Adaptive immunity
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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
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
The adaptive immune system is responsible for generating immunological response and immunological memory. Regulation of adaptive immunity including B cell and T cell biology was mainly understood from the protein and microRNA perspective. However, long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNAs (ncRNAs) that influence key factors in lymphocyte biology such as NOTCH, PAX5, MYC and EZH2. LncRNAs were described to modulate lymphocyte activation by regulating pathways such as NFAT, NFκB, MYC, interferon and TCR/BCR signalling (NRON, NKILA, BCALM, GAS5, PVT1), and cell effector functions (IFNG-AS1, TH2-LCR). Here we review lncRNA involvement in adaptive immunity and the implications for autoimmune diseases (multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis) and T/B cell leukaemias and lymphomas (CLL, MCL, DLBCL, T-ALL). It is becoming clear that lncRNAs are important in adaptive immune response and provide new insights into its orchestration.
- MeSH
- adaptivní imunita genetika MeSH
- aktivace lymfocytů genetika MeSH
- lidé MeSH
- nemoc genetika MeSH
- RNA dlouhá nekódující genetika fyziologie MeSH
- signální transdukce genetika imunologie MeSH
- T-lymfocyty fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Aging is generally regarded as an irreversible process, and its intricate relationship with the immune system has garnered significant attention due to its profound implications for the health and well-being of the aging population. As people age, a multitude of alterations occur within the immune system, affecting both innate and adaptive immunity. In the realm of innate immunity, aging brings about changes in the number and function of various immune cells, including neutrophils, monocytes, and macrophages. Additionally, certain immune pathways, like the cGAS-STING, become activated. These alterations can potentially result in telomere damage, the disruption of cytokine signaling, and impaired recognition of pathogens. The adaptive immune system, too, undergoes a myriad of changes as age advances. These include shifts in the number, frequency, subtype, and function of T cells and B cells. Furthermore, the human gut microbiota undergoes dynamic changes as a part of the aging process. Notably, the interplay between immune changes and gut microbiota highlights the gut's role in modulating immune responses and maintaining immune homeostasis. The gut microbiota of centenarians exhibits characteristics akin to those found in young individuals, setting it apart from the microbiota observed in typical elderly individuals. This review delves into the current understanding of how aging impacts the immune system and suggests potential strategies for reversing aging through interventions in immune factors.
- MeSH
- adaptivní imunita * MeSH
- lidé MeSH
- přirozená imunita * MeSH
- stárnutí * imunologie MeSH
- střevní mikroflóra * imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Chronická lymfocytární leukemie, nejčastější leukemie dospělých v západním světě, je spojena s významným kombinovaným imunodeficitem. U neléčených nemocných je již v časných fázích onemocnění přítomen deficit imunoglobulinů. Nepříznivý prognostický význam byl prokázán u hypogamaglobulinémie ve třídě IgA. Důsledkem je vyšší frekvence zejména bakteriálních infekcí. Dále dochází ke změnám počtu i imunofenotypu T-lymfocytů s inverzí poměru CD4+ a CD8+ buněk a zvýšením počtu regulačních T-lymfocytů. Funkční změny T-lymfocytů jsou popisovány jako stav pseudovyčerpání, charakteristický poruchou tvorby imunologických synapsí. Produkce cytokinů a diferenciace buněk imunitního systému je posunuta ve směru Th2 imunitní odpovědi. Důsledkem těchto změn je větší náchylnost pacientů k infekcím oportunními patogeny a viry. Další změny postihují i nespecifickou imunitu – NK buňky, neutrofily, monocyty/ makrofágy a komplement. V tomto článku jsou přehledně shrnuty hlavní změny specifické imunity u neléčených nemocných s chronickou lymfocytární leukemií.
Chronic lymphocytic leukaemia, the most common leukaemia of adults in the western world, is associated with significant combined immunodeficiency. Even treatment-naive patients with early stages of the disease can have immunoglobulin deficiency. IgA hypogammaglobulinemia was shown to be a negative prognostic factor, leading to a higher frequency of bacterial infections. There are changes in both the number and immunophenotype of T-cells with inversion of the CD4+/CD8+ ratio and an increase in regulatory T-cells. Changes in T-cell function are described as pseudo-exhaustion, characterised by the inability to form immunological synapses. Furthermore, the cytokine spectrum and immune cell differentiation indicate a shift towards Th2 immune response. These changes lead to increased susceptibility to opportunistic and viral infections. There are changes of innate immunity as well NK cells, neutrophils, monocytes/macrophages and the complement system are all affected. In this article, major adaptive immunity changes in treatment-naive patients are summarized.
- MeSH
- agamaglobulinemie etiologie MeSH
- B-lymfocyty MeSH
- buněčná imunita MeSH
- chronická lymfatická leukemie * imunologie komplikace MeSH
- humorální imunita MeSH
- infekce etiologie MeSH
- lidé MeSH
- syndromy imunologické nedostatečnosti * etiologie MeSH
- T-lymfocyty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
There is no doubt that immunotherapy lies in the spotlight of current cancer research and clinical trials. However, there are still limitations in the treatment response in certain types of tumors largely due to the presence of the complex network of immunomodulatory and immunosuppressive pathways. These limitations are not likely to be overcome by current immunotherapeutic options, which often target isolated steps in immune pathways preferentially involved in adaptive immunity. Recently, we have developed an innovative anti-cancer immunotherapeutic strategy that initially elicits a strong innate immune response with subsequent activation of adaptive immunity in mouse models. Robust primary innate immune response against tumor cells is induced by toll-like receptor ligands and anti-CD40 agonistic antibodies combined with the phagocytosis-stimulating ligand mannan, anchored to a tumor cell membrane by biocompatible anchor for membrane. This immunotherapeutic approach results in a dramatic therapeutic response in large established murine subcutaneous tumors including melanoma, sarcoma, pancreatic adenocarcinoma, and pheochromocytoma. Additionally, eradication of metastases and/or long-lasting resistance to subsequent re-challenge with tumor cells was also accomplished. Current and future advantages of this immunotherapeutic approach and its possible combinations with other available therapies are discussed in this review.
- MeSH
- adaptivní imunita MeSH
- fagocytóza účinky léků imunologie MeSH
- imunitní systém imunologie metabolismus MeSH
- imunomodulace MeSH
- imunoterapie * metody MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- ligandy MeSH
- nádorové mikroprostředí účinky léků genetika imunologie MeSH
- nádory etiologie metabolismus patologie terapie MeSH
- přirozená imunita MeSH
- protinádorové látky imunologicky aktivní farmakologie terapeutické užití MeSH
- toll-like receptory metabolismus MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Research Support, N.I.H., Intramural MeSH
- Klíčová slova
- vycvičená imunita,
- MeSH
- adaptivní imunita MeSH
- bezobratlí imunologie MeSH
- imunita rostlin MeSH
- imunitní systém - jevy * MeSH
- imunologická paměť * MeSH
- obratlovci imunologie MeSH
- PAMP struktury MeSH
- přirozená imunita MeSH
- rostliny MeSH
- Publikační typ
- přehledy MeSH
Aktivní vitamin D3 je klíčovým hráčem v řadě patologických stavů. V přehledu se zabývám jeho vlivem na imunitní systém, a to jak na oblast přirozené, tak adaptivní imunity. D3 má též význam při obraně proti infekcím a rozvoji imunopatologických reakcí, především v autoimunitě.
Active vitamin D3 is a key factor in many pathological states. In this review its influence on the immune system will be discussed, especially in the scope of innate and adaptive immunity. D3 has a crucial importance in defense against infections and in development of immunopathological reactions, especially in autoimmunity.
- MeSH
- adaptivní imunita MeSH
- autoimunita imunologie MeSH
- buněčná imunita imunologie MeSH
- cholekalciferol imunologie MeSH
- financování organizované MeSH
- infekce MeSH
- lidé MeSH
- přirozená imunita imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
IL-2 was initially characterized as a T cell growth factor in the 1970s, and has been studied intensively ever since. Decades of research have revealed multiple and diverse roles for this potent cytokine, indicating a unique linking role between adaptive and innate arms of the immune system. Here, we review the literature showing that IL-2 is expressed in a plethora of cell types across the immune system, where it has indispensable functions in orchestrating cellular interactions and shaping the nature and magnitude of immune responses. Emerging from the basic research that has revealed the molecular mechanisms and the complexity of the biologic actions of IL-2, several immunotherapeutic approaches have now focused on manipulating the levels of this cytokine in patients. These strategies range from inhibition of IL-2 to achieve immunosuppression, to the application of IL-2 as a vaccine adjuvant and in cancer therapies. This review will systematically summarize the major findings in the field and identify key areas requiring further research in order to realize the potential of IL-2 in the treatment of human diseases.
Role vitaminu D je klasicky spojována především s kalcium-fosfátovým metabolismem. V posledních letech však máme stále více informací o jeho významném imunoregulačním vlivu, a to jak na vrozenou, tak adaptivní imunitu. Vitamin D má svůj význam při ochraně před patogenními mikroorganismy i v udržení imunotolerance a jeho nedostatek bývá spojován s infekcemi, autoimunitními či nádorovými chorobami.
Vitamin D is associated primarily with calcium-phosphate metabolism. However, in recent years we have many studies demontrating its significant immunoregulatory effect, both on innate and adaptive immunity. Vitamin D is important in protection against pathogenic microorganisms and in maintaining immunotolerance, and its deficiency is assumed to be associated with infections, autoimmune or cancer diseases.
- MeSH
- adaptivní imunita fyziologie MeSH
- imunomodulace * fyziologie MeSH
- kalcitriol analýza fyziologie imunologie MeSH
- lidé MeSH
- lymfocyty fyziologie imunologie MeSH
- nedostatek vitaminu D imunologie MeSH
- přirozená imunita fyziologie MeSH
- vitamin D * analýza fyziologie imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH