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HNO Aug 2023Hyperplasia of the pharyngeal tonsils is to be considered pathologic when nasopharyngeal symptoms of mechanical obstruction and/or chronic inflammation occur. Chronic... (Review)
Review
Hyperplasia of the pharyngeal tonsils is to be considered pathologic when nasopharyngeal symptoms of mechanical obstruction and/or chronic inflammation occur. Chronic Eustachian tube dysfunction can result in various middle ear diseases such as conductive hearing loss, cholesteatoma, and recurrent acute otitis media. During examination, attention should be paid to the presence of adenoid facies (long face syndrome), with a permanently open mouth and visible tip of the tongue. In the case of severe symptoms and/or failure of conservative treatment, adenoidectomy is usually performed on an outpatient basis. Conventional curettage remains the established standard treatment in Germany. Histologic evaluation is indicated for clinical evidence of mucopolysaccharidoses. Due to the risk of hemorrhage, the preoperative bleeding questionnaire, which is obligatory before every pediatric surgery, is referred to. Recurrence of adenoids is possible despite correct adenoidectomy. Before discharge home, otorhinolaryngologic inspection of the nasopharynx for secondary bleeding should be performed and anesthesiologic clearance obtained.
Topics: Child; Humans; Adenoids; Adenoidectomy; Otitis Media; Inflammation; Hypertrophy; Otitis Media with Effusion
PubMed: 37491540
DOI: 10.1007/s00106-023-01299-6 -
Immunity Aug 2023Highly effective vaccines elicit specific, robust, and durable adaptive immune responses. To advance informed vaccine design, it is critical that we understand the...
Highly effective vaccines elicit specific, robust, and durable adaptive immune responses. To advance informed vaccine design, it is critical that we understand the cellular dynamics underlying responses to different antigen formats. Here, we sought to understand how antigen-specific B and T cells were activated and participated in adaptive immune responses within the mucosal site. Using a human tonsil organoid model, we tracked the differentiation and kinetics of the adaptive immune response to influenza vaccine and virus modalities. Each antigen format elicited distinct B and T cell responses, including differences in their magnitude, diversity, phenotype, function, and breadth. These differences culminated in substantial changes in the corresponding antibody response. A major source of antigen format-related variability was the ability to recruit naive vs. memory B and T cells to the response. These findings have important implications for vaccine design and the generation of protective immune responses in the upper respiratory tract.
Topics: Humans; Influenza Vaccines; Antibody Formation; Antibodies, Viral; T-Lymphocytes; Antigens; Organoids; Influenza, Human
PubMed: 37478854
DOI: 10.1016/j.immuni.2023.06.019 -
Cell Reports Jun 2023Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging...
Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and association with autoimmune disease. To better understand the structural basis of IL-21 signaling, we determine the structure of the IL-21-IL-21R-γc ternary signaling complex by X-ray crystallography and a structure of a dimer of trimeric complexes using cryo-electron microscopy. Guided by the structure, we design analogs of IL-21 by introducing substitutions to the IL-21-γc interface. These IL-21 analogs act as partial agonists that modulate downstream activation of pS6, pSTAT3, and pSTAT1. These analogs exhibit differential activity on T and B cell subsets and modulate antibody production in human tonsil organoids. These results clarify the structural basis of IL-21 signaling and offer a potential strategy for tunable manipulation of humoral immunity.
Topics: Humans; Cryoelectron Microscopy; Interleukins; Germinal Center; Crystallography, X-Ray; Interleukin-2
PubMed: 37339051
DOI: 10.1016/j.celrep.2023.112657 -
Immunity Feb 2024Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas...
Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.
Topics: Humans; Adult; Palatine Tonsil; B-Lymphocytes
PubMed: 38301653
DOI: 10.1016/j.immuni.2024.01.006 -
Nature Biotechnology Oct 2023In this study, we extended co-indexing of transcriptomes and epitopes (CITE) to the spatial dimension and demonstrated high-plex protein and whole transcriptome...
In this study, we extended co-indexing of transcriptomes and epitopes (CITE) to the spatial dimension and demonstrated high-plex protein and whole transcriptome co-mapping. We profiled 189 proteins and whole transcriptome in multiple mouse tissue types with spatial CITE sequencing and then further applied the method to measure 273 proteins and transcriptome in human tissues, revealing spatially distinct germinal center reactions in tonsil and early immune activation in skin at the Coronavirus Disease 2019 mRNA vaccine injection site.
Topics: Animals; Mice; Humans; Transcriptome; Epitopes; RNA, Messenger; Single-Cell Analysis; Gene Expression Profiling
PubMed: 36823353
DOI: 10.1038/s41587-023-01676-0