Alcoholic patients have a high incidence of hepatitis C virus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of ...Alcoholic patients have a high incidence of hepatitis C virus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability 'of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.展开更多
Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism c...Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism causing transient infections. Despite all scientific efforts, there are still some gaps in the knowledge of the pathogenesis of this disease. Antigen presenting cells(APCs), as initiators of the immune response, are located in the first line of defense against microorganisms, and are responsible for antigen recognition, processing and presentation. Dendritic cells(DCs) are the main type of APC involved in antigen presentation and they are susceptible to PRRSV infection. Thus, PRRSV replication in DCs may trigger off different mechanisms to impair the onset of a host effective immune response against the virus. On the one side, PRRSV may impair the basic functions of DCs by regulating the expression of major histocompatibility complex class Ⅱ and CD80/86. Other strategy followed by the virus is the induction of cell death of APCs by apoptosis, necrosis or both of them. The impairment and/or cell death ofAPCs could lead to a failure in the onset of an efficient immune response, as long as cells could not properly activate T cells. Future aspects to take into account are also discussed in this review.展开更多
Recent examples of periodic bifurcations in descendant trees of finite p-groups with ?are used to show that the possible p-class tower groups G of certain multiquadratic fields K with p- class group of type (2,2,2) , ...Recent examples of periodic bifurcations in descendant trees of finite p-groups with ?are used to show that the possible p-class tower groups G of certain multiquadratic fields K with p- class group of type (2,2,2) , resp. (3,3), form periodic sequences in the descendant tree of the elementary Abelian root , resp. . The particular vertex of the periodic sequence which occurs as the p-class tower group G of an assigned field K is determined uniquely by the p-class number of a quadratic, resp. cubic, auxiliary field k, associated unambiguously to K. Consequently, the hard problem of identifying the p-class tower group G is reduced to an easy computation of low degree arithmetical invariants.展开更多
Let F be a number field and p be a prime. In the successive approximation theorem, we prove that, for each integer n ≥ 1, finitely many candidates for the Galois group of the nth stage of the p-class tower over F are...Let F be a number field and p be a prime. In the successive approximation theorem, we prove that, for each integer n ≥ 1, finitely many candidates for the Galois group of the nth stage of the p-class tower over F are determined by abelian type invariants of p-class groups C1pE of unramified extensions E/F with degree [E : F] = pn-1. Illustrated by the most extensive numerical results available currently, the transfer kernels (TE, F) of the p-class extensions TE, F : C1pF → C1pE from F to unramified cyclic degree-p extensions E/F are shown to be capable of narrowing down the number of contestants significantly. By determining the isomorphism type of the maximal subgroups S G of all 3-groups G with coclass cc(G) = 1, and establishing a general theorem on the connection between the p-class towers of a number field F and of an unramified abelian p-extension E/F, we are able to provide a theoretical proof of the realization of certain 3-groups S with maximal class by 3-tower groups of dihedral fields E with degree 6, which could not be realized up to now.展开更多
Let p be a prime. For any finite p-group G, the deep transfers T H,G ' : H / H ' → G ' / G " from the maximal subgroups H of index (G:H) = p in G to the derived subgroup G ' are introduced as an ...Let p be a prime. For any finite p-group G, the deep transfers T H,G ' : H / H ' → G ' / G " from the maximal subgroups H of index (G:H) = p in G to the derived subgroup G ' are introduced as an innovative tool for identifying G uniquely by means of the family of kernels ùd(G) =(ker(T H,G ')) (G: H) = p. For all finite 3-groups G of coclass cc(G) = 1, the family ùd(G) is determined explicitly. The results are applied to the Galois groups G =Gal(F3 (∞)/ F) of the Hilbert 3-class towers of all real quadratic fields F = Q(√d) with fundamental discriminants d > 1, 3-class group Cl3(F) □ C3 × C3, and total 3-principalization in each of their four unramified cyclic cubic extensions E/F. A systematic statistical evaluation is given for the complete range 1 d 7, and a few exceptional cases are pointed out for 1 d 8.展开更多
Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response.Non-self intracellular proteins are processed into short peptides and...Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response.Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class I molecules assisted by several chaperone proteins to form trimeric complex.MHC class I complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells.The cells presenting non-self peptides are cleared by CD8 positive T cells.In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class I expression must be carefully regulated.Many of the cellular components involved in antigen processing and class I presentation are known and their various functions are now becoming clearer.Cellular & Molecular Immunology.2004;1(1):22-30.展开更多
基金Supported by Development funds from Section of Gastroenterology/Hepatology, Internal Medicine, University of Nebraska Medical Center
文摘Alcoholic patients have a high incidence of hepatitis C virus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability 'of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.
基金Supported by The Spanish Ministry of Education and Science,No.AGL2009-12438/GAN
文摘Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism causing transient infections. Despite all scientific efforts, there are still some gaps in the knowledge of the pathogenesis of this disease. Antigen presenting cells(APCs), as initiators of the immune response, are located in the first line of defense against microorganisms, and are responsible for antigen recognition, processing and presentation. Dendritic cells(DCs) are the main type of APC involved in antigen presentation and they are susceptible to PRRSV infection. Thus, PRRSV replication in DCs may trigger off different mechanisms to impair the onset of a host effective immune response against the virus. On the one side, PRRSV may impair the basic functions of DCs by regulating the expression of major histocompatibility complex class Ⅱ and CD80/86. Other strategy followed by the virus is the induction of cell death of APCs by apoptosis, necrosis or both of them. The impairment and/or cell death ofAPCs could lead to a failure in the onset of an efficient immune response, as long as cells could not properly activate T cells. Future aspects to take into account are also discussed in this review.
文摘Recent examples of periodic bifurcations in descendant trees of finite p-groups with ?are used to show that the possible p-class tower groups G of certain multiquadratic fields K with p- class group of type (2,2,2) , resp. (3,3), form periodic sequences in the descendant tree of the elementary Abelian root , resp. . The particular vertex of the periodic sequence which occurs as the p-class tower group G of an assigned field K is determined uniquely by the p-class number of a quadratic, resp. cubic, auxiliary field k, associated unambiguously to K. Consequently, the hard problem of identifying the p-class tower group G is reduced to an easy computation of low degree arithmetical invariants.
文摘Let F be a number field and p be a prime. In the successive approximation theorem, we prove that, for each integer n ≥ 1, finitely many candidates for the Galois group of the nth stage of the p-class tower over F are determined by abelian type invariants of p-class groups C1pE of unramified extensions E/F with degree [E : F] = pn-1. Illustrated by the most extensive numerical results available currently, the transfer kernels (TE, F) of the p-class extensions TE, F : C1pF → C1pE from F to unramified cyclic degree-p extensions E/F are shown to be capable of narrowing down the number of contestants significantly. By determining the isomorphism type of the maximal subgroups S G of all 3-groups G with coclass cc(G) = 1, and establishing a general theorem on the connection between the p-class towers of a number field F and of an unramified abelian p-extension E/F, we are able to provide a theoretical proof of the realization of certain 3-groups S with maximal class by 3-tower groups of dihedral fields E with degree 6, which could not be realized up to now.
文摘Let p be a prime. For any finite p-group G, the deep transfers T H,G ' : H / H ' → G ' / G " from the maximal subgroups H of index (G:H) = p in G to the derived subgroup G ' are introduced as an innovative tool for identifying G uniquely by means of the family of kernels ùd(G) =(ker(T H,G ')) (G: H) = p. For all finite 3-groups G of coclass cc(G) = 1, the family ùd(G) is determined explicitly. The results are applied to the Galois groups G =Gal(F3 (∞)/ F) of the Hilbert 3-class towers of all real quadratic fields F = Q(√d) with fundamental discriminants d > 1, 3-class group Cl3(F) □ C3 × C3, and total 3-principalization in each of their four unramified cyclic cubic extensions E/F. A systematic statistical evaluation is given for the complete range 1 d 7, and a few exceptional cases are pointed out for 1 d 8.
文摘Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response.Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class I molecules assisted by several chaperone proteins to form trimeric complex.MHC class I complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells.The cells presenting non-self peptides are cleared by CD8 positive T cells.In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class I expression must be carefully regulated.Many of the cellular components involved in antigen processing and class I presentation are known and their various functions are now becoming clearer.Cellular & Molecular Immunology.2004;1(1):22-30.