmunología , Inmunidad Adaptativa/inmunología , Animales , Evolución Biológica , Evolución Molecular , Variación Genética/genética , Inmunidad Celular/inmunología , Invertebrados/genética , Receptores Inmunológicos/inmunología , Vertebrados/genéticaRESUMEN
CTLs are known to contribute to immunity toward Theileria parva, the causative agent of East Coast fever. The Tp967-75 CTL epitope from the Muguga strain of T. parva is polymorphic in other parasite strains. Identifying the amino acids important for MHC class I binding, as well as TCR recognition of epitopes, can allow the strategic selection of Ags to induce cellular immunity toward T. parva In this study, we characterized the amino acids important for MHC class I binding and TCR recognition in the Tp967-75 epitope using alanine scanning and a series of variant peptide sequences to probe these interactions. In a peptide-MHC class I binding assay, we found that the amino acids at positions 1, 2, and 3 were critical for binding to its restricting MHC class I molecule BoLA-1*023:01. With IFN-γ ELISPOT and peptide-MHC class I Tet staining assays on two parasite-specific bovine CTL lines, we showed that amino acids at positions 5-8 in the epitope were required for TCR recognition. Only two of eight naturally occurring polymorphic Tp9 epitopes were recognized by both CTLs. Finally, using a TCR avidity assay, we found that a higher TCR avidity was associated with a stronger functional response toward one of two variants recognized by the CTL. These data add to the growing knowledge on the cross-reactivity of epitope-specific CTLs and specificities that may be required in the selection of Ags in the design of a wide-spectrum vaccine for East Coast fever.
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Antígenos de Histocompatibilidad Clase I/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T Citotóxicos/inmunología , Theileria parva/inmunología , Theileriosis/inmunología , Secuencia de Aminoácidos , Animales , Antígenos de Protozoos/inmunología , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/parasitología , Línea Celular , Epítopos de Linfocito T/inmunología , Inmunidad Celular/inmunología , Theileriosis/parasitologíaRESUMEN
The latent viral reservoir is the critical barrier for the development of a cure for HIV-1 infection. Previous studies have shown direct antiviral activity of potent HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) administered when antiretroviral therapy (ART) was discontinued, but it remains unclear whether bNAbs can target the viral reservoir during ART. Here we show that administration of the V3 glycan-dependent bNAb PGT121 together with the Toll-like receptor 7 (TLR7) agonist vesatolimod (GS-9620) during ART delayed viral rebound following discontinuation of ART in simian-human immunodeficiency virus (SHIV)-SF162P3-infected rhesus monkeys in which ART was initiated during early acute infection. Moreover, in the subset of monkeys that were treated with both PGT121 and GS-9620 and that did not show viral rebound after discontinuation of ART, adoptive transfer studies and CD8-depletion studies also did not reveal virus. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy for targeting the viral reservoir.
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Anticuerpos Antivirales/inmunología , VIH-1/efectos de los fármacos , VIH-1/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/terapia , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Virus de la Inmunodeficiencia de los Simios/inmunología , Receptor Toll-Like 7/agonistas , Traslado Adoptivo , Animales , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Anticuerpos Neutralizantes/inmunología , Antígenos CD8/deficiencia , Antígenos CD8/inmunología , ADN Viral/análisis , Femenino , Anticuerpos Anti-VIH/inmunología , VIH-1/genética , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/inmunología , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/inmunología , Macaca mulatta/inmunología , Macaca mulatta/virología , Masculino , Pteridinas/farmacología , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/genética , Receptor Toll-Like 7/inmunología , Carga ViralRESUMEN
INTRODUCTION: To control the spread of severe disease caused by mutant strains of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is necessary to determine whether continued vaccination enhances humoral and cellular immunity. AIM: In this study, we examined the changes in humoral and cellular immunity to SARS-CoV-2 after administration of the third vaccination in Japanese adults who had received the second dose of messenger ribonucleic acid (mRNA)-1273 vaccine and the third vaccination (BNT162b2 or mRNA-1273). METHODS: We measured anti-spike antibodies in immunoglobulin G (IgG) and anti-nucleocapsid IgG titers in the serum of the vaccinated subjects. To evaluate cellular immunity, the peripheral blood mononuclear cells of inoculated individuals were cultured with spiked proteins, including those of the SARS-CoV-2 conventional strain and Omicron strain, and then subjected to enzyme-linked immunospot (ELISPOT). RESULTS: The results revealed that the anti-SARS-CoV-2 spike protein antibody titer increased after the third vaccination and was maintained; however, a decrease was observed at 6 months after vaccination. SARS-CoV-2 antigen-specific T helper (Th)1 and Th2 cell responses were also induced after the third vaccination and were maintained for 6 months after vaccination. Furthermore, induction of cellular immunity against Omicron strains by the omicron non-compliant vaccines, BNT162b2 or mRNA-1273, was observed. CONCLUSION: These findings demonstrate the effectiveness of vaccination against unknown mutant strains that may occur in the future and provide important insights into vaccination strategies.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Celular , Inmunidad Humoral , Inmunoglobulina G , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , COVID-19/inmunología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Inmunidad Humoral/inmunología , Inmunidad Celular/inmunología , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Glicoproteína de la Espiga del Coronavirus/inmunología , Masculino , Femenino , Persona de Mediana Edad , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Adulto , Anciano , Vacunación , Leucocitos Mononucleares/inmunología , Inmunización SecundariaRESUMEN
Vaccination is an essential public health measure for infectious disease prevention. The exposure of the immune system to vaccine formulations with the appropriate kinetics is critical for inducing protective immunity. In this work, faceted microneedle arrays were designed and fabricated utilizing a three-dimensional (3D)-printing technique called continuous liquid interface production (CLIP). The faceted microneedle design resulted in increased surface area as compared with the smooth square pyramidal design, ultimately leading to enhanced surface coating of model vaccine components (ovalbumin and CpG). Utilizing fluorescent tags and live-animal imaging, we evaluated in vivo cargo retention and bioavailability in mice as a function of route of delivery. Compared with subcutaneous bolus injection of the soluble components, microneedle transdermal delivery not only resulted in enhanced cargo retention in the skin but also improved immune cell activation in the draining lymph nodes. Furthermore, the microneedle vaccine induced a potent humoral immune response, with higher total IgG (Immunoglobulin G) and a more balanced IgG1/IgG2a repertoire and achieved dose sparing. Furthermore, it elicited T cell responses as characterized by functional cytotoxic CD8+ T cells and CD4+ T cells secreting Th1 (T helper type 1)-cytokines. Taken together, CLIP 3D-printed microneedles coated with vaccine components provide a useful platform for a noninvasive, self-applicable vaccination.
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Linfocitos T CD8-positivos/inmunología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Impresión Tridimensional/instrumentación , Vacunación/métodos , Vacunas/administración & dosificación , Administración Cutánea , Animales , Sistemas de Liberación de Medicamentos , Femenino , Ratones , Ratones Endogámicos C57BL , Ovalbúmina/inmunologíaRESUMEN
Despite mounting evidence implicating inflammation in cardiovascular diseases, attempts at clinical translation have shown mixed results. Recent preclinical studies have reenergized this field and provided new insights into how to favorably modulate cardiac macrophage function in the context of acute myocardial injury and chronic disease. In this review, we discuss the origins and roles of cardiac macrophage populations in the steady-state and diseased heart, focusing on the human heart and mouse models of ischemia, hypertensive heart disease, and aortic stenosis. Specific attention is given to delineating the roles of tissue-resident and recruited monocyte-derived macrophage subsets. We also highlight emerging concepts of monocyte plasticity and heterogeneity among monocyte-derived macrophages, describe possible mechanisms by which infiltrating monocytes acquire unique macrophage fates, and discuss the putative impact of these populations on cardiac remodeling. Finally, we discuss strategies to target inflammatory macrophage populations.
Asunto(s)
Insuficiencia Cardíaca/inmunología , Insuficiencia Cardíaca/terapia , Inmunidad Celular/inmunología , Inflamación/inmunología , Inflamación/terapia , Animales , Humanos , Macrófagos/inmunología , Monocitos/inmunología , Miocardio/inmunología , Miocardio/patologíaRESUMEN
BACKGROUND: The pathogenesis of migraine remains unclear; however, a large body of evidence supports the hypothesis that immunological mechanisms play a key role. Therefore, we aimed to review current studies on altered immunity in individuals with migraine during and outside attacks. METHODS: We searched the PubMed database to investigate immunological changes in patients with migraine. We then added other relevant articles on altered immunity in migraine to our search. RESULTS: Database screening identified 1,102 articles, of which 41 were selected. We added another 104 relevant articles. We found studies reporting elevated interictal levels of some proinflammatory cytokines, including IL-6 and TNF-α. Anti-inflammatory cytokines showed various findings, such as increased TGF-ß and decreased IL-10. Other changes in humoral immunity included increased levels of chemokines, adhesion molecules, and matrix metalloproteinases; activation of the complement system; and increased IgM and IgA. Changes in cellular immunity included an increase in T helper cells, decreased cytotoxic T cells, decreased regulatory T cells, and an increase in a subset of natural killer cells. A significant comorbidity of autoimmune and allergic diseases with migraine was observed. CONCLUSIONS: Our review summarizes the findings regarding altered humoral and cellular immunological findings in human migraine. We highlight the possible involvement of immunological mechanisms in the pathogenesis of migraine. However, further studies are needed to expand our knowledge of the exact role of immunological mechanisms in migraine pathogenesis.