Two genotypes of the intestinal parasite Ceratonova shasta infect Oncorhynchus mykiss: genotype 0 results in a chronic infection with low mortality while genotype IIR causes disease with high mortality. We determined parasite load and the relative expression of six immune factors (IgT, IgM, IL-6, IL-8, IL-10, IFNG) in fish infected with either genotype over 29 days post-exposure. In genotype IIR infections the host responded with upregulation of inflammatory and regulatory cytokines. In contrast, genotype 0 infection did not elicit an inflammatory response and expression of IFNG and IL-10 was lower. Antibody expression was upregulated in both infections but appeared to have limited efficacy in the virulent genotype IIR infections. Histologically, in genotype 0 infections the parasite migrated through the tissue layers causing inflammation but minimal damage to the mucosal epithelium, which contrasts with the severe pathology found in genotype IIR infections.

• Klíčová slova
• Cytokine, Fish disease, Immunoglobulin, Intestine, Salmonid,
• MeSH
• cytokiny genetika   metabolismus   MeSH
• genotyp * MeSH
• imunoglobulin M krev   MeSH
• imunoglobuliny krev   MeSH
• interakce hostitele a parazita MeSH
• Myxozoa genetika   patogenita   MeSH
• nemoci ryb imunologie   MeSH
• Oncorhynchus mykiss imunologie   MeSH
• parazitární nemoci u zvířat imunologie   MeSH
• parazitární zátěž MeSH
• pohyb buněk MeSH
• rybí proteiny krev   MeSH
• sliznice imunologie   MeSH
• virulence MeSH
• zánět imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• cytokiny MeSH
• immunoglobulin T, teleost MeSH Prohlížeč
• imunoglobulin M MeSH
• imunoglobuliny MeSH
• rybí proteiny MeSH

Mucosal-associated invariant T (MAIT) cells are innate-like T cells comprising up to 10% of the peripheral blood T cells in humans. During ontogeny, MAIT cells can first be detected in the cord blood in low amounts, but rise steadily after birth. In this population-based study, we show that their counts continue to increase, reaching maximal levels (4.5% of CD3(+) cells, 65 cells/μl) in the third and fourth decenniums. At this age, the amounts of MAIT cells exhibit the highest interindividual variability. The values then dramatically decline; subjects 80 years old and older have on average 10 times less MAIT cells, both absolutely and as a percentage among CD3(+) T cells, than subjects in fertile age. The senescence of MAIT cells is associated with decreased CD8/double negative (DN) ratio. Finally, we observed significantly higher amounts of MAIT cells in women of reproductive age than in men of the same age. Our data suggest that further studies aimed at elucidating a role of MAIT cells in human pathologies must recruit age- and gender-matched controls.

• MeSH
• antigeny CD3 biosyntéza   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• imunologická paměť MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• počet lymfocytů MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sliznice cytologie   imunologie   MeSH
• stárnutí imunologie   MeSH
• T-lymfocyty - podskupiny imunologie   MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD3 MeSH

Although sera and all external secretions contain antibodies to human immunodeficiency virus (HIV), their levels, specificity, isotypes, and relevant effector functions display a great degree of variability. Antibodies that bind HIV antigens and neutralize the virus are predominantly associated with the IgG isotype in sera and in all external secretions, even where total levels of IgG are much lower than those of IgA. Rectal fluid that contains high IgA, but low IgG levels, displayed low neutralizing activity independent of antibodies. Therefore, external secretions should be evaluated before and after selective depletion of Ig. At the systemic level, HIV-specific IgA may interfere with the effector functions of IgG, as suggested by recent studies of individuals systemically immunized with an experimental HIV vaccine. Although HIV-specific IgG and IgA antibodies may exhibit their protective activities at mucosal surfaces through interference with viral entry and local neutralization at the systemic level, such antibodies may display discordant effector functions.

