The emotion of disgust plays a key role in the behavioral immune system, a set of disease-avoidance processes constituting a frontline defense against pathogenic threats. In the context of growing research interest in disgust, as well as recognition of its role in several psychiatric disorders, there is need for an improved understanding of behavioral triggers of disgust and for adequate techniques to both induce disgust in experimental settings and to measure individual variability in disgust sensitivity. In this study, we sought to address these issues using a multi-stage, bottom-up approach that aimed first to determine the most widespread and effective elicitors of disgust across several cultures. Based on exploratory factor analysis of these triggers, revealing four main components of pathogen-related disgust, we then generated a novel visual stimulus set of 20 images depicting scenes of highly salient pathogen risk, along with paired control images that are visually comparable but lack the disgust trigger. We present a series of validation analyses comparing our new stimulus set (the Culpepper Disgust Image Set, C-DIS) with the most commonly used pre-existing set, a series of 7 images devised by Curtis et al. (2004). Disgust scores from participants who rated the two image sets were positively correlated, indicating cross-test concordance, but results also showed that our pathogen-salient images elicited higher levels of disgust and our control images elicited lower levels of disgust. These findings suggest that the novel image set is a useful and effective tool for use in future research, both in terms of priming disgust and for measuring individual differences in disgust sensitivity.

• Klíčová slova
• disgust images, disgust prime, disgust scale, disgust sensitivity, visual stimuli,
• Publikační typ
• časopisecké články MeSH

Allergic diseases, atopy, bronchial asthma and chronic obstructive bronchitis are diseases which can directly or indirectly be traced to changes in the function of the immune system. Epidemiological studies have shown that these allergic diseases have increased in the course of time and that the incidence of obstruction of the respiratory system is clearly higher in polluted regions than in comparable control areas. These diseases are mainly the result of a comprehensive influence on the immune system. The present study describes the influence of pollutants on the behavior of cytokines which cannot be directly traced to an allergen or antigen in order to be able to explain various immunological or pseudo-allergic processes. We have isolated and cultivated PBMC from six donors and exposed them to different concentrations (5, 25, 50 and 100 mumol) of cadmium chloride. After incubation of cells with cadmium, different genes of cytokines were detected on the basis of mRNA by RT-PCR. Hsp70 can be detected in a relatively brief period following stress and there is an excellent correlation between heavy metal dose (stress) and expression of hsp70. In the case of IL-1, and TNF-alpha low concentrations of cadmium chloride increase the expression of these genes, whereas this effect is less noticeable with higher amounts of cadmium. After only one hour of exposure to heavy metals, large volumes of mRNA of IL-6 have been detected. IFN-gamma only reacts at high concentrations of cadmium. Heavy metals may influence immunocompetent cells so that they release several cytokines which may act on a large variety of cells in terms of a proinflammatory reaction. The influence of cytokines as well as the pollutants themselves on fibroblasts, endothelial cells as well as macrophages explains a number of processes which cannot be explained by allergical reactions. At low concentrations, cadmium is able to stimulate the immune system, while at higher concentrations inhibitory and suppressive reactions were observed.

• MeSH
• aktivace lymfocytů účinky léků   MeSH
• buněčná diferenciace účinky léků   imunologie   MeSH
• chlorid kademnatý farmakologie   toxicita   MeSH
• cytokiny fyziologie   MeSH
• dospělí MeSH
• imunitní systém účinky léků   MeSH
• interferon gama genetika   MeSH
• interleukin-1 fyziologie   MeSH
• interleukin-6 fyziologie   MeSH
• látky znečišťující životní prostředí farmakologie   toxicita   MeSH
• lidé MeSH
• messenger RNA biosyntéza   účinky léků   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proteiny tepelného šoku HSP70 metabolismus   MeSH
• regulace genové exprese účinky léků   imunologie   MeSH
• techniky in vitro MeSH
• TNF-alfa fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chlorid kademnatý MeSH
• cytokiny MeSH
• interferon gama MeSH
• interleukin-1 MeSH
• interleukin-6 MeSH
• látky znečišťující životní prostředí MeSH
• messenger RNA MeSH
• proteiny tepelného šoku HSP70 MeSH
• TNF-alfa MeSH

The literature data assembled in this article document the variation of immunobiological effects of nitric oxide (NO). A number of factors are obviously responsible for the diversity, ranging from inactivity, alleviation, but not rarely to exacerbation of certain pathogenetic processes. A better understanding of NO interactions with the immune system can only be reached if more complex experimental designs to study the effects of reactive nitrogen species are adopted in the future. They should integrate major participating variables and take into account pharmacodynamic/kinetic aspects of NO production in triggering the ultimate effects. If manipulation of NO in the organism by means of recently developed NO inhibitors and NO donors is to become a rational tool of immunopharmacological strategies, detailed knowledge of their pharmacologies and toxicologies is urgently needed in order to differentiate between the effects of NO and other side effects. Hopefully, this approach could improve the predictability of the clinical outcomes of NO manipulation.

• MeSH
• apoptóza MeSH
• arginin metabolismus   MeSH
• autoimunitní nemoci metabolismus   MeSH
• cytokiny fyziologie   MeSH
• cytotoxicita imunologická účinky léků   MeSH
• donory oxidu dusnatého farmakologie   MeSH
• druhová specificita MeSH
• encefalomyelitida autoimunitní experimentální metabolismus   MeSH
• endotoxemie metabolismus   MeSH
• idiopatické střevní záněty metabolismus   MeSH
• imunitní systém účinky léků   fyziologie   MeSH
• infekce metabolismus   MeSH
• izoenzymy antagonisté a inhibitory   metabolismus   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• MHC antigeny II. třídy biosyntéza   imunologie   MeSH
• myši MeSH
• nádory krevní zásobení   metabolismus   prevence a kontrola   terapie   MeSH
• oxid dusnatý farmakologie   fyziologie   MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• arginin MeSH
• cytokiny MeSH
• donory oxidu dusnatého MeSH
• izoenzymy MeSH
• MHC antigeny II. třídy MeSH
• oxid dusnatý MeSH
• synthasa oxidu dusnatého MeSH

A conceptually new bimodal immunoradiotherapy treatment was demonstrated using thermoresponsive polymer β-glucan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline) bearing complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with yttrium-90(III) at the graft ends. The behavior of this thermoresponsive polymer in aqueous solutions was studied, and it showed the appropriate cloud point temperature for brachytherapy applications. The polymer was tested in vitro, and it exhibited nontoxicity and active uptake into cancer cells and macrophages with colocalization in the lysosomes and macrophagosomes. Moreover, the observed oxidative burst response of the leukocytes established the immunostimulatory properties of the polymer, which were also studied in vivo after injection into the thigh muscles of healthy mice. The subsequent histological evaluation revealed the extensive immune activation reactions at the site of injection. Furthermore, the production of tumor necrosis factor α induced by the prepared polymer was observed in vitro, denoting the optimistic prognosis of the treatment. The biodistribution study in vivo indicated the formation of the polymer depot, which was gradually degraded and excluded from the body. The radiolabeled polymer was used during in vivo antitumor efficiency experiments on mice with EL4 lymphoma. The immunoradiotherapy group (treated with the radiolabeled polymer) demonstrated the complete inhibition of tumor growth during the beginning of the treatment. Moreover, 7 of the 15 mice were completely cured in this group, while the others exhibited significantly prolonged survival time compared to the control group. The in vivo experiments indicated the considerable synergistic effect of using immunoradiotherapy compared to separately using immunotherapy or radiotherapy.

• Klíčová slova
• Immunotherapy, Multimodal cancer therapy, Polyoxazoline, Radiotherapy, β-glucan,
• MeSH
• antibakteriální látky chemická syntéza   farmakologie   MeSH
• aza sloučeniny chemie   MeSH
• beta-glukany chemie   MeSH
• brachyterapie metody   MeSH
• heterocyklické sloučeniny monocyklické chemie   MeSH
• imunitní systém účinky léků   MeSH
• komplexní sloučeniny chemie   MeSH
• leukocyty účinky léků   metabolismus   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• nádorové buněčné linie MeSH
• oxazoly chemie   MeSH
• oxidace-redukce MeSH
• polymery chemie   MeSH
• protinádorové látky chemická syntéza   farmakologie   terapeutické užití   MeSH
• radioimunoterapie metody   MeSH
• radioizotopy ytria chemie   MeSH
• Staphylococcus aureus účinky léků   MeSH
• teplota MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid MeSH Prohlížeč
• antibakteriální látky MeSH
• aza sloučeniny MeSH
• beta-glukany MeSH
• heterocyklické sloučeniny monocyklické MeSH
• komplexní sloučeniny MeSH
• oxazoly MeSH
• polymery MeSH
• protinádorové látky MeSH
• radioizotopy ytria MeSH
• Yttrium-90 MeSH Prohlížeč

The presented classification is based on the modern view to the process of phagocytosis as evenements involving ligand-receptor interaction, transmission of signal through second messenger systems and activation of effector mechanisms leading to the specific cell behavior. According proposed classification, the phagocytic disorders are divided into extracellular disorders which are caused by abnormalities affecting ligands, and cellular disorders caused by pathological process affecting the phagocytic cell. These cellular disorders are subdivided into the defects of membrane receptors, the defects of enzymatic equipment and of subcellular structures. Laboratory investigation of phagocytic cells using several tests make possible to classify inborn, acquired, permanent as well as transient disorders into these groups. Examples of disorders in the each group are presented. This classification helps to clinicians make both diagnostic and therapeutic decisions.

• MeSH
• fagocytóza * MeSH
• lidé MeSH
• nemoci imunitního systému klasifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

The physiological changes in response to beak trimming and spectacle usage as antipecking measures were monitored in 10-mo-old common pheasants (Phasianus colchicus). Short-term analysis conducted before the beginning of the laying period showed immediate increases of plasma corticosterone (P < 0.05) and lactate dehydrogenase (P < 0.001) concentrations and decrease of plasma triglycerides (P < 0.01) levels in response to both beak trimming and the application of spectacles. Beak-trimmed pheasants exhibited higher plasma corticosterone concentrations than pheasants fitted with spectacles (P < 0.001). To assess long-term changes, blood samples for biochemical (neopterin and biopterin determination) and hematological (leukocyte profile determination) examinations were taken from beak-trimmed, spectacles-fitted, and control pheasant hens housed in cages during their laying period. At the end of the laying period, hens fitted with spectacles exhibited lower concentrations of plasma neopterin (P = 0.005) and biopterin (P = 0.005) than beak-trimmed pheasant hens. Our findings suggest that the immune system was suppressed in spectacles-fitted pheasant hens as a result of chronic stress, as also indicated by the higher heterophil-to-lymphocyte ratio (P = 0.001) compared with beak-trimmed hens. Our study found a negative correlation (r = -0.31, P = 0.019) between the heterophil-to-lymphocyte ratio and plasma neopterin concentration. This study demonstrated that both beak trimming and use of spectacles are not only stressful procedures for pheasants, but long-term effects may also include a negative impact on the immune system.

• MeSH
• agrese fyziologie   MeSH
• biologické markery MeSH
• chování zvířat fyziologie   MeSH
• fyziologický stres MeSH
• Galliformes krev   imunologie   MeSH
• leukocyty fyziologie   MeSH
• pteriny krev   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• pteriny MeSH

Many leukemia patients suffer from dysregulation of their immune system, making them more susceptible to infections and leading to general weakening (cachexia). Both adaptive and innate immunity are affected. The fruit fly Drosophila melanogaster has an innate immune system, including cells of the myeloid lineage (hemocytes). To study Drosophila immunity and physiology during leukemia, we established three models by driving expression of a dominant-active version of the Ras oncogene (RasV12 ) alone or combined with knockdowns of tumor suppressors in Drosophila hemocytes. Our results show that phagocytosis, hemocyte migration to wound sites, wound sealing, and survival upon bacterial infection of leukemic lines are similar to wild type. We find that in all leukemic models the two major immune pathways (Toll and Imd) are dysregulated. Toll-dependent signaling is activated to comparable extents as after wounding wild-type larvae, leading to a proinflammatory status. In contrast, Imd signaling is suppressed. Finally, we notice that adult tissue formation is blocked and degradation of cell masses during metamorphosis of leukemic lines, which is akin to the state of cancer-dependent cachexia. To further analyze the immune competence of leukemic lines, we used a natural infection model that involves insect-pathogenic nematodes. We identified two leukemic lines that were sensitive to nematode infections. Further characterization demonstrates that despite the absence of behavioral abnormalities at the larval stage, leukemic larvae show reduced locomotion in the presence of nematodes. Taken together, this work establishes new Drosophila models to study the physiological, immunological, and behavioral consequences of various forms of leukemia.

• Klíčová slova
• Genetics of Immunity, Ras, hemocyte, insect immunity, nematodes, oncogene,
• MeSH
• Drosophila MeSH
• fenotyp * MeSH
• hemocyty imunologie   MeSH
• kachexie * genetika   imunologie   MeSH
• larva genetika   imunologie   MeSH
• leukemie * genetika   imunologie   MeSH
• modely nemocí na zvířatech MeSH
• přirozená imunita * MeSH
• proteiny Drosophily genetika   imunologie   MeSH
• protoonkogenní proteiny p21(ras) genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny Drosophily MeSH
• protoonkogenní proteiny p21(ras) MeSH

The immune reactivity of stainless steel welders (n = 22-53) was evaluated in a three year's study. The results (phagocytic activity, cellular and humoral immunity) were statistically compared with those in control group of non-exposed persons from the same plant (n = 14-23) and with long-term laboratory reference values (LRV) (n = 14-311). In welders several changes were found when compared to the LRV: in humoral response there were higher prealbumin, lysozyme, circulating immune complexes and lower IgG. In phagocytic tests there were lower ingestion, bactericidal activity and higher metabolic activity of peripheral mononuclear leucocytes. In cellular immunity the marked lymphocytosis, higher counts of T-lymphocytes, CD4+ and CD8+ lymphocytes were noticed. After lowering the concentrations of metals in the working area there were trends to normal values in some parameters [relative numbers of T-lymphocytes, relative number of CD4+ lymphocytes, phagocytic activity, metabolic activity of leucocytes (INT index), IgA, complement C3, transferrin]. The extent and the length of the exposure to welding fumes, smoking and changed conditions at working place were followed as well.

• MeSH
• chrom moč   MeSH
• dospělí MeSH
• imunitní systém imunologie   zranění   MeSH
• kouření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci z povolání chemicky indukované   MeSH
• nikl moč   MeSH
• ocel škodlivé účinky   MeSH
• pracovní expozice škodlivé účinky   MeSH
• svařování * MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• chrom MeSH
• nikl MeSH
• ocel MeSH

The critical role of the immune system in brain function and dysfunction is well recognized, yet development of immune therapies for psychiatric diseases has been slow due to concerns about iatrogenic immune deficiencies. These concerns are emphasized by the lack of objective diagnostic tools in psychiatry. A promise to resolve this conundrum lies in the exploitation of extracellular vesicles (EVs) that are physiologically produced or can be synthetized. EVs regulate recipient cell functions and offer potential for EVs-based therapies. Intranasal EVs administration enables the targeting of specific brain regions and functions, thereby facilitating the design of precise treatments for psychiatric diseases. The development of such therapies requires navigating four dynamically interacting networks: neuronal, glial, immune, and EVs. These networks are profoundly influenced by brain fluid distribution. They are crucial for homeostasis, cellular functions, and intercellular communication. Fluid abnormalities, like edema or altered cerebrospinal fluid (CSF) dynamics, disrupt these networks, thereby negatively impacting brain health. A deeper understanding of the above-mentioned four dynamically interacting networks is vital for creating diagnostic biomarker panels to identify distinct patient subsets with similar neuro-behavioral symptoms. Testing the functional pathways of these biomarkers could lead to new therapeutic tools. Regulatory approval will depend on robust preclinical data reflecting progress in these interdisciplinary areas, which could pave the way for the design of innovative and precise treatments. Highly collaborative interdisciplinary teams will be needed to achieve these ambitious goals.

• Klíčová slova
• extracellular vesicle-based therapies, extracellular vesicles, immune system, neurological and psychiatric disorders, pharmacodynamics, pharmacokinetics, regulatory agencies,
• MeSH
• biologické markery MeSH
• duševní poruchy * terapie   imunologie   metabolismus   MeSH
• extracelulární vezikuly * imunologie   metabolismus   transplantace   MeSH
• individualizovaná medicína * metody   MeSH
• lidé MeSH
• mezibuněčná komunikace MeSH
• mozek imunologie   metabolismus   MeSH
• neuroglie * metabolismus   imunologie   MeSH
• neurony * metabolismus   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH

Integrated behavioral paradigms such as nociceptive processing coupled to anti-nociceptive responsiveness include systemically-mediated states of alertness, vigilance, motivation, and avoidance. Within a historical and cultural context, opium and its biologically active compounds, codeine and morphine, have been widely used as frontline anti-nociceptive agents. In eukaryotic cells, opiate alkaloids and opioid peptides were evolutionarily fashioned as regulatory factors in neuroimmune, vascular immune, and systemic immune communication and auto-immunoregulation. The significance of opioidergic regulation of immune function was validated by the identification of novel μ and δ opioid receptors on circulating leukocytes. The novel μ3 opioid receptor subtype has been characterized as an opioid peptide-insensitive and opiate alkaloid-selective G protein-coupled receptor (GPCR) that is functionally linked to the activation of constitutive nitric oxide synthase (cNOS). Opioid peptides stimulate granulocyte and immunocyte activation and chemotaxis via activation of a novel leukocyte δ2 receptor subtype. However, opiate alkaloid μ3 receptor agonists inhibit these same cellular activities. Opiate coupling to cNOS and subsequent production and release of mitochondrial nitric oxide (NO) suggests an evolutionary linkage to similar physiological events in prokaryotic cells. A subpopulation of immunocytes from Mytilus edulis and Leucophaea maderae and human granulocytes respond to low opioid concentrations, mediated by the adherence-promoting role of (D-Ala2-D-Met5)-enkephalinamide (DAMA), which is blocked by naloxone in a dose-dependent manner. Neutral endopeptidase 24.11 (NEP), or enkephalinase (CD10), is present on both human and invertebrate immunocytes. Alkaloids, including morphine, are found in both prokaryotic and eukaryotic cells and may have evolved much later in evolution through horizontal gene transfer. It is possible that opioid-mediated regulatory activities were conserved and elaborated during evolution as the central nervous system (CNS) became immunologically isolated by the blood-brain barrier. Thus, opioid receptor coupling became significant for cognitive and behavioural processes. Although opioid peptides and alkaloids work synergistically to suppress nociception, they mediate different actions in immune surveillance. Increased understanding of the evolutionary development of opioid receptors, nociceptive and anti-nociceptive pathways, and immunomodulation may help in the understanding of the development of tolerance to the clinical use of opiates for pain management. The significance of endogenous morphine's importance to evolution can be ascertained by the number of physiological tissues and systems that can be affected by this chemical messenger mechanism, which transcends pain. An integrated review is presented of opioid and opiate receptors, immunomodulation, and pain associated with inflammation, from an evolutionary perspective.

• Klíčová slova
• Behavior, Immunomodulation, Inflammation, Mitochondria, Nitric Oxide, Opiate, Opioid, Opioid receptors, Pain,
• MeSH
• biologická evoluce MeSH
• bolest metabolismus   MeSH
• chování MeSH
• imunita MeSH
• imunomodulace MeSH
• lidé MeSH
• morfin metabolismus   MeSH
• opioidní peptidy metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• receptory opiátové genetika   metabolismus   MeSH
• zánět metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• morfin MeSH
• opioidní peptidy MeSH
• oxid dusnatý MeSH
• receptory opiátové MeSH