Nejvíce citovaný článek - PubMed ID 6991302
Development of antibody formation in germ-free and conventionally reared rabbits: the role of intestinal lymphoid tissue in antibody formation to E. coli antigens
This brief review is dedicated to the legacy of Prof. Jaroslav Šterzl and his colleagues, who laid the foundation for gnotobiology in the former Czechoslovakia 55 years. Prof. Sterzl became one of the founders of modern Czechoslovak immunology, which was characterized by work on a wide range of problems needing to be solved. While examining the mechanisms of innate immunity, he focused his studies on the induction of antibody production by immunocompetent cells involved in adaptive immune transmission while using the model of pig fetuses and germ-free piglets and characterizing immunoglobulins in the sera of these piglets. Although not fully appreciated to this day, his experimental proof of the hypothesis focused on the common precursor of cell-forming antibodies of different isotypes was later confirmed in experiments at the gene level. Prof. Sterzl's work represented a true milestone in the development of not solely Czechoslovak but also European and global immunology. He collaborated closely with the World Health Organization for many years, serving there as leader of the Reference Laboratory for Factors of Innate Immunity.
- Klíčová slova
- Germ-free model, Gnotobiology, Host-pathogen interaction, Innate immunity, Microbiota,
- MeSH
- gnotobiologické modely * MeSH
- interakce hostitele a patogenu * MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- střevní mikroflóra MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of "molecular mimicry" (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.
- MeSH
- autoimunita imunologie MeSH
- autoimunitní nemoci etiologie imunologie MeSH
- infekce imunologie MeSH
- lidé MeSH
- myši MeSH
- střevní sliznice imunologie mikrobiologie MeSH
- syndromy imunologické nedostatečnosti imunologie MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The aim of the study was to compare the phenotype of lymphocyte subpopulations of the GALT (gut-associated lymphatic tissue) in germfree (GF) and conventionally (CV) reared rats, i.e. to analyze the effect of microbial colonization on the development of intestinal lymphocyte subsets. Surface marker characteristics were studied in cell suspensions isolated from Peyer's patches, mesenteric lymph nodes, spleen and the intraepithelial lymphocyte compartment of 2- and 12-month old inbred AVN rats. The pattern of T lymphocyte phenotypes in Peyer's patches, mesenteric lymph nodes and spleen determined by FACS analysis did not reveal differences between GF and CV rats. In contrast, a 2-month conventionalization of GF rats led to substantial changes in the composition of intestinal intraepithelial lymphocyte subsets (IELs): increase of CD4+, CD8 alpha+, CD8 beta+, TcR alpha/beta+ bearing lymphocytes was observed after colonization of rats with normal microflora. Surprisingly, the relative numbers of lymphocytes bearing TcR gamma/delta+ did not change during conventionalization. The effect of aging was also studied and differences in IELs composition of aged (GF) and (CV) rats were found to be more pronounced: 6.6% and 30% of lymphocytes bearing TcR alpha/beta were present among IELs in two-month old GF and CV rats, respectively. 30% of IELs in 2-month old GF rats, 80% of IEL from 12-month old CV rats were found to bear TcR alpha/beta. This finding demonstrates that during conventionalization and aging the TcR alpha/beta bearing population of IELs substantially expands. It suggests that mainly this lymphocyte subset responds to microflora stimuli and is probably involved in the protection of the epithelial cell layer of intestinal mucosa.
- MeSH
- Bacteria růst a vývoj MeSH
- gnotobiologické modely MeSH
- imunofenotypizace MeSH
- inbrední kmeny potkanů MeSH
- krysa rodu Rattus MeSH
- lymfoidní tkáň imunologie MeSH
- stárnutí imunologie MeSH
- střevní sliznice imunologie mikrobiologie MeSH
- T-lymfocyty - podskupiny imunologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Mucosal surfaces covered by a layer of epithelial cells represent the largest and most critical interface between the organism and its environment. The barrier function of mucosal surfaces is performed by the epithelial layer and immune cells present in the mucosal compartment. As recently found, epithelial cells, apart from their participation in absorptive, digestive and secretory processes perform more than a passive barrier function and are directly involved in immune processes. Besides the well known role of epithelial cells in the transfer of polymeric immunoglobulins produced by lamina propria B lymphocytes to the luminal content of mucosals (secretory Igs), these cells were found to perform various other immunological functions, to interact with other cells of the immune system and to induce an efficient inflammatory response to microbial invasion: enzymic processing of dietary antigens, expression of class I and II MHC antigens, presentation of antigens to lymphocytes, expression of adhesive molecules mediating interaction with intraepithelial lymphocytes and components of extracellular matrix, production of cytokines and probable participation in extrathymic T cell development of intraepithelial lymphocytes. All these functions were suggested to influence substantially the mucosal immune system and its response. Under immunopathological conditions, e.g. during infections and inflammatory bowel and celiac diseases, both epithelial cells and intraepithelial lymphocytes participate substantially in inflammatory reactions. Moreover, enterocytes could become a target of mucosal immune factors. Mucosal immunosurveillance function is of crucial importance in various pathological conditions but especially in the case of the most frequent malignity occurring in the intestinal compartment, i.e. colorectal carcinoma. Proper understanding of the differentiation processes and functions of epithelial cells in interaction with other components of the mucosal immune system is therefore highly desirable.
- MeSH
- autoimunitní nemoci imunologie patologie MeSH
- Bacteria imunologie MeSH
- celiakie imunologie patologie MeSH
- cytokiny fyziologie MeSH
- dospělí MeSH
- epitel imunologie MeSH
- epitelové buňky MeSH
- houby imunologie MeSH
- idiopatické střevní záněty imunologie patologie MeSH
- imunoglobuliny imunologie MeSH
- integriny fyziologie MeSH
- kolorektální nádory imunologie patologie MeSH
- lidé MeSH
- lymfoidní tkáň cytologie imunologie MeSH
- membránové glykoproteiny fyziologie MeSH
- myši knockoutované MeSH
- myši MeSH
- Peyerovy pláty imunologie MeSH
- prezentace antigenu MeSH
- střeva mikrobiologie MeSH
- střevní sliznice cytologie imunologie MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cytokiny MeSH
- imunoglobuliny MeSH
- integriny MeSH
- membránové glykoproteiny MeSH
Lymphatic tissues of GF and CV rabbits were observed. No cells producing IgA and IgM antibodies were detected in appendix, sacculus rotundus, ileum terminale and thymus of GF rabbits. IgA cells were found in lymph nodes of GF rabbits.
- MeSH
- buňky produkující protilátky imunologie MeSH
- cytoplazma imunologie MeSH
- gnotobiologické modely * MeSH
- imunoglobulin A metabolismus MeSH
- imunoglobulin G metabolismus MeSH
- imunoglobulin M metabolismus MeSH
- králíci imunologie MeSH
- lymfoidní tkáň cytologie imunologie MeSH
- zvířata MeSH
- Check Tag
- králíci imunologie MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- imunoglobulin A MeSH
- imunoglobulin G MeSH
- imunoglobulin M MeSH