• Klíčová slova
• Antibody responses, human immunodeficiency virus, mucosal immunity, secretory IgA and IgG,
• MeSH
• HIV antigeny imunologie   MeSH
• HIV infekce imunologie   MeSH
• HIV protilátky krev   imunologie   MeSH
• HIV-1 imunologie   MeSH
• humorální imunita MeSH
• imunoglobulin A krev   imunologie   MeSH
• imunoglobulin G krev   imunologie   MeSH
• lidé MeSH
• neutralizující protilátky krev   imunologie   MeSH
• sliznice imunologie   metabolismus   virologie   MeSH
• vaginální výplach MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• HIV antigeny MeSH
• HIV protilátky MeSH
• imunoglobulin A MeSH
• imunoglobulin G MeSH
• neutralizující protilátky MeSH

Mucosal immune system is functionally characterized by its ability to limit the access of environmental antigens such as food, airborne materials, and commensal microbes to the systemic immune compartment, leading to reduction in the magnitude of systemic immune responses. Mucosal immune system reacts at the site of antigen exposure and at anatomically distant mucosal sites by specific antibodies production and specific cellular immunity. The mucosal administration of neoantigen induces specific mucosal and systemic antibodies production and systemic effector T cells anergy accompanied by induction of regulatory T cells, phenomenon termed mucosal tolerance. Based on above observations, several studies test the ability to prevent some autoimmune diseases by mucosal administration of respective antigens but with little to no success. This review attempts to describe mechanisms involved in the induction of immune response and tolerance after immunization by mucosal routes - oral or intranasal administration. Further it aims to elucidate conditions critical for elicitation of mucosal tolerance.

• MeSH
• epitopy imunologie   MeSH
• imunologická tolerance imunologie   MeSH
• lidé MeSH
• přirozená imunita imunologie   MeSH
• sliznice imunologie   MeSH
• slizniční imunita imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• epitopy MeSH

Metagenomic approaches are currently being used to decipher the genome of the microbiota (microbiome), and, in parallel, functional studies are being performed to analyze the effects of the microbiota on the host. Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization. Animals used as models of human diseases can be maintained in sterile conditions (isolators used for germ-free rearing) and specifically colonized with defined microbes (including non-cultivable commensal bacteria). The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models. Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia (i.e., using models of human inflammatory bowel disease and colorectal carcinoma). In contrast, a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic (NOD) mice. Interestingly, the development of atherosclerosis in germ-free apolipoprotein E (ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals. Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota. Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial, disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components (e.g., probiotics and prebiotics) whose administration may aid in disease prevention and treatment.

• MeSH
• autoimunitní nemoci etiologie   mikrobiologie   MeSH
• gastrointestinální trakt mikrobiologie   MeSH
• gnotobiologické modely * MeSH
• imunita MeSH
• lidé MeSH
• metagenom imunologie   MeSH
• modely nemocí na zvířatech MeSH
• nádory etiologie   mikrobiologie   MeSH
• sliznice imunologie   MeSH
• zánět etiologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Commensal microflora (normal microflora, indigenous microbiota) consists of those micro-organisms, which are present on body surfaces covered by epithelial cells and are exposed to the external environment (gastrointestinal and respiratory tract, vagina, skin, etc.). The number of bacteria colonising mucosal and skin surfaces exceeds the number of cells forming human body. Commensal bacteria co-evolved with their hosts, however, under specific conditions they are able to overcome protective host responses and exert pathologic effects. Resident bacteria form complex ecosystems, whose diversity is enormous. The most abundant microflora is present in the distal parts of the gut; the majority of the intestinal bacteria are Gram-negative anaerobes. More than 50% of intestinal bacteria cannot be cultured by conventional microbiological techniques. Molecular biological methods help in analysing the structural and functional complexity of the microflora and in identifying its components. Resident microflora contains a number of components able to activate innate and adaptive immunity. Unlimited immune activation in response to signals from commensal bacteria could pose the risk of inflammation; immune responses to mucosal microbiota therefore require a precise regulatory control. The mucosal immune system has developed specialised regulatory, anti-inflammatory mechanisms for eliminating or tolerating non-dangerous, food and airborne antigens and commensal micro-organisms (oral, mucosal tolerance). However, at the same time the mucosal immune system must provide local defense mechanisms against environmental threats (e.g. invading pathogens). This important requirement is fulfilled by several mechanisms of mucosal immunity: strongly developed innate defense mechanisms ensuring appropriate function of the mucosal barrier, existence of unique types of lymphocytes and their products, transport of polymeric immunoglobulins through epithelial cells into secretions (sIgA) and migration and homing of cells originating from the mucosal organised tissues in mucosae and exocrine glands. The important role of commensal bacteria in development of optimally functioning mucosal immune system was demonstrated in germ-free animals (using gnotobiological techniques). Involvement of commensal microflora and its components with strong immunoactivating properties (e.g. LPS, peptidoglycans, superantigens, bacterial DNA, Hsp) in etiopathogenetic mechanism of various complex, multifactorial and multigenic diseases, including inflammatory bowel diseases, periodontal disease, rheumatoid arthritis, atherosclerosis, allergy, multiorgan failure, colon cancer has been recently suggested. Animal models of human diseases reared in defined gnotobiotic conditions are helping to elucidate the aetiology of these frequent disorders. An improved understanding of commensal bacteria-host interactions employing germ-free animal models with selective colonisation strategies combined with modern molecular techniques could bring new insights into the mechanisms of mucosal immunity and also into pathogenetic mechanisms of several infectious, inflammatory, autoimmune and neoplastic diseases. Regulation of microflora composition (e.g. by probiotics and prebiotics) offers the possibility to influence the development of mucosal and systemic immunity but it can play a role also in prevention and treatment of some diseases.

