Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.
- MeSH
- COVID-19 * imunologie prevence a kontrola MeSH
- dospělí MeSH
- glykoprotein S, koronavirus imunologie MeSH
- humorální imunita MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutralizující protilátky * krev imunologie MeSH
- příjemce transplantátu * MeSH
- protilátky virové * krev imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- sekundární imunizace MeSH
- senioři MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 imunologie aplikace a dávkování MeSH
- vakcíny proti COVID-19 imunologie aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The use of nanoparticles as a delivery system for a specific antigen could solve many limitations of mucosal vaccine applications, such as low immunogenicity, or antigen protection and stabilization. In this study, we tested the ability of nasally administered chitosan nanoparticles loaded with glycoprotein B of murine cytomegalovirus to induce an immune response in an animal model. The choice of chitosan nanoparticle type was made by in vitro evaluation of sorption efficiency and antigen release. Three types of chitosan nanoparticles were prepared: crosslinked with tripolyphosphate, coated with hyaluronic acid, and in complex with polycaprolactone. The hydrodynamic size of the nanoparticles by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, stability, loading efficiency, and release kinetics with ovalbumin were evaluated. Balb/c mice were immunized intranasally using the three-dose protocol with nanoparticles, gB, and adjuvants Poly(I:C) and CpG ODN. Subsequently, the humoral and cell-mediated antigen-specific immune response was determined. On the basis of the properties of the tested nanoparticles, the cross-linked nanoparticles were considered optimal for further investigation. The results show that nanoparticles with Poly(I:C) and with gB alone raised IgG antibody levels above the negative control. In the case of mucosal IgA, only gB alone weakly induced the production of IgA antibodies compared to saline-immunized mice. The number of activated cells increased slightly in mice immunized with nanoparticles and gB compared to those immunized with gB alone or to negative control. The results demonstrated that chitosan nanoparticles could have potential in the development of mucosal vaccines.
- MeSH
- adjuvancia imunologická MeSH
- aplikace intranazální MeSH
- chitosan * chemie MeSH
- glykoproteiny MeSH
- imunizace MeSH
- imunoglobulin A MeSH
- Muromegalovirus * MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nanočástice * chemie MeSH
- slizniční imunita MeSH
- vakcíny * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Non-immune cells, like innate immune cells, can develop a memory-like phenotype in response to priming with microbial compounds or certain metabolites, which enables an enhanced response to a secondary unspecific stimulus. This paper describes a step-by-step protocol for the induction and analysis of trained immunity in human endothelial and smooth muscle cells. We then describe steps for cell culture with cryopreserved vascular cells, subcultivation, and induction of trained immunity. We then provide detailed procedures for downstream analysis using ELISA and qPCR. For complete details on the use and execution of this protocol, please refer to Sohrabi et al. (2020)1 and Shcnack et al.2.
- MeSH
- buněčné kultury MeSH
- ELISA MeSH
- endoteliální buňky * MeSH
- lidé MeSH
- myocyty hladké svaloviny MeSH
- trénovaná imunita * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Bakteriální lyzáty nespecificky stimulují celkovou imunitu organismu. Působí na nespecifické obranné mechanismy, což vede ke zvýšení IgA na sliznicích, fagocytární aktivitě a produkci interferonu gama. Mohou také stimulovat tvorbu specifických protilátek proti bakteriálním antigenům, které tvoří přípravek. V mnoha klinických studiích bylo prokázáno, že perorální bakteriální lyzáty snižují četnost opakovaných respiračních infekcí u dětí i dospělých a snižují potřebu podávání antibiotik.
Bacterial lysates stimulate the general immunity of the body in a non-specific way. They act on non-specific defense mechanisms, leading to an increase IgA in mucous membranes, phagocytic activity and interferon gamma production. They can also stimulate the production of specific antibodies against the bacterial antigens that make up the preparation. In many clinical trials, oral bacterial lysates have been shown to decrease the risk of recurrent respiratory infections in children and adults and reduce the need for antibiotics.
- Klíčová slova
- bakteriální lyzáty,
- MeSH
- adaptivní imunita účinky léků MeSH
- adjuvancia imunologická * aplikace a dávkování farmakologie terapeutické užití MeSH
- infekce dýchací soustavy imunologie patologie prevence a kontrola MeSH
- infekce močového ústrojí imunologie prevence a kontrola MeSH
- infekce reprodukčního traktu imunologie MeSH
- lidé MeSH
- přirozená imunita účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy.
