Trained immunity
Dotaz
Zobrazit nápovědu
The concept of trained immunity has become one of the most interesting and potentially commercially and clinically relevant ideas of current immunology. Trained immunity is realized by the epigenetic reprogramming of non-immunocompetent cells, primarily monocytes/macrophages and natural killer (NK) cells, and is less specific than adaptive immunity; therefore, it may cross-protect against other infectious agents. It remains possible, however, that some of the observed changes are simply caused by increased levels of immune reactions resulting from supplementation with immunomodulators, such as glucan. In addition, the question of whether we can talk about trained immunity in cells with a life span of only few days is still unresolved.
- MeSH
- adaptivní imunita * MeSH
- beta-glukany metabolismus MeSH
- buněčná imunita MeSH
- buňky NK imunologie metabolismus MeSH
- homeostáza imunologie MeSH
- leukocyty imunologie metabolismus MeSH
- lidé MeSH
- lymfocyty imunologie metabolismus MeSH
- makrofágy imunologie metabolismus MeSH
- monocyty imunologie metabolismus MeSH
- náchylnost k nemoci MeSH
- přirozená imunita * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Recent evidence shows that innate immune cells, in addition to B and T cells, can retain immunological memory of their encounters and afford long-term resistance against infections in a process known as 'trained immunity'. However, the duration of the unspecific protection observed in vivo is poorly compatible with the average lifespan of innate immune cells, suggesting the involvement of long-lived cells. Accordingly, recent studies demonstrate that hematopoietic stem and progenitor cells (HSPCs) lay at the foundation of trained immunity, retaining immunological memory of infections and giving rise to a "trained" myeloid progeny for a long time. In this review, we discuss the research demonstrating the involvement of HSPCs in the onset of long-lasting trained immunity. We highlight the roles of specific cytokines and Toll-like receptor ligands in influencing HSPC memory phenotypes and the molecular mechanisms underlying trained immunity HSPCs. Finally, we discuss the potential benefits and drawbacks of the long-lasting trained immune responses, and describe the challenges that the field is facing.
- MeSH
- cytokiny imunologie MeSH
- hematopoetické kmenové buňky imunologie MeSH
- imunologická paměť imunologie MeSH
- lidé MeSH
- ligandy MeSH
- přirozená imunita imunologie MeSH
- toll-like receptory imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Pozdní následky infekčních onemocnění, označované jako pozdní infekční syndrom, představují déletrvající a také výraznější zdravotní problémy, které se mohou vyskytnout po akutní virové, bakteriální nebo parazitární infekci. Jako jeden z klíčových konceptů pro pochopení těchto dlouhodobých efektů se jeví trénovaná imunita, spojená s funkčním přeprogramováním vrozených imunitních buněk prostřednictvím epigenetického a metabolického přepojení. Trvání trénovaných imunitních reakcí se liší v závislosti na povaze podnětu a intenzitě vyvolané imunitní odpovědi. Její nadměrná aktivace zvyšuje riziko autoinflamatorních a autoimunitních poruch, neurodegenerativních syndromů, aterosklerózy a kardiovaskulárních onemocnění, naproti tomu potlačení efektorových funkcí imunitních buněk vede k postinfekční imunitní paralýze.
The late consequences of infectious diseases, referred to as post-acute infection, represent longer-lasting and more pronounced health problems that can occur after an acute viral, bacterial or parasitic infection. A key concept for understanding these long-term effects appears to be trained immunity, associated with functional reprogramming of innate immune cells through epigenetic and metabolic rewiring. The duration of trained immune responses varies depending on the nature of the stimulus and the intensity of the immune response elicited. Its excessive activation increases the risk of autoinflammatory and autoimmune disorders, neurodegenerative syndromes, atherosclerosis and cardiovascular diseases, while suppression of the effector functions of immune cells leads to post-infectious immune paralysis.
The innate immunity is frequently accepted as a first line of relatively primitive defense interfering with the pathogen invasion until the mechanisms of 'privileged' adaptive immunity with the production of antibodies and activation of cytotoxic lymphocytes 'steal the show'. Recent advancements on the molecular and cellular levels have shaken the traditional view of adaptive and innate immunity. The innate immune memory or 'trained immunity' based on metabolic changes and epigenetic reprogramming is a complementary process insuring adaptation of host defense to previous infections.Innate immune cells are able to recognize large number of pathogen- or danger- associated molecular patterns (PAMPs and DAMPs) to behave in a highly specific manner and regulate adaptive immune responses. Innate lymphoid cells (ILC1, ILC2, ILC3) and NK cells express transcription factors and cytokines related to subsets of T helper cells (Th1, Th2, Th17). On the other hand, T and B lymphocytes exhibit functional properties traditionally attributed to innate immunity such as phagocytosis or production of tissue remodeling growth factors. They are also able to benefit from the information provided by pattern recognition receptors (PRRs), e.g. γδT lymphocytes use T-cell receptor (TCR) in a manner close to PRR recognition. Innate B cells represent another example of limited combinational diversity usage participating in various innate responses. In the view of current knowledge, the traditional black and white classification of immune mechanisms as either innate or an adaptive needs to be adjusted and many shades of gray need to be included.
- MeSH
- adaptivní imunita * MeSH
- B-lymfocyty imunologie MeSH
- buňky NK imunologie MeSH
- cytokiny genetika imunologie MeSH
- lidé MeSH
- přirozená imunita * MeSH
- T-lymfocyty imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Článek shrnuje historii poznávání vztahu výživy a imunity. Myšlenka podpory zdraví vhodnou stravou byla známa již starověkým lékařům, což dokumentuje Hippokratův (460–337 př. n. l.) citát „Když nevíš nic o stravě člověka, jak můžeš porozumět jeho nemoci.“ Často se ale na tuto mnohokrát ověřenou zkušenost na dlouhá desetiletí pozapomnělo, jak to už v dějinách lidského poznávání bývá, a zvláště pak v historii medicíny. Strava nemá jen význam výživový, ale má také přímý vliv na imunitu. V této souvislosti je si třeba uvědomit, že každá strava obsahuje antigeny, které přímo indukují imunologickou reakci v našem největším imunitním orgánu, lymfoidní tkání těsně nasedající na střevo (GALT). Každá imunitní reakce je vždy provázena vznikem imunologické paměti, a to jak imunity specifické (adaptivní), tak také, jak bylo nedávno prokázáno, i imunity nespecifické (přirozené), která je označována jako „vyškolená imunita.“ Přijímání potravy ve své podstatě znamená tedy neustále probíhající vakcinaci, stále se opakující indukci imunologických pamětí obou typů imunity, tzn. jak specifické (adaptivní), tak nespecifické (vyškolené).
The article summarizes the history of discovery of the relationship between nutrition and immunity. The idea of promoting good health through a right diet was already known to ancient physicians, as evidenced by Hippocrates' (460–337 BC) quote, "If you know nothing about a person's diet, how can you understand his illnesses." Diet not only has a nutritional meaning, but also has a direct effect on immunity. In this context, it is important to realize that every diet contains antigens that directly induce an immune response in our largest immune organ, the intestinal lymphoid tissue (GALT), which is always accompanied by the development of immunological memory, both immune specific (adaptive), as has recently been shown, non-specific immunity, which is referred to as "trained immunity". However, this time-tested experience has often been forgotten for many decades, as is the case in the history of human cognition, and especially in the history of medicine. Diet not only has a nutritional significance, but also it has a direct effect on immune status. In this context, it is important to realize that every diet contains antigens that directly induce an immune response in our largest immune organ, the intestinal lymphoid tissue (GALT), which is always accompanied by the development of immunological memory, both specific (adaptive) immunity, and as it has recently been shown, non-specific (natural) immunity, which is referred to as "trained immunity". In essence, food intake therefore means ongoing vaccination, a constantly recurring induction of immunological memories of both types, the specific (adaptive), and the non-specific (trained).
