Hypoplastic myelodysplastic syndrome (hMDS) and aplastic anemia (AA) are rare hematopoietic disorders characterized by pancytopenia with hypoplastic bone marrow (BM). hMDS and idiopathic AA share overlapping clinicopathological features, making a diagnosis very difficult. The differential diagnosis is mainly based on the presence of dysgranulopoiesis, dysmegakaryocytopoiesis, an increased percentage of blasts, and abnormal karyotype, all favouring the diagnosis of hMDS. An accurate diagnosis has important clinical implications, as the prognosis and treatment can be quite different for these diseases. Patients with hMDS have a greater risk of neoplastic progression, a shorter survival time and a lower response to immunosuppressive therapy compared with patients with AA. There is compelling evidence that these distinct clinical entities share a common pathophysiology based on the damage of hematopoietic stem and progenitor cells (HSPCs) by cytotoxic T cells. Expanded T cells overproduce proinflammatory cytokines (interferon‐γ and tumor necrosis factor‐α), resulting in decreased proliferation and increased apoptosis of HSPCs. The antigens that trigger this abnormal immune response are not known, but potential candidates have been suggested, including Wilms tumor protein 1 and human leukocyte antigen class I molecules. Our understanding of the molecular pathogenesis of these BM failure syndromes has been improved by next‐generation sequencing, which has enabled the identification of a large spectrum of mutations. It has also brought new challenges, such as the interpretation of variants of uncertain significance and clonal hematopoiesis of indeterminate potential. The present review discusses the main clinicopathological differences between hMDS and acquired AA, focuses on the molecular background and highlights the importance of molecular testing.
- MeSH
- autoimunitní hemolytická anemie etiologie genetika MeSH
- imunita genetika imunologie MeSH
- lidé MeSH
- myelodysplasticko-myeloproliferativní nemoci etiologie genetika MeSH
- prognóza MeSH
- syndromy selhání kostní dřeně etiologie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Okrem nedávnej pandémie COVID-19 bojueme aj s pandémiou nedostatku mikroživín, najmä deficitom vitamínu D. V súčasnosti nedostatok vitamínu D sa vyskytuje u takmer 80% populácie, najmä u marginalizovaných skupin. Doterajšie poznatky z obdobia pandémie COVID-19 odhalili citlivosť organizmu k tomuto infekčnému ochoreniu. Jedným z najdôležitejších faktorov zraniteľnosti ľudského organizmu je zníženie imunity v dôsledku deficitu mikroživín. V príspevku venujeme pozornosť dostatočnej koncentrácie vitamínu D v ľudskom organizme, nakoľko práve on aktivuje expresiu génov, ktoré sa podieľajú na ochrane pred koronavírusmi. Je rovnako dôležitý pre zmiernenie účinkov „cytokínovej búrky“, ako aj liečbe komorbidít. Včasná prevencia prispieva k významnému zníženiu počtu pacientov s ťažkým priebehom ochorenia COVID-19, úmrtnosti, a tým k zníženiu nákladov na zdravotnú starostlivosť. Preto sú potrebné okrem karanténnych aj preventívne opatrenia, ktoré zabránia prepuknutiu infekcie. V tomto smere je veľmi dôležitou súčasťou zachovanie a podpora antivírusovej imunity, zníženie rizika vzniku „cytokínovej búrky“ a liečba sprievodných patológií, ktoré zhoršujú priebeh koronavírusovej infekcie. Pre dosiahnutie týchto cieľov je rozhodujúcim krokom odstránenie deficitu mikroživín.
In addition to the COVID-19 pandemic, we are currently struggling with the micronutrient deficiency pandemic, especially vitamin D deficiency. At present, vitamin D deficiency occurs in almost 80% of the population, especially in marginalized groups. Previous findings from the COVID-19 pandemic revealed the body's susceptibility to this infectious disease. One of the most important factors in the vulnerability of the human body is the reduction of immunity due to micronutrient deficiency. In this paper, we pay attention to the sufficient concentration of vitamin D in the human body, as it activates the expression of genes that are involved in protection against coronaviruses. It is just as important in mitigating the effects of a "cytokine storm" as it is in treating comorbidities. Early prevention contributes to a significant reduction in the number of patients with severe COVID-19 disease, mortality, and thus to a reduction in health care costs. Therefore, in addition to quarantine, preventive measures are needed to prevent the outbreak of infection. In this regard, maintaining and promoting antiviral immunity, reducing the risk of a "cytokine storm" and treating concomitant pathologies that exacerbate the course of coronavirus infection are very important components. The achievement of micronutrient deficiencies is a crucial step in achieving these goals.
Kašel je jedním z charakteristických symptomů onemocnění horních cest dýchacích. Terapie kašle je velmi rozsáhle popsaná, ale pro správnou volbu léčby je nezbytná znalost fyziologických a patofyziologických procesů, které kašel způsobují. Pro úspěšnou léčbu se poté kromě expektorancií a antitusik v praxi dají použít i další skupiny chemických léčiv, rostlinná léčiva, ale i jiné látky, jako je například med nebo mentol.
Cough is among the characteristic symptoms of upper respiratory tract disease. The treatment of cough has been described extensively, but choosing the proper treatment requires the knowledge of physiological and pathophysiological processes that underlie cough. In addition to expectorants and antitussive drugs, other groups of chemical medicines, herbal remedies as well as other substances, such as honey or menthol, can be used for successful treatment of cough in the practice.
Imunitní systém je významnou složkou obranného zánětu, jehož úkolem je eliminace infekcí patogenními mikroorganismy a eliminace poškození vlastních struktur. Potenciál zapojit se do obranné reakce mají všechny buněčné struktury našeho těla. Obranná strategie je víceúrovňová. První obrannou linii představuje přirozená mikrobiota, která osídluje epitelové struktury a kůži. Druhou obrannou linií jsou epitely, které interagují s přirozenou mikrobiotou a se složkami imunity. Třetí obrannou linii tvoří vrozená imunita zahrnující její buněčný substrát, především dendritické buňky, makrofágy, granulocyty a NK buňky. Čtvrtá obranná linie je představována složkami specifické imunity T lymfocyty odpovědnými za buňkami zprostředkovanou imunitu a B lymfocyty, které představují buněčný substrát tvořící protilátky. Účinná obranná reakce vyžaduje přítomnost vitaminu D, C a také zinku, které pozitivně modulují potenciál všech čtyř obranných úrovní imunity. S ohledem na obecně nedostatečný příjem zmiňovaných látek ve stravě lze doporučit suplementaci v podobě potravních doplňků. Ta má být realizována preventivně s cílem snížit frekvenci a závažnost především virových infekcí.
The immune system is an integral part of protective inflammatory response with aims to eliminate invasion of pathogenic microorganisms and to eliminate self tissue damage. The potential to participate in protective immune reaction is given to all body cells. The protective strategy is multilevels. The first line is physiological microbiota which is inhabiting all epithelial structures of our body and skin. The second line is formed by epithelial linings which are interacting with both physiological microbiota and components of immunity. The third line of defence is innate immunity including its cellular substrate, namely dendritic cells, macrophages, granulocytes and NK cells. The forth defence line is adaptive specific immunity displayed by T and B lymphocytes. Efficient protection deserves the presence of vitamins D, C and elementary zinc which are able to positively modulate the protective potential of all lines of defence. It is evidenced that the intake of vitamin D, C and zinc by food is in majority of people insuficient to cope the requirements of these nutrients for optimal immune response. Therefore, supplementation is highly recommended to prevent especially viral infections.
- MeSH
- imunita imunologie účinky léků MeSH
- imunitní systém imunologie účinky léků MeSH
- imunologické faktory MeSH
- imunomodulace MeSH
- kyselina askorbová imunologie MeSH
- lidé MeSH
- potravní doplňky MeSH
- virové nemoci prevence a kontrola MeSH
- vitamin D imunologie MeSH
- zinek imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Vaccinia virus (VACV) is an enveloped DNA virus from the Orthopoxvirus family, various strains of which were used in the successful eradication campaign against smallpox. Both original and newer VACV-based replicating vaccines reveal a risk of serious complications in atopic individuals. VACV encodes various factors interfering with host immune responses at multiple levels. In atopic skin, the production of type I interferon is compromised, while VACV specifically inhibits the phosphorylation of the Interferon Regulatory Factor 3 (IRF-3) and expression of interferons. To overcome this block, we generated a recombinant VACV-expressing murine IRF-3 (WR-IRF3) and characterized its effects on virus growth, cytokine expression and apoptosis in tissue cultures and in spontaneously atopic Nc/Nga and control Balb/c mice. Further, we explored the induction of protective immune responses against a lethal dose of wild-type WR, the surrogate of smallpox. We demonstrate that the overexpression of IRF-3 by WR-IRF3 increases the expression of type I interferon, modulates the expression of several cytokines and induces superior protective immune responses against a lethal poxvirus challenge in both Nc/Nga and Balb/c mice. Additionally, the results may be informative for design of other virus-based vaccines or for therapy of different viral infections.
- MeSH
- exprese genu genetika MeSH
- imunita imunologie MeSH
- infekce vyvolané poxviry imunologie prevence a kontrola MeSH
- interferon typ I metabolismus MeSH
- interferonový regulační faktor 3 genetika imunologie MeSH
- interleukin-1beta imunologie MeSH
- kůže imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- Poxviridae patogenita MeSH
- regulace exprese virových genů genetika MeSH
- replikace viru imunologie MeSH
- vakcínie virologie MeSH
- virové vakcíny imunologie MeSH
- virus vakcinie genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
O-methylation is an unusual sugar modification with a function that is not fully understood. Given its occurrence and recognition by lectins involved in the immune response, methylated sugars were proposed to represent a conserved pathogen-associated molecular pattern. We describe the interaction of O-methylated saccharides with two β-propeller lectins, the newly described PLL2 from the entomopathogenic bacterium Photorhabdus laumondii, and its homologue PHL from the related human pathogen Photorhabdus asymbiotica. The crystal structures of PLL2 and PHL revealed up to 10 out of 14 potential binding sites per protein subunit to be occupied with O-methylated structures. The avidity effect strengthens the interaction by 4 orders of magnitude. PLL2 and PHL also interfere with the early immune response by modulating the production of reactive oxygen species and phenoloxidase activity. Since bacteria from Photorhabdus spp. have a complex life cycle involving pathogenicity towards different hosts, the involvement of PLL2 and PHL might contribute to the pathogen overcoming insect and human immune system defences in the early stages of infection. DATABASES: Structural data are available in PDB database under the accession numbers 6RG2, 6RGG, 6RFZ, 6RG1, 6RGU, 6RGW, 6RGJ, and 6RGR.
- MeSH
- bakteriální proteiny chemie metabolismus MeSH
- cukry metabolismus MeSH
- gramnegativní bakteriální infekce imunologie metabolismus mikrobiologie MeSH
- hemocyty imunologie metabolismus MeSH
- hemolymfa imunologie metabolismus MeSH
- imunita imunologie MeSH
- imunitní systém imunologie metabolismus MeSH
- interakce hostitele a patogenu imunologie MeSH
- lektiny chemie metabolismus MeSH
- lidé MeSH
- metylace MeSH
- můry MeSH
- Photorhabdus imunologie metabolismus fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The 2014-2016 Ebola outbreak in West Africa has triggered accelerated development of several preventive vaccines against Ebola virus. Under the EBOVAC1 consortium, three phase I studies were carried out to assess safety and immunogenicity of a two-dose heterologous vaccination regimen developed by Janssen Vaccines and Prevention in collaboration with Bavarian Nordic. To describe the immune response induced by the two-dose heterologous vaccine regimen, we propose a mechanistic ODE based model, which takes into account the role of immunological memory. We perform identifiability and sensitivity analysis of the proposed model to establish which kind of biological data are ideally needed in order to accurately estimate parameters, and additionally, which of those are non-identifiable based on the available data. Antibody concentrations data from phase I studies have been used to calibrate the model and show its ability in reproducing the observed antibody dynamics. Together with other factors, the establishment of an effective and reactive immunological memory is of pivotal importance for several prophylactic vaccines. We show that introducing a memory compartment in our calibrated model allows to evaluate the magnitude of the immune response induced by a booster dose and its long-term persistence afterwards.
- MeSH
- biologické modely * MeSH
- hemoragická horečka Ebola imunologie prevence a kontrola MeSH
- imunita * imunologie MeSH
- lidé MeSH
- vakcinace MeSH
- vakcíny proti ebole * imunologie MeSH
- virus Ebola * imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- západní Afrika MeSH
Autor se zamýšlí nad nemocemi z nachlazení v souvislosti se zráním imunitního systému v různých údobích dětského života. Popisuje specifika kojeneckého, batolecího, předškolního a školního věku dětí a možnosti zvládání těchto onemocnění praktickými lékaři pro děti a dorost či specialisty v oboru alergologie a klinické imunologie. V závěru zdůrazňuje význam rodiny a školy při zvyšování odolnosti dětí proti nemocem z prochlazení.
The author thinks about colds related to immune system maturation in various childhood stages. It describes the specifics of babies, toddlers, pre-school and school age children and the possibilities of coping with these diseases by GPs for children and adolescents or specialists in the field of allergology and clinical immunology. In conclusion it emphasizes the importance of the family and school in increasing the resistance of children against the diseases of exacerbation.
- MeSH
- dítě MeSH
- imunita * fyziologie genetika imunologie MeSH
- kašel prevence a kontrola MeSH
- kolektivní imunita genetika imunologie MeSH
- laryngitida prevence a kontrola MeSH
- lidé MeSH
- nachlazení imunologie klasifikace prevence a kontrola MeSH
- odolnost vůči nemocem genetika imunologie MeSH
- otitis media prevence a kontrola MeSH
- přirozená imunita fyziologie genetika imunologie MeSH
- rinitida prevence a kontrola MeSH
- tělesná výkonnost MeSH
- vakcinace * metody trendy zákonodárství a právo MeSH
- zdravá strava metody trendy MeSH
- zdravý životní styl * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
Background MDA5 and RIG-1 are the important intracellular receptors which detect microbial associated molecular patterns. Septicemia is a condition in which infection enters the bloodstream of the patients. The main intracellular mechanisms against septicemia are yet to be clarified. Therefore, this research study was aimed to evaluate expression of MDA5 and RIG-1 in the patients suffering from septicemia in comparison to healthy controls. Methods MDA5 and RIG-1 expression levels in 40 patients suffering from septicemia and 40 healthy controls were evaluated using Real-Time PCR technique. The sources of bacteria in the bloodstream of the patients suffering from septicemia were determined using microbial cultures. Results The results showed that mRNA levels of MDA5 and RIG-1 were significantly increased in the patients when compared to healthy controls. The results also revealed that the patients were infected with four bacteria including Escherichia coli, Staphylococcus aureus, Acinetobacter baumannii and Pseudomonas aeruginosa. mRNA levels of MDA5 and RIG-1 did not differ among patients with various bacterial infections. Conclusion Based on the results it seems that MDA5 and RIG-1 are the main intracellular immunity against the bacteria during septicemia and could be considered for their roles in induction of immunity.
- MeSH
- biologické markery MeSH
- imunita genetika imunologie MeSH
- krev imunologie mikrobiologie MeSH
- lidé MeSH
- melatoninové receptory genetika imunologie krev MeSH
- receptory kyseliny retinové genetika imunologie krev MeSH
- sepse * genetika imunologie mikrobiologie MeSH
- transkripční faktory MeSH
- Check Tag
- lidé MeSH
Immunity plays an important role in the reactivity of the organism and, in this context, is an essential factor in the pathogenesis of many diseases. Basically, there is no system or organ in the body, whose dysfunction is not related to immunity consequences. In addition, there are also multisystem diseases simultaneously involving multiple body systems. They are not always caused by weak immunity, but also often by modified immune reactions known as overshooting. The essence of all these diseases is a change in the reactivity of the organism where immunity plays an important role. The immunity as such is then part of the systems of neuroendocrine-immune regulation, which have common mediators and receptors. The establishment of psychoneuroimmunology, a relatively new discipline in neuroscience, contributed to a detailed understanding of these mechanisms between central and peripheral nervous system, the endocrine system and the immune system. This research enabled the uncovering of the nature of stress-diseases and impact of other regulatory disturbances on the function of various body organs and systems of the organism as a whole. The aim of this short review is to show complex interconnections of these relationships to better understand the human health and disease.
- MeSH
- imunita imunologie fyziologie MeSH
- imunologické faktory MeSH
- lidé MeSH
- neurosekreční systémy imunologie fyziologie MeSH
- psychický stres imunologie MeSH
- psychoneuroimunologie * MeSH
- regulace genové exprese genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