- MeSH
- autoimunita * MeSH
- hojení ran * imunologie MeSH
- interleukin-6 * metabolismus imunologie MeSH
- lidé MeSH
- nádorové mikroprostředí * imunologie MeSH
- nádory * imunologie metabolismus patologie MeSH
- stárnutí * imunologie MeSH
- zánět * imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Intestinal epithelial cells have the capacity to upregulate MHCII molecules in response to certain epithelial-adhesive microbes, such as segmented filamentous bacteria (SFB). However, the mechanism regulating MHCII expression as well as the impact of epithelial MHCII-mediated antigen presentation on T cell responses targeting those microbes remains elusive. Here, we identify the cellular network that regulates MHCII expression on the intestinal epithelium in response to SFB. Since MHCII on the intestinal epithelium is dispensable for SFB-induced Th17 response, we explored other CD4+ T cell-based responses induced by SFB. We found that SFB drive the conversion of cognate CD4+ T cells to granzyme+ CD8α+ intraepithelial lymphocytes. These cells accumulate in small intestinal intraepithelial space in response to SFB. Yet, their accumulation is abrogated by the ablation of MHCII on the intestinal epithelium. Finally, we show that this mechanism is indispensable for the SFB-driven increase in the turnover of epithelial cells in the ileum. This study identifies a previously uncharacterized immune response to SFB, which is dependent on the epithelial MHCII function.
- MeSH
- adaptivní imunita fyziologie imunologie MeSH
- alergie klasifikace patofyziologie MeSH
- alveolární makrofágy fyziologie MeSH
- dýchací soustava * cytologie imunologie MeSH
- hlen fyziologie imunologie MeSH
- imunologické testy klasifikace MeSH
- infekce dýchací soustavy imunologie MeSH
- lidé MeSH
- lymfocyty fyziologie imunologie klasifikace MeSH
- přirozená imunita fyziologie imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Chronická rinosinusitida (CRS) je komplexní heterogenní zánětlivé onemocnění dutiny nosní a vedlejších dutin nosních, které velmi často vede ke snížení kvality života s následným socioekonomickým zatížením zdravotnictví. Klinicky se rozděluje na chronickou rinosinusitidu s polypy (CRSwNP) a chronickou rinosinusitidu bez polypů (CRSsNP). V současné době se výzkum zaměřuje na složení mikroflóry v jednotlivých částech lidského těla, které již pomohlo objasnit roli mikrobiomu u zánětlivých respiračních onemocnění, jako je asthma bronchiale a chronická obstrukční plicní nemoc (CHOPN). V této návaznosti se výzkumy zaměřují i na roli nosního mikrobiomu v možné iniciaci a potenciaci CRS. Zdravé nosní mikrobiologické prostředí je z velké části tvořeno bakteriemi, plísněmi a viry. Bližší poznání interakcí mezi mikroby a jednotlivými složkami imunitního systému mohou pomoci ozřejmit patofyziologické mechanizmy probíhající během CRS. V tomto přehledovém článku se zaměříme na současné poznatky o změnách a možné roli komplexního mikrobiomu horních cest dýchacích u CRS v porovnání se zdravým nosním prostředím.
Chronic rhinosinusitis (CRS) is a complex heterogeneous inflammatory disease of the nasal cavity and paranasal sinuses, which very often leads to a decrease in the quality of life with subsequent socioeconomic burden on health services and medical care. CRS is clinically divided into chronic rhinosinusitis with polyps (CRSwNP) and chronic rhinosinusitis without polyps (CRSsNP). Currently, research focuses on the composition of microflora in individual parts of the human body, which has already helped clarify the role of the microbiome in inflammatory respiratory diseases such as bronchial asthma and chronic obstructive pulmonary disease (COPD). Furthemore, research also focuses on the role of the nasal microbiome in possible initiation and potentiation of CRS. A healthy nasal microbiological environment is composed of bacteria, fungi, and viruses. A closer understanding of interactions between microbes and individual components of the immune system may help clarify the pathophysiological mechanisms involved during CRS. In this review article, we will focus on the current knowledge of composition changes and the possible role of the complex microbiome of the upper respiratory tract in CRS compared to a healthy nasal environment.