• MeSH
• autoimunitní nemoci etiologie   imunologie   MeSH
• Bacteria růst a vývoj   imunologie   MeSH
• chronická nemoc MeSH
• CpG ostrůvky imunologie   MeSH
• epitelové buňky imunologie   MeSH
• imunologická tolerance imunologie   MeSH
• kůže imunologie   mikrobiologie   MeSH
• lidé MeSH
• lipopolysacharidy imunologie   MeSH
• lymfoidní tkáň imunologie   MeSH
• peptidoglykan imunologie   MeSH
• přirozená imunita imunologie   MeSH
• proteiny tepelného šoku imunologie   MeSH
• sliznice imunologie   mikrobiologie   MeSH
• slizniční imunita imunologie   MeSH
• superantigeny imunologie   MeSH
• zánět etiologie   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• lipopolysacharidy MeSH
• peptidoglykan MeSH
• proteiny tepelného šoku MeSH
• superantigeny MeSH

The interface between the organism and the outside world, which is the site of exchange of nutrients, export of products and waste components, must be selectively permeable and at the same time, it must constitute a barrier equipped with local defense mechanisms against environmental threats (e.g. invading pathogens). The boundaries with the environment (mucosal and skin surfaces) are therefore covered with special epithelial layers which support this barrier function. The immune system, associated with mucosal surfaces covering the largest area of the body (200-300 m(2)), evolved mechanisms discriminating between harmless antigens and commensal microorganisms and dangerous pathogens. The innate mucosal immune system, represented by epithelial and other mucosal cells and their products, is able to recognize the conserved pathogenic patterns on microbes by pattern recognition receptors such as Toll-like receptors, CD14 and others. As documented in experimental gnotobiotic models, highly protective colonization of mucosal surfaces by commensals has an important stimulatory effect on postnatal development of immune responses, metabolic processes (e.g. nutrition) and other host activities; these local and systemic immune responses are later replaced by inhibition, i.e. by induction of mucosal (oral) tolerance. Characteristic features of mucosal immunity distinguishing it from systemic immunity are: strongly developed mechanisms of innate defense, the existence of characteristic populations of unique types of lymphocytes, colonization of the mucosal and exocrine glands by cells originating from the mucosal organized tissues ('common mucosal system') and preferential induction of inhibition of the responses to nondangerous antigens (mucosal tolerance). Many chronic diseases, including allergy, may occur as a result of genetically based or environmentally induced changes in mechanisms regulating mucosal immunity and tolerance; this leads to impaired mucosal barrier function, disturbed exclusion and increased penetration of microbial, food or airborne antigens into the circulation and consequently to exaggerated and generalized immune responses to mucosally occurring antigens, allergens, superantigens and mitogens.

