adaptive responses
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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.
- Klíčová slova
- adaptive immunity, immunological memmory, innate immunity, innate recognition, trained immunity,
- 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
- Názvy látek
- cytokiny MeSH
In order to understand how olfactory stimuli are encoded and processed in the brain, it is important to build a computational model for olfactory receptor neurons (ORNs). Here, we present a simple and reliable mathematical model of a moth ORN generating spikes. The model incorporates a simplified description of the chemical kinetics leading to olfactory receptor activation and action potential generation. We show that an adaptive spike threshold regulated by prior spike history is an effective mechanism for reproducing the typical phasic-tonic time course of ORN responses. Our model reproduces the response dynamics of individual neurons to a fluctuating stimulus that approximates odorant fluctuations in nature. The parameters of the spike threshold are essential for reproducing the response heterogeneity in ORNs. The model provides a valuable tool for efficient simulations of olfactory circuits.
- Klíčová slova
- adaptive threshold, integrate-and-fire model, olfactory receptor neuron,
- MeSH
- akční potenciály fyziologie MeSH
- biologické modely MeSH
- čichové buňky účinky léků fyziologie MeSH
- elektrofyziologické jevy MeSH
- fyziologická adaptace * MeSH
- můry fyziologie MeSH
- sexuální lákadla farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- sexuální lákadla MeSH
The exposure of living organisms to environmental stress triggers defensive responses resulting in the activation of protective processes. Whenever the exposure occurs at low doses, defensive effects overwhelm the adverse effects of the exposure; this adaptive situation is referred to as "hormesis". Environmental, physical, and nutritional hormetins lead to the stimulation and strengthening of the maintenance and repair systems in cells and tissues. Exercise, heat, and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair-, and anti-oxidative-stress responses. The health promoting effect of many bio-actives in fruits and vegetables can be seen as the effect of mildly toxic compounds triggering this adaptive stimulus. Numerous studies indicate that living organisms possess the ability to adapt to adverse environmental conditions, as exemplified by the fact that DNA damage and gene expression profiling in populations living in the environment with high levels of air pollution do not correspond to the concentrations of pollutants. The molecular mechanisms of the hormetic response include modulation of (a) transcription factor Nrf2 activating the synthesis of glutathione and the subsequent protection of the cell; (b) DNA methylation; and (c) microRNA. These findings provide evidence that hormesis is a toxicological event, occurring at low exposure doses to environmental stressors, having the benefit for the maintenance of a healthy status.
- Klíčová slova
- adaptive response, microRNA machinery, preventive medicine,
- MeSH
- epigeneze genetická * MeSH
- fyziologická adaptace * MeSH
- fyziologický stres * MeSH
- hormeze * MeSH
- lidé MeSH
- oxidační stres MeSH
- poškození DNA MeSH
- regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Although physiological responses to chronic hypoxia, including pulmonary hypertension and right ventricular hypertrophy, have been well described, the molecular mechanisms involved in cardiopulmonary adaptations are still not fully understood. We hypothesize that adaptive responses to chronic hypoxia are the result of altered transcriptional regulations in the right and left ventricles. Here we report results from the gene expression profiling of adaptive responses in a chronically hypoxic heart. Of 11 analyzed candidate genes, the expression of seven and four genes, respectively, was significantly altered in the right ventricle of hypoxic male and female mice. In the transcriptional profile of the left ventricle, we identified a single expression change in hypoxic males (Vegfa gene). To directly test the role of HIF1, we analyzed the expression profile in Hif1a partially deficient mice exposed to moderate hypoxia. Our data showed that Hif1a partial deficiency significantly altered transcriptional profiles of analyzed genes in hypoxic hearts. The expression changes were only detected in two genes in the right ventricle of Hif1a(+/-) males and in one gene in the right ventricle of Hif1a(+/-) females. First, our results suggest that hypoxia mainly affects adaptive expression profiles in the right ventricle and that each ventricle can respond independently. Second, our findings indicate that HIF1a plays an important role in adaptive cardiopulmonary responses and the dysfunction of HIF1 pathways considerably affects transcriptional regulation in the heart. Third, our data reveal significant differences between males and females in cardiac adaptive responses to hypoxia and indicate the necessity of optimizing diagnostic and therapeutic procedures in clinical practice, with respect to sex.
- MeSH
- časové faktory MeSH
- chronická nemoc MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa nedostatek genetika metabolismus MeSH
- fyziologická adaptace MeSH
- genetická transkripce MeSH
- hematokrit MeSH
- hypoxie genetika metabolismus patofyziologie MeSH
- kardiomegalie genetika metabolismus patofyziologie MeSH
- krevní tlak MeSH
- messenger RNA metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- plicní hypertenze genetika metabolismus patofyziologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- regulace genové exprese MeSH
- sexuální faktory MeSH
- srdce - funkce komor genetika MeSH
- srdeční komory metabolismus patofyziologie MeSH
- stanovení celkové genové exprese * metody MeSH
- tělesná hmotnost MeSH
- vaskulární endoteliální růstový faktor A genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
- Hif1a protein, mouse MeSH Prohlížeč
- messenger RNA MeSH
- vascular endothelial growth factor A, mouse MeSH Prohlížeč
- vaskulární endoteliální růstový faktor A MeSH
Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
- MeSH
- aklimatizace fyziologie MeSH
- časové faktory MeSH
- fenotyp * MeSH
- klimatické změny * MeSH
- ptáci fyziologie MeSH
- selekce (genetika) fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- systematický přehled 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.
- Klíčová slova
- adaptive immunity, aging, cGAS-STING, gut microbiota, gut microbiota aging, innate immunity,
- 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
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.
- Klíčová slova
- Adaptive immunity, Autoimmune diseases, B cell, B/T cell activation, Leukaemia, LncRNAs, Lymphocyte development, Lymphoma, T cell, T cell polarization,
- 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
- Názvy látek
- RNA dlouhá nekódující MeSH
Mycobacterium tuberculosis (Mtb) remains a major threat worldwide, although only a fraction of infected individuals develops tuberculosis (TB). TB susceptibility is shaped by multiple genetic factors, and we performed comparative immunological analysis of two mouse strains to uncover relevant mechanisms underlying susceptibility and resistance. C57BL/6 mice are relatively TB-resistant, whereas I/St mice are prone to develop severe TB, partly due to the MHC-II allelic variant that shapes suboptimal CD4+ T cell receptor repertoire. We investigated the repertoires of lung-infiltrating helper T cells and B cells at the progressed stage in both strains. We found that lung CD4+ T cell repertoires of infected C57BL/6 but not I/St mice contained convergent TCR clusters with functionally confirmed Mtb specificity. Transcriptomic analysis revealed a more prominent Th1 signature in C57BL/6, and expression of pro-inflammatory IL-16 in I/St lung-infiltrating helper T cells. The two strains also showed distinct Th2 signatures. Furthermore, the humoral response of I/St mice was delayed, less focused, and dominated by IgG/IgM isotypes, whereas C57BL/6 mice generated more Mtb antigen-focused IgA response. We conclude that the inability of I/St mice to produce a timely and efficient anti-Mtb adaptive immune responses arises from a suboptimal helper T cell landscape that also impacts the humoral response, leading to diffuse inflammation and severe disease.
- Klíčová slova
- B cells, CD4 + T cells, TB-susceptible mouse strain, TCR repertoire, immunoglobulins, transcriptomic signatures, tuberculosis,
- MeSH
- adaptivní imunita * genetika MeSH
- B-lymfocyty imunologie MeSH
- genetická predispozice k nemoci * MeSH
- modely nemocí na zvířatech MeSH
- Mycobacterium tuberculosis * imunologie MeSH
- myši inbrední C57BL * MeSH
- myši MeSH
- plíce imunologie patologie MeSH
- receptory antigenů T-buněk genetika imunologie MeSH
- tuberkulóza * imunologie genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- receptory antigenů T-buněk MeSH
The miRNA-206 and miRNA-23a play an important role in muscle tissue hypertrophy, regeneration and atrophy. Both of these miRNAs have been highlighted as promising adaptation predictors; however, the available evidence on associations is inconclusive. Therefore, our aim was to assess the expression levels of these two miRNAs as predictors of change in muscle function during strength training and physical inactivity among dialysed patients. For this purpose, 46 haemodialysis patients were monitored for 12-weeks of either intradialytic strength training (EXG, n = 20) or physical inactivity during dialysis (CON, n = 26). In both groups of patients, we assessed the baseline expression levels of miRNA-23a and miRNA-206 and the isometric force generated during hip flexion (HF) contraction before and after the 12-week period. Among the EXG group, the expression of miRNA-206 predicted the change in HF (R2 = 0.63, p = 0.0005) much more strongly than the expression of miRNA-23a (R2 = 0.21, p = 0.027). Interestingly, baseline miRNA-23a (R2 = 0.30, p = 0.006) predicted the change in HF much more than miRNA-206 (p = ns) among the CON group. Our study indicates that the baseline expression of miRNA-206 could predict the response to strength training, while miRNA-23a could serve as a potential predictive marker of functional changes during physical inactivity in dialysis patients.
- MeSH
- biologické markery analýza MeSH
- dialýza ledvin metody MeSH
- fyziologická adaptace MeSH
- kondiční příprava zvířat * MeSH
- kosterní svaly metabolismus patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA analýza genetika MeSH
- odporový trénink * MeSH
- sedavý životní styl * MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- mikro RNA MeSH
This study revises our understanding of the effectiveness of cell-mediated adaptive immunity and treatment against microsporidia using molecular detection and quantification of microsporidia in immunocompetent C57Bl/6 and immunodeficient CD4-/- and CD8-/- mice for the first time. We demonstrate an intense dissemination of microsporidia into most organs within the first weeks post-infection in all strains of mice, followed by a chronic infection characterized by microsporidia persistence in CD4-/- and C57Bl/6 mice and a lethal outcome for CD8-/- mice. Albendazole application reduces microsporidia burden in C57Bl/6 and CD4-/- mice, whereas CD8-/- mice experience only a temporary effect of the treatment. Surprisingly, treated CD8-/- mice survived the entire experimental duration despite enormous microsporidia burden. On the basis of our results, we conclude that microsporidia survive despite the presence of immune mechanisms and treatments that are currently considered to be effective and therefore that CD8 T lymphocytes represent a major, but not sole effector mechanism controlling microsporidiosis. Furthermore, the survival of mice does not correspond to spore burden, which provides new insight into latent microsporidiosis from an epidemiological point of view.
- Klíčová slova
- CD4 T lymphocytes, Cell, CD8+ T lymphocytes, Cell, Encephalitozoon cuniculi, Parasite,
- MeSH
- adaptivní imunita imunologie MeSH
- albendazol terapeutické užití MeSH
- anthelmintika terapeutické užití MeSH
- buněčná imunita imunologie MeSH
- CD4-pozitivní T-lymfocyty imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- Encephalitozoon cuniculi růst a vývoj imunologie MeSH
- encephalitozoonóza imunologie mikrobiologie MeSH
- lymfopenie imunologie MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- albendazol MeSH
- anthelmintika MeSH