- MeSH
- chronická nemoc klasifikace MeSH
- lidé MeSH
- mikrobiota * imunologie MeSH
- nosní dutina mikrobiologie patofyziologie patologie MeSH
- nosní polypy diagnóza imunologie klasifikace MeSH
- rinosinusitida * diagnóza etiologie mikrobiologie patofyziologie MeSH
- slizniční imunita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
SARS-CoV-2 je virus, který infikuje respirační trakt a může způsobit závažné, někdy až život ohrožující onemocnění COVID-19. U více než 5 % symptomatických pacientů je infekce spojena s výskytem postakutních následků. První kontakt viru s imunitním systémem nazofaryngu a orofaryngu vyvolává slizniční imunitní odpověď spojenou s lokální produkcí sekrečních protilátek třídy imunoglobulinů A (sIgA), což může přispět k lokalizaci viru na horní cesty dýchací a asymptomatické či pouze klinicky mírné infekci. Během pandemie rychle vyvinuté systémově působící vakcíny úspěšně chrání před závažnou formou onemocnění a jeho postakutními následky, nicméně neindukují protilátky ve slizničních sekretech u dosud SARS-CoV-2-naivních jedinců. U těch, kteří již infekci prodělali, mohou přesto systémové vakcíny posílit tvorbu protilátek sIgA. Je třeba zdůraznit, že klinická prospěšnost systémové imunizace vakcínami proti COVID-19 přesvědčivě dokumentovaná u desítek milionů jedinců zastiňuje vzácné, mnohdy sporně dokumentované komplikace očkování. Neschopnost současných vakcín navodit slizniční imunitní odpověď a zabránit šíření viru sekrety infikovaných jedinců poukazuje na vzájemnou nezávislost slizniční a systémové imunity. To podtrhuje potřebu vývoje vakcín, které vyvolají patřičné odpovědi v obou kompartmentech imunitního systému.
SARS-CoV-2 is a virus which infects the respiratory tract and may cause severe, occasionally life-threatening disease COVID-19. In more than 5% of symptomatic patients the infection is associated with post-acute symptoms. The initial contact of the virus with the immune system of the nasopharynx and oropharynx induces a mucosal immune response manifested by the production of secretory IgA (sIgA) antibodies which may contribute to the restriction of the infection to the upper respiratory tract and an asymptomatic or clinically mild disease. The current systemically administered vaccines protected against the severe COVID-19 infection and its post-acute sequelae. However, they do not induce antibodies in mucosal secretions in SARS-CoV-2-naive individuals. In contrast, in those who previously experienced mucosal infection, systemically administered vaccines may stimulate sIgA production. The clinical benefit of systemic vaccination convincingly documented in tens of millions of individuals overshadows the rare, sometimes controversial reports of complications encountered after vaccination. The inability of current SARS-CoV-2 vaccines to induce mucosal immune responses and to prevent the spreading of the virus by external secretions demonstrates the mutual independence of mucosal and systemic compartments of the immune system, and thus emphasizes need for the development of vaccines inducing protective immune responses in both compartments.
- MeSH
- COVID-19 imunologie prevence a kontrola MeSH
- lidé MeSH
- slizniční imunita imunologie účinky léků MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The establishment of long-lasting immunity against pathogens is facilitated by the germinal center (GC) reaction, during which B cells increase their antibody affinity and differentiate into antibody-secreting cells (ASC) and memory cells. These events involve modifications in chromatin packaging that orchestrate the profound restructuring of gene expression networks that determine cell fate. While several chromatin remodelers were implicated in lymphocyte functions, less is known about SMARCA5. Here, using ribosomal pull-down for analyzing translated genes in GC B cells, coupled with functional experiments in mice, we identified SMARCA5 as a key chromatin remodeler in B cells. While the naive B cell compartment remained unaffected following conditional depletion of Smarca5, effective proliferation during B cell activation, immunoglobulin class switching, and as a result GC formation and ASC differentiation were impaired. Single-cell multiomic sequencing analyses revealed that SMARCA5 is crucial for facilitating the transcriptional modifications and genomic accessibility of genes that support B cell activation and differentiation. These findings offer novel insights into the functions of SMARCA5, which can be targeted in various human pathologies.
- MeSH
- adenosintrifosfatasy MeSH
- aktivace lymfocytů imunologie MeSH
- B-lymfocyty * metabolismus imunologie MeSH
- buněčná diferenciace * MeSH
- chromozomální proteiny, nehistonové * metabolismus genetika MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- přesmyk imunoglobulinových tříd genetika MeSH
- restrukturace chromatinu * MeSH
- zárodečné centrum lymfatické uzliny * imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