• MeSH
• alergie imunologie   MeSH
• epitel imunologie   MeSH
• imunologická tolerance MeSH
• imunoterapie MeSH
• lidé MeSH
• sliznice imunologie   MeSH
• slizniční imunita imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The mucosal immune system is an integral part of the whole-body immune system, however its regulation, maturation and function are to a great degree independent. Mucosal lymphoid tissue is the largest immune organ of the body, that stands in the first line of defence against foreign invaders. The goal of the immune system is immunity, however immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune system, because the organism must tolerate thousands of ingested and inhaled harmless food and bacterial antigens. The phenomenon of oral tolerance is the unique feature of the mucosal immune system. If abrogated, severe autoimmune diseases like Crohn's disease, ulcerative colitis or coeliac sprue can develop. The quality of mucosal immune responses during newborn and infant age strongly influences the immune reactivity later in life. The most important factors influencing the development of mucosal immune reactivity are the feeding practices and microbial colonization. Manipulation of the mucosal immune system offers interesting possibilities to prevent infection as well as autoimmune diseases directly in the affected tissue, without participation of the whole-body immune system. In this review we present the most recent basic information about the mechanisms of mucosal immunity, ontogeny of mucosal immunity, mucosal tolerance and immunisation and the role of mucosal immunity in an inherited disease in which the main battlefield is the lung mucosa-cystic fibrosis.

• MeSH
• cystická fibróza imunologie   patofyziologie   MeSH
• imunologická tolerance MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• sliznice růst a vývoj   imunologie   MeSH
• slizniční imunita imunologie   fyziologie   MeSH
• vakcinace * MeSH
• vývoj dítěte MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The non-pathogenic, non-colonising Gram-positive organism Lactobacillus lactis is beeing developed as an antigen delivery system for mucosal vaccination. A high level expression system has been developed which allows loading of the bacterium with high levels of a heterologous antigen (TTFC) prior to inoculation. Mucosal inoculation of one such recombinant strain results in a protective serum antibody response and production of TTFC-specific IgA at mucosal sites.

• MeSH
• antigeny bakteriální aplikace a dávkování   genetika   MeSH
• genetické vektory MeSH
• Lactococcus lactis genetika   imunologie   MeSH
• peptidové fragmenty aplikace a dávkování   genetika   imunologie   MeSH
• protilátky bakteriální biosyntéza   MeSH
• rekombinantní proteiny aplikace a dávkování   genetika   imunologie   MeSH
• sliznice imunologie   MeSH
• syntetické vakcíny aplikace a dávkování   genetika   MeSH
• tetanový toxin aplikace a dávkování   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antigeny bakteriální MeSH
• peptidové fragmenty MeSH
• protilátky bakteriální MeSH
• rekombinantní proteiny MeSH
• syntetické vakcíny MeSH
• tetanový toxin MeSH
• tetanus toxin fragment C MeSH Prohlížeč

Presence of spontaneously produced immunoglobulins bearing a broad spectrum of "natural" antibody specificities (including autoantibodies) in sera and other body fluids results mainly from inapparent immunization and polyclonal B cell activation by microflora and food antigens occurring mostly on mucosal surfaces. Early postnatal ontogeny in external environment is characterized by rapid growth and functional maturation of secondary lymphatic tissues as a consequence of this "natural" mucosal immunization. Under normal circumstances a state of "oral" tolerance to intestinal antigens is actively established after this period. Studies performed in germ-free, antigen-free and maternal antibody-deprived animals showed that low amounts of natural antibodies (mainly of IgM isotype) are formed without any known cause of stimulation. These "nonstimulated" antibodies, similarly as hybridomas originating from nonimmunized newborns, correspond to the preimmune repertoire of antibodies characterized by poly-specificity, high connectivity and reactivity against self antigens. Together with other innate humoral and cellular factors, they probably represent the first line of anti-infectious resistance. Moreover, due to their connectivity they are supposed to play an important role in B cell repertoire shaping (forming an idiotypic network), through interaction with a broad spectrum of immunological components they act as regulatory molecules, and through their participation in catabolic events they can promote morphogenetic changes during fetal development. Beneficial therapeutic effects of nonspecific gammaglobulin (IVIG) application observed recently in patients with autoimmune diseases suggest that they can influence autoimmune reactivity by a not yet analyzed mechanism. Other functions of natural autoantibodies can be suggested and expected to be found in the near future.(ABSTRACT TRUNCATED AT 250 WORDS)

• MeSH
• autoimunita fyziologie   MeSH
• B-lymfocyty imunologie   MeSH
• přirozená imunita fyziologie   MeSH
• sliznice imunologie   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH