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《Immunobiology》2022,227(6):152279
Influenza A virus (IAV) is a contagious respiratory infection causing pathogen responsible for high morbidity and mortality rates across the planet. The human immune system contains a wide range of soluble activators, membrane-bound receptors, and regulators to eliminate IAVs. Despite these various immune mechanisms that neutralize IAVs or restrict their replication, IAVs have developed distinct strategies to evade host immunity and establish a successful infection. Given the higher and continuous rate of mutations in IAVs, decades of research have focused on understanding the host's immune mechanisms against IAVs, and the evasion strategies employed by the virus to overcome the host immune system. Future IAV pandemics or epidemics remain inevitable, and a greater understanding of the host-pathogen interaction involved is required to develop universal vaccines and treatments against IAV. Here, we review how the host immune system responds to IAV infection as well as the strategies employed by the IAV to evade host immune surveillance. Furthermore, this review also focuses on the treatments and vaccines that have been developed to counter IAV infection. 相似文献
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Laura Pasqualucci 《Immunological reviews》2019,288(1):240-261
B cell lymphomas comprise a heterogeneous group of genetically, biologically, and clinically distinct neoplasms that, in most cases, originate from the clonal expansion of B cells in the germinal center (GC). In recent years, the advent of novel genomics technologies has revolutionized our understanding of the molecular pathogenesis of lymphoid malignancies as a multistep process that requires the progressive accumulation of multiple genetic and epigenetic alterations. A common theme that emerged from these studies is the ability of lymphoma cells to co‐opt the same biological programs and signal transduction networks that operate during the normal GC reaction, and misuse them for their own survival advantage. This review summarizes recent progress in the understanding of the genetic and epigenetic mechanisms that drive the malignant transformation of GC B cells. These insights provide a conceptual framework for the identification of cellular pathways that may be explored for precision medicine approaches. 相似文献
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病毒和宿主共生过程中,病毒为了生存繁衍形成多种逃避宿主免疫反应的方式。其中病毒抗原变异逃逸抗体的中和和病毒干扰补体激活的关键环节来抑制宿主的抗病毒状态是病毒拮抗机体体液免疫反应的主要途径。此外,病毒还利用编码多种细胞因子的类似物干扰细胞因子的正常功能,造成有利于病毒生存复制的内环境,从而使得病毒能够持续感染机体。 相似文献
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Neutrophils are of key importance in periodontal health and disease. In their absence or when they are functionally defective, as occurs in certain congenital disorders, affected individuals develop severe forms of periodontitis in early age. These observations imply that the presence of immune-competent neutrophils is essential to homeostasis. However, the presence of supernumerary or hyper-responsive neutrophils, either because of systemic priming or innate immune training, leads to imbalanced host–microbe interactions in the periodontium that culminate in dysbiosis and inflammatory tissue breakdown. These disease-provoking imbalanced interactions are further exacerbated by periodontal pathogens capable of subverting neutrophil responses to their microbial community's benefit and the host's detriment. This review attempts a synthesis of these findings for an integrated view of the neutrophils' ambivalent role in periodontal disease and, moreover, discusses how some of these concepts underpin the development of novel therapeutic approaches to treat periodontal disease. 相似文献
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Most recently published complete bacterial genomes have revealed unexpectedly high numbers of long strict repeats. In this article we discuss the various functional and evolutionary roles of these repeats, focusing in particular on their role in terms of genome stability, gene transfer, and antigenic variation. 相似文献
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The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3 was investigated in single cell cytotoxicity assays, using K-562 target cells. The action of vitamin D3 sulfate (VD3S) in natural cytotoxicity assays as well as its effect on the antigen-specific adherence of hybridoma cells has also been studied. In the single cell cytotoxicity assay 1,25(OH2)D3 dose-dependently and significantly increased the binding of PBMC to target, the number of lysed target cells and NK activity, RU486, a compound known as a potent blocker of progesterone and glucocorticoid receptors, suppressed the effect of 1,25(OH2)D3 in all systems. VD3S dose-dependently decreased the natural cytotoxicity of PBMC and the binding of hybridoma cells to antigen immobilized on plastic surfaces. The results suggest that both 1,25(OH2)D3 and VD3S are potent 相似文献
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Dennis Vestergaard Pedersen Josefine Lorentzen Gregers Rom Andersen 《Immunological reviews》2023,313(1):46-59
Structures of alternative pathway proteins have offered a comprehensive structural basis for understanding the molecular mechanisms governing activation and regulation of the amplification pathway of the complement cascade. Although properdin (FP) is required in vivo to sustain a functional alternative pathway, structural studies have been lagging behind due to the extended structure and polydisperse nature of FP. We review recent progress with respect to structure determination of FP and its proconvertase/convertase complexes. These structures identify in detail regions in C3b, factor B and FP involved in their mutual interactions. Structures of FP oligomers obtained by integrative studies have shed light on how FP activity depends on its oligomerization state. The accumulated structural knowledge allows us to rationalize the effect of point mutations causing FP deficiency. The structural basis for FP inhibition by the tick CirpA proteins is reviewed and the potential of alphafold2 predictions for understanding the interaction of FP with other tick proteins and the NKp46 receptor on host immune cells is discussed. The accumulated structural knowledge forms a comprehensive basis for understanding molecular interactions involving FP, pathological conditions arising from low levels of FP, and the molecular strategies used by ticks to suppress the alternative pathway. 相似文献
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Leila Akkari Vasilena Gocheva Jemila C. Kester Karen E. Hunter Marsha L. Quick Lisa Sevenich Hao-Wei Wang Christoph Peters Laura H. Tang David S. Klimstra Thomas Reinheckel Johanna A. Joyce 《Genes & development》2014,28(19):2134-2150
During the process of tumor progression, cancer cells can produce the requisite growth- and invasion-promoting factors and can also rely on noncancerous cells in the tumor microenvironment as an alternative, cell-extrinsic source. However, whether the cellular source influences the function of such tumor-promoting factors remains an open question. Here, we examined the roles of the cathepsin Z (CtsZ) protease, which is provided by both cancer cells and macrophages in pancreatic neuroendocrine tumors in humans and mice. We found that tumor proliferation was exclusively regulated by cancer cell-intrinsic functions of CtsZ, whereas tumor invasion required contributions from both macrophages and cancer cells. Interestingly, several of the tumor-promoting functions of CtsZ were not dependent on its described catalytic activity but instead were mediated via the Arg–Gly–Asp (RGD) motif in the enzyme prodomain, which regulated interactions with integrins and the extracellular matrix. Together, these results underscore the complexity of interactions within the tumor microenvironment and indicate that cellular source can indeed impact molecular function. 相似文献
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Rheumatoid arthritis (RA) is a systemic autoimmune disease. We previously identified a circulating cell population, fibrocytes, which is activated early in disease. As RA is characterized by the formation of autoantibodies and autoreactive T cells, which often precede symptom onset, the objective of these studies was to characterize fibrocyte activation in the context of T cell activation. Multidimensional flow cytometry was used to characterize the activation status of peripheral blood (PB) fibrocytes and T cells derived from RA patients with different levels of disease activity. Compared to healthy controls, fibrocytes from RA patients exhibited increased activation, denoted as elevated levels of phosphorylation of STAT3 and NF-κB. RA patients had higher numbers of circulating activated Th17 cells and Tregs compared with healthy controls, Th17 cell numbers being higher in patients with moderate to high disease activity. Additionally, increased numbers of FOXP3+ RORγt+ double positive CD4+ T cells were observed in RA patients with more severe disease. Our data confirm that circulating fibrocytes are expanded in RA and that there is a direct correlation between the increase in number of activated fibrocytes and increased number of CD4+ T cells. Moreover, our data suggest that interactions between circulating fibrocytes and activated T cells may promote disease activity. Specifically, we provide in vitro evidence that mouse-derived CD4+ T cells produce GM-CSF which induces fibrocyte proliferation. In turn, activated fibrocytes produce IL-6, promoting Th17 polarization. 相似文献
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The progression of renal diseases: On the pathogenesis of renal interstitial fibrosis 总被引:2,自引:0,他引:2
G. A. Müller J. Markovic-Lipkovski H. P. Rodemann 《Journal of molecular medicine (Berlin, Germany)》1991,69(13):576-586
Summary Renal interstitial fibrosis (RIF) frequently occurs in inflammatory and non-inflammatory kidney diseases and is associated with a decline in renal excretory function. Fibroblasts which occupy the renal interstitium are involved mainly in the formation of RIF not only by the production of extracellular matrix, but also by regulatory processes. They respond to a variety of cytokines released by different cell types. To investigate mechanisms leading to RIF, immunohistochemical analysis and cell cultures of renal biopsies in various renal diseases have been performed. T lymphocytes are the major cells infiltrating the renal interstitium, and their number correlates with the impairment of renal function. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/-DP molecules, frequently associated with an aberrant expression of the intercellular adhesion molecule 1 (ICAM-1), was observed on proximal tubular epithelial cells, indicating that these cells may play a role in antigen presentation. The cell biological experiments revealed the presence of the three mitotic fibroblast types (MFI-MFIII) and the three postmitotic types (PMFIV-PMFVI) in the cell culture. The number of fibroblasts in primary and passage-1 culture was increased sevenfold in cultures derived from kidneys with RIF (FKIF cells) in comparison to normal kidneys (NKF cells). FKIF cells show hyperproliferative growth and synthesize an increased amount of total collagen, especially types III and V. These cells express a protein, named FIBROSIN, which seems to be specific for FKIF cells. Further extended cell biological analyses are currently being performed to investigate interactions of tubular cells, lymphocytes, macrophages, and fibroblasts in order to shed more light on the pathomechanisms involved in fibrogenesis leading to renal interstitial fibrosis.Abbreviations AG
antigen
- DMEM
Dulbecco's modified Eagle's medium
- ECM
extracellular matrix
- FACS
fluorescence activated cell sorter
- FGF
fibroblast growth factor
- FKIF
fibroblast derived from kidneys with interstitial fibrosis
- FSGS
focal segmental glomerulosclerosis
- GBM
glomerular basement membrane
- GM-CSF
granulocyte/macrophage-colony stimulating factor
- GN
glomerulonephritis
- HLA
human leukocyte antigen
- ICAM-1
intercellular adhesion molecule 1
- ICI
interstitial cellular infiltrate
- IgA N
immunoglobulin A nephropathy
- IL
interleukin
- INF-
interferon gamma
- LFA
leukocyte function antigen
- M-CSF
macrophage-colony stimulating factor
- MF
mitotic fibroblast
- MGN
membranous glomerulonephritis
- MesPrGN
mesangioproliferative glomerulonephritis
- MHC
major histocompatibility complex
- Min Ch
minimal changes
- Min Les
minor lesions
- MMC
mitomycin C
- MPGN
membranoproliferative glomerulonephritis
- NKF
normal kidney fibroblast
- NSF
normal skin fibroblast
- PDGF
platelet-derived growth factor
- PMF
postmitotic fibroblast
- PTEC
proximal tubular epithelial cells
- TGF
transforming growth factor
- TNF
tumor necrosis factor
- RIF
renal interstitial fibrosis
- RPGN
rapidly progressive glomerulonephritis
- TBM
tubular basement membrane
- TCR
T-cell receptor
Preprint of a lecture to be read at the 22nd Congress of the Gesellschaft für Nephrologie, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)Supported by the Deutsche Forschungsgemeinschaft DFG Mu 523/3-5, SFB 223, Project B5/Ro 527/2-2 and by the Alexander von Humboldt-Stiftung 相似文献
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Objective
The use of the telephone for providing healthcare is growing. The aim of this exploratory study was to describe tele-health lessons and strategies as discussed by specialists who provide information and recommendations on poison control hotlines.Methods
Three focus groups of 25 participants who work as specialists in poison information in poison control centers were conducted. Group discussions were analyzed using qualitative content analysis.Results
Themes that emerged from the data on strategies for telephone communication include: taking control of the call, developing a therapeutic relationship, tailoring communication to fit each caller, preventing information overload, confirming caller understanding, and hands-on training for the development of telephone communication skills.Conclusion
Specialists in poison information identified challenges specific to communicating with patients over the telephone and reported several types of strategies they used to manage them.Practice implications
Telephone communication training may be needed to assist health care providers in improving their communication skills. 相似文献18.
Involvement of small GTPases Rho and Rac in the invasion of rat ascites hepatoma cells 总被引:4,自引:0,他引:4
Fumio Imamura Mutsuko Mukai Masako Ayaki Koichi Takemura Takeshi Horai Kiyoko Shinkai Hiroyuki Nakamura Hitoshi Akedo 《Clinical & experimental metastasis》1999,17(2):141-148
Lysophosphatidic acid (LPA) triggers the invasion of a mesothelial cell monolayer by rat ascites hepatoma (MM1) cells. LPA also induces rapid morphological changes of MM1 cells, cell surface blebbing and pseudopodia formation. Pseudopodia formation is tightly correlated with cellular invasiveness. Clostridium Botulinum C3 exoenzyme and genistein abrogated the formation of blebs and pseudopodia together with the inhibition of invasion, indicating that GTPase Rho and certain tyrosine kinases are involved in both processes. MM1 cells expressing constitutively active Rho exhibited the invasion and the formation of blebs and pseudopodia in the absence of LPA. In contrast, MM1 cells expressing constitutively active Rac were not invasive in the absence of LPA, but were invasive in the presence of LPA. Their morphological response to LPA was almost the same as that of parental MM1 cells. Expression of dominant negative Rac suppressed the invasiveness to approximately 3% of that of parental MM1 cells, together with the inhibition of pseudopodia formation. Thus, Rho and Rac are cooperatively involved in both the invasion and the related morphological changes of MM1 cells. Rho activation is sufficient both for the induction of invasion and the morphological changes leading to the invasion, whereas Rac activation is necessary but not sufficient by itself. We propose that Rho activation is not mediated by Rac but the cooperation of both GTPases is essential to trigger the invasive behavior of MM1 cells. 相似文献
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A case of cystic embryonal sarcoma of the kidney (CESK) with a rapidly fatal outcome was recently reported.1 Here, we report another case of a 12-year-old boy with a localized but ill-defined submucosal lesion of CESK in the right renal pelvis. The tumor consisted principally of small mesenchymal cells with oval to spindle nuclei and scanty cytoplasm, infiltrating in dense arrangements. Two growth patterns were distinguished in the tumor cells: (i) a diffuse infiltrating pattern without an epithelial component; and (ii) a foliated pattern with an epithelial lining over the surface. Foci of the diffuse pattern predominated over those that were lobular, infiltrating superficial layers of renal sinuses and along pyramids, in both of which remarkable intravenous invasion was evident. Foci of the foliated pattern invaded deeper portions of a few sinuses and frequently penetrated into their veins, producing together with their epithelial lining a characteristic foliated structure. Lining epithelial cells around lobular foci often appeared hob-nailed or eosinophilic in the cytoplasm. Despite the remarkable intravenous encroachment, the patient has remained well without a recurrence for more than 26 years after a simple nephrectomy. The present case report expands our understanding of the biological nature of CESK. 相似文献
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Toxoplasma gondii is able to invade phagocytic cells of the monocyte-macrophage lineage and replicates within a parasitophorous vacuole. Since macrophages may activate specific T lymphocytes by presenting pathogen-derived antigens in association with molecules of the MHC, we investigated the in vitro expression of host cell molecules involved in antigen processing and presentation before and during infection of murine bone marrow-derived macrophages (BMM) with T. gondii. Fifty-one hours after addition of T. gondii tachyzoites at different parasite-to-host ratios, up-regulation of total MHC class II molecules by interferon-gamma (IFN-γ) was dose-dependently abrogated in up to 50% of macrophages compared with uninfected control cultures. Quantitative analyses by flow cytometry revealed that the IFN-γ-induced surface expression of class II antigens as well as the IFN-γ-induced up-regulation of class I molecules was significantly decreased in T. gondii-infected macrophage cultures compared with uninfected controls. However, the constitutive expression of MHC class I antigens was not altered after parasitic infection, and infected BMM remained clearly positive for these molecules. After infection of macrophages preactivated with IFN-γ for 48 h, T. gondii also actively down-regulated an already established expression of MHC class II molecules. Furthermore, kinetic analysis revealed that the reduction in intracellular and plasma membrane-bound class II molecules started ≈ 20 h after infection. While MHC class II antigens were most prominently reduced in parasite-positive host cells, culture supernatant from T. gondii-infected BMM cultures also significantly inhibited expression of these molecules in uninfected macrophages. However, down-regulation of MHC class II molecules was not mediated by an increased production of prostaglandin E2, IL-10, transforming growth factor-beta or nitric oxide by infected BMM compared with uninfected controls. Our data indicate that intracellular T. gondii interferes with the MHC class I and class II antigen presentation pathway of murine macrophages and this may be an important strategy for evasion from the host's immune response and for intracellular survival of the parasite. 相似文献