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The aim of this review is to provide a review of the immune system in fish, including the ontogeny, mechanisms of unspecific and acquired immunity and the action of some immunomodulators. Fish rely on their innate immune system for an extended period of time, beginning at the early stages of embryogenesis. The components of the innate immune response are divided into physical, cellular and humoral factors and include humoral and cellular receptor molecules that are soluble in plasma and other body fluids. The lymphoid organs found in fish include the thymus, spleen and kidney. Immunoglobulins are the principal components of the immune response against pathogenic organisms. Immunomodulatory products, including nucleotides, glucans and probiotics, are increasingly used in aquaculture production. The use of these products reduces the need for therapeutic treatments, enhances the effects of vaccines and, in turn, improves the indicators of production.

Glucocorticoid hormones, acting via nuclear receptors, regulate many metabolic processes, including hepatic gluconeogenesis. It recently has been recognized that intracellular glucocorticoid concentrations are determined not only by plasma hormone levels, but also by intracellular 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs), which interconvert active corticosterone (cortisol in humans) and inert 11-dehydrocorticosterone (cortisone in humans). 11 beta-HSD type 2, a dehydrogenase, thus excludes glucocorticoids from otherwise nonselective mineralocorticoid receptors in the kidney. Recent data suggest the type 1 isozyme (11 beta-HSD-1) may function as an 11 beta-reductase, regenerating active glucocorticoids from circulating inert 11-keto forms in specific tissues, notably the liver. To examine the importance of this enzyme isoform in vivo, mice were produced with targeted disruption of the 11 beta-HSD-1 gene. These mice were unable to convert inert 11-dehydrocorticosterone to corticosterone in vivo. Despite compensatory adrenal hyperplasia and increased adrenal secretion of corticosterone, on starvation homozygous mutants had attenuated activation of the key hepatic gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, presumably, because of relative intrahepatic glucocorticoid deficiency. The 11 beta-HSD-1 -/- mice were found to resist hyperglycemia provoked by obesity or stress. Attenuation of hepatic 11 beta-HSD-1 may provide a novel approach to the regulation of gluconeogenesis

Adaptive immunity depends on T-cell exit from the thymus and T and B cells travelling between secondary lymphoid organs to survey for antigens. After activation in lymphoid organs, T cells must again return to circulation to reach sites of infection; however, the mechanisms regulating lymphoid organ exit are unknown. An immunosuppressant drug, FTY720, inhibits lymphocyte emigration from lymphoid organs, and phosphorylated FTY720 binds and activates four of the five known sphingosine-1-phosphate (S1P) receptors 1 , 2 , 3 , 4 . However, the role of S1P receptors in normal immune cell trafficking is unclear. Here we show that in mice whose haematopoietic cells lack a single S1P receptor (S1P 1 ; also known as Edg1) there are no T cells in the periphery because mature T cells are unable to exit the thymus. Although B cells are present in peripheral lymphoid organs, they are severely deficient in blood and lymph. Adoptive cell transfer experiments establish an intrinsic requirement for S1P 1 in T and B cells for lymphoid organ egress. Furthermore, S1P 1 -dependent chemotactic responsiveness is strongly upregulated in T-cell development before exit from the thymus, whereas S1P 1 is downregulated during peripheral lymphocyte activation, and this is associated with retention in lymphoid organs. We find that FTY720 treatment downregulates S1P 1 , creating a temporary pharmacological S1P 1 -null state in lymphocytes, providing an explanation for the mechanism of FTY720-induced lymphocyte sequestration. These findings establish that S1P 1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.

Generation of a self-tolerant but antigen-responsive T cell repertoire occurs in the thymus. Although glucocorticoids are usually considered immunosuppressive, there is also evidence that they play a positive role in thymocyte selection. To address the question of how endogenous glucocorticoids might influence the adaptive immune response, we generated GRlck-Cre mice, in which the glucocorticoid receptor gene (GR) is deleted in thymocytes prior to selection. These mice were immunocompromised, with reduced polyclonal T cell proliferative responses to alloantigen, defined peptide antigens, and viral infection. This was not due to an intrinsic proliferation defect, because GR-deficient T cells responded normally when the TCR was cross-linked with antibodies or when the T cell repertoire was \"fixed\" with αβ TCR transgenes. Varying the affinity of self ligands in αβ TCR transgenic mice showed that affinities that would normally lead to thymocyte-positive selection caused negative selection, and alterations in the TCR repertoire of polyclonal T cells were confirmed by analysis of TCR Vβ CDR3 regions. Thus, endogenous glucocorticoids are required for a robust adaptive immune response because of their promotion of the selection of T cells that have sufficient affinity for self, and the absence of thymocyte glucocorticoid signaling results in an immunocompromised state.

In birds and mammals T cells develop along two discrete pathways characterized by expression of either the alpha beta or the gamma delta T-cell antigen receptors (TCRs). To gain further insight into the evolutionary significance of the gamma delta T-cell lineage, the present studies sought to define the chicken TCR gamma locus. A splenic cDNA library was screened with two polymerase chain reaction products obtained from genomic DNA using primers for highly conserved regions of TCR and immunoglobulin genes. This strategy yielded cDNA clones with characteristics of mammalian TCR gamma chains, including canonical residues considered important for proper folding and stability. Northern blot analysis with the TCR gamma cDNA probe revealed 1.9-kb transcripts in the thymus, spleen, and a gamma delta T-cell line, but not in B or alpha beta T-cell lines. Three multimember V gamma subfamilies, three J gamma gene segments, and a single constant region C gamma gene were identified in the avian TCR gamma locus. Members of each of the three V gamma subfamilies were found to undergo rearrangement in parallel during the first wave of thymocyte development. TCR gamma repertoire diversification was initiated on embryonic day 10 by an apparently random pattern of V-J gamma recombination, nuclease activity, and P- and N-nucleotide additions to generate a diverse repertoire of avian TCR gamma genes early in ontogeny

Our earlier studies have shown that retrovirus insertion into herpesvirus is an efficient process that engenders recombinant herpesviruses with altered biological properties. The RM1 clone is derived from the JM strain of Marek's disease virus (MDV) through retrovirus insertional mutagenesis and contains sequences of reticuloendotheliosis virus inserted at the junction of the internal repeat and unique short regions of the genome. In previous studies, the RM1 clone appeared attenuated for oncogenicity but caused marked atrophy of the thymic lobes. The present studies represent a detailed analysis of the biological characteristics of the RM1 clone in order to better understand mechanisms of oncogenicity and gene function of MDV. RM1 was almost fully attenuated for oncogenicity but retained other in vivo properties of virulent viruses such as thymic and bursal atrophy, early immunosuppression, early cytolytic infection followed by efficient replication, and contact spread--all normally absent in attenuated strains. This suggests that, for serotype a MDV, oncogenicity is not tightly linked with immunodepression or viral replication and that these properties may be controlled by different genes or mechanisms. The mutation was stable through serial passage of the virus in chickens as determined by molecular analysis. None of the mutant viruses demonstrated expansion of the 132-bp repeat region of the genome, indicating that such expansion is not required for attenuation. Chickens vaccinated with RM1 clones were protected against challenge with virulent MDV, and levels of protection exceeded those of other attenuated serotype 1 vaccine viruses. Thus, attenuation by selective mutation may be an advantageous strategy for development of serotype 1 Marek's disease vaccines

Reaktive und neoplastische Veränderungen des Thymus stehen im Zentrum der Differenzialdiagnose bei tumorartigen Veränderungen des vorderen und mittleren Mediastinums, während bei Tumoren des hinteren Mediastinums besonders an neurogene Neoplasien zu denken ist (die hier nicht behandelt werden). Bei Neugeborenen und Säuglingen stellen Keimzelltumoren, kongenitale Zysten und „echte Thymushyperplasien“, die häufigsten Veränderungen im vorderen Mediastinum dar. Bei Kleinkindern dominieren Teratome vor Dottersacktumoren und Zysten. Bei älteren Kindern und Jugendlichen sind Lymphome am prävalentesten, während Thymuskarzinome und Thymome Raritäten sind. Zusätzlich sind dann auch entzündlich bedingt Thymushyperplasie bei Myasthenia gravis und „Überschusshyperplasien“ des Thymus z. B. nach Chemotherapie zu bedenken. Sarkome sind ab der Geburt seltene aber wichtige Differenzialdiagnosen. Ausgehend von der Schilderung eines seltenen Falls einer rezidivierten „echten Thymushyperplasie“ wird die Differenzialdiagnose dieser nichtneoplastischen aber potenziell lebensbedrohlichen Erkrankung diskutiert.

Die Immunzellen dieses Systems wie Granulozyten, Makrophagen und natürliche Killerzellen reagieren sehr schnell, in Sekunden oder Minuten nach dem Kontakt mit den Antigenen des Erregers.