Cell Recognition
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Primary interaction of an intracellular bacterium with its host cell is initiated by activation of multiple signaling pathways in response to bacterium recognition itself or as cellular responses to stress induced by the bacterium. The leading molecules in these processes are cell surface membrane receptors as well as cytosolic pattern recognition receptors recognizing pathogen-associated molecular patterns or damage-associated molecular patterns induced by the invading bacterium. In this review, we demonstrate possible sequences of events leading to recognition of Francisella tularensis, present findings on known mechanisms for manipulating cell responses to protect Francisella from being killed, and discuss newly published data from the perspective of early stages of host-pathogen interaction.
- Klíčová slova
- Francisella tularensis, innate immune recognition, intracellular replication, phagocytosis, signaling pathways,
- MeSH
- alarminy genetika imunologie MeSH
- bakteriální proteiny genetika imunologie MeSH
- fagocytóza genetika MeSH
- Francisella tularensis genetika imunologie patogenita MeSH
- interakce hostitele a patogenu genetika imunologie MeSH
- lidé MeSH
- makrofágy imunologie mikrobiologie MeSH
- PAMP struktury imunologie metabolismus MeSH
- přirozená imunita * MeSH
- receptory buněčného povrchu genetika imunologie MeSH
- receptory rozpoznávající vzory genetika imunologie MeSH
- regulace genové exprese MeSH
- signální transdukce MeSH
- tularemie genetika imunologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- alarminy MeSH
- bakteriální proteiny MeSH
- PAMP struktury MeSH
- receptory buněčného povrchu MeSH
- receptory rozpoznávající vzory MeSH
When considering the probabilistic approach to neural networks in the framework of statistical pattern recognition we assume approximation of class-conditional probability distributions by finite mixtures of product components. The mixture components can be interpreted as probabilistic neurons in neurophysiological terms and, in this respect, the fixed probabilistic description contradicts the well known short-term dynamic properties of biological neurons. By introducing iterative schemes of recognition we show that some parameters of probabilistic neural networks can be "released" for the sake of dynamic processes without disturbing the statistically correct decision making. In particular, we can iteratively adapt the mixture component weights or modify the input pattern in order to facilitate correct recognition. Both procedures are shown to converge monotonically as a special case of the well known EM algorithm for estimating mixtures.
- MeSH
- algoritmy MeSH
- lidé MeSH
- nervová síť * MeSH
- neuronové sítě * MeSH
- neurony fyziologie MeSH
- rozpoznávání (psychologie) * MeSH
- rozpoznávání automatizované MeSH
- rozpoznávání obrazu fyziologie MeSH
- statistické modely * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The existence of pattern recognition receptors (PRRs) on immune cells was discussed in 1989 by Charles Janeway, Jr., who proposed a general concept of the ability of PRRs to recognize and bind conserved molecular structures of microorganisms known as pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, PRRs trigger intracellular signaling cascades resulting in the expression of various proinflammatory molecules. These recognition molecules represent an important and efficient innate immunity tool of all organisms. As invertebrates lack the instruments of the adaptive immune system, based on "true" lymphocytes and functional antibodies, the importance of PRRs are even more fundamental. In the present review, the structure, specificity, and expression profiles of PRRs characterized in annelids are discussed, and their role in innate defense is suggested.
- Klíčová slova
- Annelida, CCF, Discrimination, Earthworm, Immunity, LBP, PAMP, PRR, Phenoloxidase cascade, TLR,
- MeSH
- kroužkovci imunologie MeSH
- membránové glykoproteiny chemie genetika metabolismus MeSH
- PAMP struktury imunologie metabolismus MeSH
- přirozená imunita * MeSH
- proteiny akutní fáze chemie genetika metabolismus MeSH
- receptory rozpoznávající vzory chemie genetika metabolismus MeSH
- regulace genové exprese MeSH
- signální transdukce imunologie MeSH
- tkáňová distribuce MeSH
- toll-like receptory chemie genetika metabolismus MeSH
- transportní proteiny chemie genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- lipopolysaccharide-binding protein MeSH Prohlížeč
- membránové glykoproteiny MeSH
- PAMP struktury MeSH
- proteiny akutní fáze MeSH
- receptory rozpoznávající vzory MeSH
- toll-like receptory MeSH
- transportní proteiny MeSH
Pattern-recognition receptors (PRRs) recognize pathogen-associated molecular patterns and play an important role in triggering innate immune responses. PRRs distribution and function is well documented in mice and humans, but studies in pigs are scarce. Salmonella enterica serovar Typhimurium is common pathogen found in pigs and was used as a model for interaction with PRRs. This study investigated expression of PRRs in porcine leukocyte subpopulations at the mRNA level. Eight subpopulations of leukocytes comprising NK cells, Th, Tc, double positive T cells and γδ T cells, B cells, monocytes and neutrophils were sorted, and the expression of 12 PRRs was measured, including selected Toll-like receptors and their co-receptors, NOD-like receptor NOD2, RP-105, CD14, and dectin. The highest expression rates of most PRRs were observed in monocytes and neutrophils. The B cells expressed high levels of TLR1, TLR6, TLR9, TLR10, and RP-105. Only monocytes and γδ T cells were found to respond to Salmonella enterica serovar Typhimurium infection by intensification of PRRs expression. In Th and B cells, PRRs mRNA down-regulation was detected after infection.
- Klíčová slova
- Leukocyte, Pattern-recognition receptors, Pig, Salmonella, Toll-like receptors,
- MeSH
- down regulace MeSH
- leukocyty metabolismus mikrobiologie MeSH
- messenger RNA genetika MeSH
- neutrofily metabolismus MeSH
- prasata MeSH
- přirozená imunita MeSH
- receptory rozpoznávající vzory genetika metabolismus MeSH
- regulace genové exprese imunologie MeSH
- Salmonella typhimurium fyziologie MeSH
- salmonelová infekce u zvířat imunologie MeSH
- séroskupina MeSH
- T-lymfocyty metabolismus MeSH
- toll-like receptory genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- messenger RNA MeSH
- receptory rozpoznávající vzory MeSH
- toll-like receptory MeSH
T cell receptor (TCR) recognition of foreign peptides presented by major histocompatibility complex protein is a major event in triggering the adaptive immune response to pathogens or cancer. The prediction of TCR-peptide interactions has great importance for therapy of cancer as well as infectious and autoimmune diseases but remains a major challenge, particularly for novel (unseen) peptide epitopes. Here we present TCRen, a structure-based method for ranking candidate unseen epitopes for a given TCR. The first stage of the TCRen pipeline is modeling of the TCR-peptide-major histocompatibility complex structure. Then a TCR-peptide residue contact map is extracted from this structure and used to rank all candidate epitopes on the basis of an interaction score with the target TCR. Scoring is performed using an energy potential derived from the statistics of TCR-peptide contact preferences in existing crystal structures. We show that TCRen has high performance in discriminating cognate versus unrelated peptides and can facilitate the identification of cancer neoepitopes recognized by tumor-infiltrating lymphocytes.
- MeSH
- epitopy T-lymfocytární imunologie chemie MeSH
- epitopy imunologie chemie MeSH
- hlavní histokompatibilní komplex imunologie MeSH
- konformace proteinů MeSH
- lidé MeSH
- molekulární modely MeSH
- nádory imunologie MeSH
- peptidy imunologie chemie MeSH
- receptory antigenů T-buněk * imunologie chemie metabolismus MeSH
- tumor infiltrující lymfocyty imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- epitopy T-lymfocytární MeSH
- epitopy MeSH
- peptidy MeSH
- receptory antigenů T-buněk * MeSH
Nowadays, functionalization of the plasmon-supported nanostructured surface is considered as a powerful tool for tumour cell recognition. In this study, the SERS on a surface plasmon polariton-supported gold grating functionalized with folic acid was used to demonstrate an unpretentious recognition of melanoma-associated fibroblasts. Using cultivation media conditioned by different cells, we were able to detect reproducible differences in the secretome of melanoma-associated and normal control fibroblasts. The homogeneous distribution of plasmon energy along the grating surface was proved to provide excellent SERS signal reproducibility, while, to increase the affinity of (bio)molecules to SERS substrate, folic acid molecules were covalently grafted to the gold gratings. As proof of concept, fibroblasts were cultured in vitro, and culture media from the normal and tumour-associated lines were collected and analysed with our proposed SERS substrates. Identifying individual peaks of the Raman spectra as well as comparing their relative intensities, we showed that the proposed functional SERS platform can recognise the melanoma-associated cells without the need for further statistical spectral evaluation directly. We also demonstrated that the SERS chip created provided a stable SERS signal over a period of 90 days without loss of sensitivity. Graphical abstract.
- Klíčová slova
- Cancer, Melanoma, Reproducibility of SERS, SERS sensor, Surface modification,
- MeSH
- fibroblasty asociované s nádorem chemie patologie MeSH
- kovové nanočástice chemie MeSH
- kultivované buňky MeSH
- kyselina listová chemie MeSH
- lidé MeSH
- melanom chemie patologie MeSH
- nádorové buňky kultivované MeSH
- povrchové vlastnosti MeSH
- Ramanova spektroskopie metody MeSH
- zlato chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kyselina listová MeSH
- zlato MeSH
This paper describes the preparation and use of conjugates of porphyrins and bile acids as ligands to bind to tumor expressed saccharides. Bile acid-porphyrin conjugates were tested for recognition of saccharides that are typically present on malignant tumor cells. Fluorescence microscopy, in vitro PDT cell killing, and PDT of subcutaneous 4T1 mouse tumors is reported. High selectivity for saccharide cancer markers and cancer cells was observed. This in vivo and in vitro study demonstrated high potential use for these compounds in targeted photodynamic therapy.
- MeSH
- apoptóza účinky léků MeSH
- buněčné linie MeSH
- buňky 3T3 MeSH
- fluorescenční mikroskopie metody MeSH
- fotochemoterapie metody MeSH
- fragmentace DNA účinky léků MeSH
- glykosylace MeSH
- HeLa buňky MeSH
- lidé MeSH
- ligandy MeSH
- molekulární struktura MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nádorové biomarkery analýza MeSH
- nádory diagnóza farmakoterapie MeSH
- porfyriny chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- roztoky chemie MeSH
- sacharidy chemie MeSH
- screeningové testy protinádorových léčiv MeSH
- senzitivita a specificita MeSH
- transformované buněčné linie MeSH
- vazebná místa MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- žlučové kyseliny a soli chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ligandy MeSH
- nádorové biomarkery MeSH
- porfyriny MeSH
- roztoky MeSH
- sacharidy MeSH
- žlučové kyseliny a soli MeSH
In the present study, the effect of the medial septal (MS) lesions on exploratory activity in the open field and the spatial and object recognition memory has been investigated. This experiment compares three types of MS lesions: electrolytic lesions that destroy cells and fibers of passage, neurotoxic - ibotenic acid lesions that spare fibers of passage but predominantly affect the septal noncholinergic neurons, and immunotoxin - 192 IgG-saporin infusions that only eliminate cholinergic neurons. The main results are: the MS electrolytic lesioned rats were impaired in habituating to the environment in the repeated spatial environment, but rats with immuno- or neurotoxic lesions of the MS did not differ from control ones; the MS electrolytic and ibotenic acid lesioned rats showed an increase in their exploratory activity to the objects and were impaired in habituating to the objects in the repeated spatial environment; rats with immunolesions of the MS did not differ from control rats; electrolytic lesions of the MS disrupt spatial recognition memory; rats with immuno- or neurotoxic lesions of the MS were normal in detecting spatial novelty; all of the MS-lesioned and control rats clearly reacted to the object novelty by exploring the new object more than familiar ones. Results observed across lesion techniques indicate that: (i) the deficits after nonselective damage of MS are limited to a subset of cognitive processes dependent on the hippocampus, (ii) MS is substantial for spatial, but not for object recognition memory - the object recognition memory can be supported outside the septohippocampal system; (iii) the selective loss of septohippocampal cholinergic or noncholinergic projections does not disrupt the function of the hippocampus to a sufficient extent to impair spatial recognition memory; (iv) there is dissociation between the two major components (cholinergic and noncholinergic) of the septohippocampal pathway in exploratory behavior assessed in the open field - the memory exhibited by decrements in exploration of repeated object presentations is affected by either electrolytic or ibotenic lesions, but not saporin.
- MeSH
- bludiště - učení účinky léků fyziologie MeSH
- hipokampus účinky léků patologie fyziologie MeSH
- imunotoxiny toxicita MeSH
- krysa rodu Rattus MeSH
- neurotoxiny toxicita MeSH
- pátrací chování účinky léků fyziologie MeSH
- potkani Wistar MeSH
- rozpoznávání (psychologie) účinky léků fyziologie MeSH
- septální jádra účinky léků patologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- imunotoxiny MeSH
- neurotoxiny MeSH
In the last few years, classification of cells by machine learning has become frequently used in biology. However, most of the approaches are based on morphometric (MO) features, which are not quantitative in terms of cell mass. This may result in poor classification accuracy. Here, we study the potential contribution of coherence-controlled holographic microscopy enabling quantitative phase imaging for the classification of cell morphologies. We compare our approach with the commonly used method based on MO features. We tested both classification approaches in an experiment with nutritionally deprived cancer tissue cells, while employing several supervised machine learning algorithms. Most of the classifiers provided higher performance when quantitative phase features were employed. Based on the results, it can be concluded that the quantitative phase features played an important role in improving the performance of the classification. The methodology could be valuable help in refining the monitoring of live cells in an automated fashion. We believe that coherence-controlled holographic microscopy, as a tool for quantitative phase imaging, offers all preconditions for the accurate automated analysis of live cell behavior while enabling noninvasive label-free imaging with sufficient contrast and high-spatiotemporal phase sensitivity.
- Klíčová slova
- cell morphology, classification, coherence-controlled holographic microscopy, digital holographic microscopy, quantitative phase imaging, supervised machine learning,
- MeSH
- algoritmy MeSH
- buňky klasifikace cytologie MeSH
- holografie metody MeSH
- lidé MeSH
- mikroskopie metody MeSH
- rozpoznávání automatizované MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Several of today's cancer treatments are based on the immune system's capacity to detect and destroy cells expressing neoantigens on major histocompatibility class-I molecules (MHC-I). Despite this, we still do not know the cell biology behind how antigenic peptide substrates (APSs) for the MHC-I pathway are produced. Indeed, there are few research fields with so many divergent views as the one concerning the source of APSs. This is quite remarkable considering their fundamental role in the immune systems' capacity to detect and destroy virus-infected or transformed cells. A better understanding of the processes generating APSs and how these are regulated will shed light on the evolution of self-recognition and provide new targets for therapeutic intervention. We discuss the search for the elusive source of MHC-I peptides and highlight the cell biology that is still missing to explain how they are synthesised and where they come from.
- MeSH
- antigeny * MeSH
- lidé MeSH
- MHC antigeny I. třídy * MeSH
- peptidy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antigeny * MeSH
- MHC antigeny I. třídy * MeSH
- peptidy MeSH