- MeSH
- fyziologie výživy * MeSH
- imunita * MeSH
- imunologická paměť MeSH
- lidé MeSH
- primární prevence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
COVID-19 is a severe health problem in many countries and has altered day-to-day life in the whole world. This infection is caused by the SARS-CoV-2 virus, and depending on age, sex and health status of the patient, it can present with variety of clinical symptoms such as mild infection, a very severe form or even asymptomatic course of the disease. Similarly to other viruses, innate immune response plays a vital role in protection against COVID-19. However, dysregulation of innate immunity could have a significant influence on the severity of the disease. Despite various efforts, there is no effective vaccine against the disease so far. Recent data have demonstrated that the Bacillus Calmette-Guérin (BCG) vaccine could reduce disease severity and the burden of several infectious diseases in addition to targeting its primary focus tuberculosis. There is growing evidence for the concept of beneficial non-specific boosting of immune responses by BCG or other microbial compounds termed trained immunity, which may protect against COVID-19. In this manuscript, we review data on how the development of innate immune memory due to microbial compounds specifically BCG can result in protection against SARS-CoV-2 infection. We also discuss possible mechanisms, challenges and perspectives of using innate immunity as an approach to reduce COVID-19 severity.
- Publikační typ
- časopisecké články MeSH
- přehledy 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
Mikroorganismy si během evoluce vyvinuly širokou škálu strategií, jak uniknout vrozenému i adaptivnímu imunitnímu systému, a některým těmto strategiím se věnujeme v našem přehledu. Mikroorganismy mohou využívat podobnost svých proteinů s proteiny hostitele, produkovat protizánětlivé faktory, narušovat komplementový systém, ovlivňovat funkci a blokovat syntézu cytokinů, inhibovat rozpoznávání imunoglobulinů, snižovat expresi a modifikovat antigeny na svém povrchu, narušovat zpracování a prezentaci antigenu imunitními buňkami, vstupovat do imunitních buněk, ovlivňovat apoptózu buněk, modulovat funkce imunitních buněk nebo ovlivňovat produkci hormonů. S těmito únikovými strategiemi je nutné počítat při léčbě infekčních onemocnění.
Microorganisms have evolved a wide variety of strategies to evade both the innate and adaptive immune systems during evolution, and some of these strategies are addressed in our review. Microorganisms can use the similarity of their proteins to host proteins, produce anti-inflammatory factors, disrupt the complement system, affect the function and block the synthesis of cytokines, inhibit the recognition of immunoglobulins, reduce the expression and modify antigens on their surface, disrupt the processing and presentation of antigen by immune cells, enter immune cells , influence cell apoptosis, modulate immune cell functions or influence hormone production. These escape strategies must be taken into account when treating infectious diseases.
- Klíčová slova
- únikové strategie mikroorganismů,
- MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- mikrobiologické jevy * MeSH
- přirozená imunita * MeSH
- trénovaná imunita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Hypoxia training can improve endurance performance. However, the specific benefits mechanism of hypoxia training is controversial, and there are just a few studies on the peripheral adaptation to hypoxia training. The main objective of this study was to observe the effects of hypoxia training on cutaneous blood flow (CBF), hypoxia-inducible factor (HIF), nitric oxide (NO), and vascular endothelial growth factor (VEGF). Twenty rowers were divided into two groups for four weeks of training, either hypoxia training (Living High, Exercise High and Training Low, HHL) or normoxia training (NOM). We tested cutaneous microcirculation by laser Doppler flowmeter and blood serum parameters by ELISA. HHL group improved the VO(2peak) and power at blood lactic acid of 4 mmol/l (P(4)) significantly. The CBF and the concentration of moving blood cells (CMBC) in the forearm of individuals in the HHL group increased significantly at the first week. The HIF level of the individuals in the HHL group increased at the fourth week. The NO of HHL group increased significantly at the fourth week. In collusion, four weeks of HHL training resulted in increased forearm cutaneous blood flow and transcutaneous oxygen pressure. HHL increases rowers' NO and VEGF, which may be the mechanism of increased blood flow. The increased of CBF seems to be related with improving performance.
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- faktor 1 indukovatelný hypoxií krev MeSH
- fyzická vytrvalost * MeSH
- fyziologická neovaskularizace MeSH
- hypoxie patofyziologie MeSH
- kondiční příprava metody MeSH
- kůže krevní zásobení MeSH
- lidé MeSH
- mikrocirkulace * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- oxid dusnatý krev MeSH
- regionální krevní průtok MeSH
- rychlost toku krve MeSH
- spotřeba kyslíku MeSH
- svalová síla MeSH
- vaskulární endoteliální růstové faktory krev MeSH
- vazodilatace MeSH
- vodní sporty * MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH