scholarly journals A máj és az immunrendszer

2015 ◽  
Vol 156 (30) ◽  
pp. 1203-1213 ◽  
Author(s):  
Lajos Jakab
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Growth Factor ◽  
B Lymphocytes ◽  
Acute Phase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Acute Phase Reaction ◽  
Specific Immune Response ◽  
Phase Reaction

The liver is known to be the metabolic centre of the organism and is under the control of the central nervous system. It has a peculiar tissue structure and its anatomic localisation defines it as part of the immune system having an individual role in the defence of the organism. The determinant of its particular tissue build-up is the sinusoid system. In addition to hepatocytes, one cell row “endothelium”, stellate cells close to the external surface, Kupffer cells tightly to its inner surface, as well as dendritic cells and other cell types (T and B lymphocytes, natural killer and natural killer T-cells, mast cells, granulocytes) are present. The multitudes and variety of cells make it possible to carry out the tasks according to the assignment of the organism. The liver is a member of the immune system having immune cells largely in an activated state. Its principal tasks are the assurance of the peripheral immune tolerance of the organism with the help of the haemopoetic cells and transforming growth factor-β. The liver takes part in the determination of the manner of the non-specific immune response of the organism. In addition to acute phase reaction of the organism, the liver has a role in the adaptive/specific immune response. These functions include retardation of the T and B lymphocytes and the defence against harmful pathogens. With the collaboration of transforming growth factor-β, immunoglobulins and their subclasses are inhibited just as the response of the T lymphocytes. The only exception is the undisturbed immunoglobulin A production. Particularly important is the intensive participation of the liver in the acute phase reaction of the organism, which is organised and guided by the coordinated functions of the cortico-hypothalamo-hypophysis-adrenal axis. Beside cellular elements, hormones, adhesion molecules, chemokines and cytokines are also involved in the cooperation with the organs. Acute phase reactants play a central role in these processes. Until recently the α2-macroglobulin was not considered as an acute reactant of the organism, but it is now functionally included in the acute phase reaction presumably due to its close connection with the transforming growth factor-β. Transforming growth factor-β has extraordinarily important roles in all phases of inflammation and in the specific immune response. The peripheral immune tolerance of the organism involves tightly coupled regulation of proliferation, differentiation and survival of lymphocytes. Orv. Hetil., 2015, 156(30), 1203–1213.

scholarly journals Targeting Transforming Growth Factor β to Enhance Cancer Immunotherapy

2006 ◽  
Vol 13 (4) ◽  
pp. 141-143 ◽  
Author(s):  
T. Hahn ◽  
Emmanuel Akporiaye
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Human Tumours

Human tumours have evolved intricate mechanisms to evade the immune system, either by avoiding recognition or by inhibiting and eliminating immune cells. [...]

scholarly journals Transforming Growth Factor β Subverts the Immune System into Directly Promoting Tumor Growth through Interleukin-17

2008 ◽  
Vol 68 (10) ◽  
pp. 3915-3923 ◽  
Author(s):  
Jeong-Seok Nam ◽  
Masaki Terabe ◽  
Mi-Jin Kang ◽  
Helen Chae ◽  
Nga Voong ◽  
...  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Tumor Growth ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 17

A GMCSF & IL15 Fusokine Leads to Paradoxical Immunosuppression In Vivo Via Asymmetrical JAK/STAT Signalling through the IL15 Receptor Complex.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3187-3187
Author(s):  
Moutih Rafei ◽  
Jian Hui Wu ◽  
Borhane Annabi ◽  
Laurence Lejeune ◽  
Moira Francois ◽  
...  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Adaptive Immune System ◽  
Transforming Growth Factor Β ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Mouse Splenocytes

Abstract Immune stimulatory cytokines can be exploited to treat human ailments including cancer. Amongst cytokines identified for such use, granulocyte-macrophage colony stimulating factor (GMCSF) has been under much scrutiny since it acts directly on the adaptive immune system by enhancing antigen presentation as well as costimulation. Furthermore, interleukin (IL)15 possesses overlapping activities with IL2 such as the activation of T-cells and the stimulation of natural killing as well as additive stimulatory effects on the immune system distinct from IL2. These features make IL15 an attractive companion to GMCSF as part of an immunotherapeutic fusokine. Therefore, we hypothesized that a GMCSF and IL15 fusion protein (GIFT15) would possess greater immune stimulatory properties than their combined use. Unexpectedly, tumor cells engineered to secrete GIFT15 protein led to enhanced tumor growth and suppression of natural killer (NK) and NKT-cell recruitment in vivo, suggesting an unheralded immune suppressive effect. We found that GIFT15 has pleiotropic effects on an array of immune competent cells. More specifically, peritoneal macrophages treatment with GIFT15 secrete de novo the tissue inhibitor of metalloproteinase-2 (TIMP-2); activated matrix metalloproteinase-2 (MMP-2); transforming growth factor-β (TGF-β) as well as vascular endothelial growth factor (VEGF). In terms of ligand-receptor interactions, we show by BIAcore analysis that the GIFT15 fusokine has increased affinity for the αchain component of the trimeric IL15R, which contributes to aberrant signalling through the β chain manifested by the hyperphosphorylation of STAT3 both in macrophages and splenocytes. In addition, GIFT15 and IL15R virtual interaction studies suggests that the GMCSF domain component of the GIFT15 fusokine may hinder the interaction of the IL15 domain component with the IL15Rγ chain, and thus leading to a downregulation of the JAK3/STAT5 pathway. We also show that GIFT15 leads to suppression of common γ chain-mediated STAT5 phosphorylation and blockade of the IL15-dependent IFN-γ response in mouse splenocytes We tested the utlity of GIFT15 as an immunosuppressor directly in vivo and demonstrated that it allowed engraftment of allogeneic B16F0 and human xenograft U87MG glioma cells in immunocompetent mice in a CD4-dependent maner. Thus, GIFT15 defines a new class of fusokine which mediates pro-angiogenic and potent immunosuppressive effects via aberrant signalling by the IL15R in lymphomyeloid cells. We propose that GIFT15 may serve as a novel pharmaceutical for tolerance induction of somatic allo or xenografts in mammals without requirement of toxic conditioning regimens.

Saccharomyces cerevisiae var. boulardii CNCM I-1079 and Lactobacillus acidophilus BT1386 influence innate immune response and serum levels of acute-phase proteins during weaning in Holstein calves

2018 ◽  
Vol 98 (3) ◽  
pp. 576-588 ◽  
Author(s):  
Bridget E. Fomenky ◽  
Johanne Chiquette ◽  
Martin Lessard ◽  
Nathalie Bissonnette ◽  
Guylaine Talbot ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Immune Response ◽  
Innate Immune Response ◽  
Acute Phase ◽  
Oxidative Burst ◽  
Lactobacillus Acidophilus ◽  
Innate Immune ◽  
Acute Phase Reaction ◽  
Phase Reaction ◽  
Holstein Calves

The aims of this study were to investigate the effect of Saccharomyces cerevisiae var. boulardii CNCM I-1079 (SCB) or Lactobacillus acidophilus BT1386 (LA) on (1) innate immune response, (2) markers of acute-phase reaction, and (3) immune gene expression of rumen and ileum tissues of Holstein calves. Forty eight calves (∼5 d old) were randomly allocated to four treatments as follows: (1) control (CTRL) fed milk replacer followed by starter feed, (2) CTRL supplemented with SCB in milk and feed, (3) CTRL supplemented with LA in milk and feed, and (4) CTRL supplemented with antibiotics (ATB; chlortetracycline and neomycin in milk, and chlortetracycline in feed). Tumor necrosis factor α (TNF-α) decreased (P < 0.05) on day 66 (post-weaning) for the ATB-treated calves. There were no treatment effects on production of interferon γ (IFN-γ) and interleukin 6 (IL-6) proteins and on expression of TLR4, TLR6, TLR9, TLR10, CLDN3, MUC1, and MUC20 genes. Calves fed SCB or LA had a greater (P < 0.05) oxidative burst at weaning (day 53) compared with CTRL. Oxidative burst was also greater (P < 0.05) after weaning (day 59 and day 87) for SCB-fed calves. Calves fed SCB and ATB had higher (P < 0.05) phagocytosis activity during weaning (day 47) compared with CTRL. The concentration of serum amyloid A2 (SAA2) increased (P < 0.05) in SCB- and LA-fed calves (day 53), whereas the concentration of C-reactive protein (CRP) increased (P < 0.05) in SCB-fed calves during weaning as compared with CTRL. Our results suggest that SCB could improve innate immune response (oxidative burst and phagocytosis) and markers of acute-phase reaction (CRP and SAA2), especially during critical periods like weaning.

Intratubular epithelial-mesenchymal transition and tubular atrophy after kidney injury in mice

2020 ◽  
Vol 319 (4) ◽  
pp. F579-F591
Author(s):  
Noriyuki Yamashita ◽  
Tetsuro Kusaba ◽  
Tomohiro Nakata ◽  
Aya Tomita ◽  
Tomoharu Ida ◽  
...  
Keyword(s):  
Growth Factor ◽  
Acute Phase ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Chronic Phase ◽  
Transforming Growth Factor Β ◽  
Tubular Atrophy ◽  
Mesenchymal Transition

Tubular atrophy is a common pathological feature of kidney fibrosis. Although fibroblasts play a predominant role in tissue fibrosis, the role of repairing tubular epithelia in tubular atrophy is unclear. We demonstrated the essential role of focal adhesion kinase (FAK)-mediated intratubular epithelial-mesenchymal transition (EMT) in the pathogenesis of tubular atrophy after severe ischemia-reperfusion injury (IRI). Actively proliferating tubular epithelia undergoing intratubular EMT were noted in the acute phase of severe IRI, resulting in tubular atrophy in the chronic phase, reflecting failed tubular repair. Furthermore, FAK was phosphorylated in the tubular epithelia in the acute phase of severe IRI, and its inhibition ameliorated both tubular atrophy and interstitial fibrosis in the chronic phase after injury. In vivo clonal analysis of single-labeled proximal tubular epithelial cells after IRI using proximal tubule reporter mice revealed substantial clonal expansion after IRI, reflecting active epithelial proliferation during repair. The majority of these proliferating epithelia were located in atrophic and nonfunctional tubules, and FAK inhibition was sufficient to prevent tubular atrophy. In vitro, transforming growth factor-β induced FAK phosphorylation and an EMT phenotype, which was also prevented by FAK inhibition. In an in vitro tubular epithelia gel contraction assay, transforming growth factor-β treatment accelerated gel contraction, which was suppressed by FAK inhibition. In conclusion, injury-induced intratubular EMT is closely related to tubular atrophy in a FAK-dependent manner.

scholarly journals Diversion of the Immune Response to Neisseria gonorrhoeae from Th17 to Th1/Th2 by Treatment with Anti-Transforming Growth Factor β Antibody Generates Immunological Memory and Protective Immunity

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Yingru Liu ◽  
Michael W. Russell
Keyword(s):  
Immune Response ◽  
Growth Factor ◽  
Neisseria Gonorrhoeae ◽  
Primary Infection ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Content Type ◽  
Th2 Responses ◽  
Th1 And Th2 Responses ◽  
Th1 And Th2

ABSTRACTThe immune response toNeisseria gonorrhoeaeis poorly understood, but its extensive antigenic variability and resistance to complement are thought to allow it to evade destruction by the host’s immune defenses. We propose thatN. gonorrhoeaealso avoids inducing protective immune responses in the first place. We previously found thatN. gonorrhoeaeinduces interleukin-17 (IL-17)-dependent innate responses in mice and suppresses Th1/Th2-dependent adaptive responses in murine cellsin vitrothrough the induction of transforming growth factor β (TGF-β). In this study using a murine model of vaginal gonococcal infection, mice treated with anti-TGF-β antibody during primary infection showed accelerated clearance ofN. gonorrhoeae, with incipient development of Th1 and Th2 responses and diminished Th17 responses in genital tract tissue. Upon secondary reinfection, mice that had been treated with anti-TGF-β during primary infection showed anamnestic recall of both Th1 and Th2 responses, with the development of antigonococcal antibodies in sera and secretions, and enhanced resistance to reinfection. In mouse knockout strains defective in Th1 or Th2 responses, accelerated clearance of primary infection due to anti-TGF-β treatment was dependent on Th1 activity but not Th2 activity, whereas resistance to secondary infection resulting from anti-TGF-β treatment during primary infection was due to both Th1- and Th2-dependent memory responses. We propose thatN. gonorrhoeaeproactively elicits Th17-driven innate responses that it can resist and concomitantly suppresses Th1/Th2-driven specific adaptive immunity that would protect the host. Blockade of TGF-β reverses this pattern of host immune responsiveness and facilitates the emergence of protective antigonococcal immunity.IMPORTANCEPathogen-host interactions during infectious disease are conventionally thought of as two-way reactions, that of the host against the pathogen and vice versa, with the outcome dependent on which one ultimately prevails. We propose thatNeisseria gonorrhoeae, a pathogen that has become extremely well adapted to its exclusive human host, proactively directs the manner in which the host responds in ways that are beneficial to its own survival but detrimental to the host. Gonorrhea is a widely prevalent sexually transmitted infection, and naturally occurring gonococcal strains are becoming resistant to most available antibiotics, yet no effective vaccine has been developed. These new insights into the immune response toN. gonorrhoeaeshould lead to novel therapeutic strategies and facilitate new approaches to vaccine development.

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