Search results for "Immune system"
showing 10 items of 2885 documents
Eliminating Factor H-Binding Activity of Borrelia burgdorferi CspZ Combined with Virus-Like Particle Conjugation Enhances Its Efficacy as a Lyme Dise…
2018
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the U.S and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H. To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds factor H to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because factor H-binding cloaks potentially pro…
The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications
2021
Tumor infiltrating lymphocytes (TIL) therapy was shown to provide durable objective response in patients with metastatic melanoma. As a fundamental first step to bring TIL therapy to clinical use, identification of patients whose tumors yield optimal numbers of reactive TIL is indispensable. We have previously shown that expansion of tumor reactive TIL from primary bladder tumors and lymph node metastases is feasible. Here, we performed TIL harvesting from additional surgical specimens (additional 31 primary tumors and 10 lymph nodes) to generate a heterogenous cohort of 53 patients with bladder cancer (BC) to evaluate the tumor characteristics that lead to tumor-reactive TIL expansion. Amo…
Prognostic Value of Complement Properdin in Cancer
2021
© 2021 Mangogna, Varghese, Agostinis, Alrokayan, Khan, Stover, Belmonte, Martorana, Ricci, Bulla and Kishore. The complement system is readily triggered by the presence of damage-associated molecular patterns on the surface of tumour cells. The complement alternative pathway provides rapid amplification of the molecular stress signal, leading to complement cascade actvation to deal with pathogens or malignant cells. Properdin is the only known positive regulator of the alternative pathway. In addition, properdin promotes the phagocytic uptake of apoptotic T cells by macrophages and dendritic cells without activating the complement system, thus, establishing its ability to recognize “altered…
TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in monocytes and dendritic …
2009
TLRs represent the first line of defense against invading pathogens in the innate immune system. Certain cytokines are important mediators and essentially necessary to assure an appropriately regulated immune response. Recent data gave initial evidence that IL-1beta is one of the most relevant members of these regulating cytokines. We investigated the induction of IL-1beta production in monocytes and pDCs stimulated with ligands for TLR7 and TLR8 and with antiphospholipid antibodies (aPL). Using human monocytes and pDCs for stimulation with specific TLR7 and TLR8 ligands such as resiquimod (R848) and single stranded RNA (RNA42) as well as with a human monoclonal aPL HL5B resulted in a speci…
Generation and characterization of three monoclonal IgM antiphospholipid antibodies recognizing different phospholipid antigens.
2005
Antiphospholipid antibodies (APLs) might be involved in the pathogenesis of the antiphospholipid syndrome (APS). This study analyzes the structural characteristics of monoclonal APLs derived from patients with this disease. Patient-derived B cells were immortalized using Epstein-Barr virus transformation and subsequent fusion to the myeloma cell line CB-F7. APL-producing hybridomas were cloned to obtain cell lines producing monoclonal APL. DNA encoding the variable region of heavy and light chains of the antibodies was sequenced and analyzed regarding their usage within the V-gene family and the existence of somatic hypermutation. Binding patterns of APL to various phospholipids and beta-2-…
Analysis of the immune response induced by a single xenoantigen in vivo
2004
Transgenic mice expressing human major histocompatibility complex (MHC) class II molecules would provide a valuable model system for studying murine anti-human MHC immune response. We have previously shown that skin from HLA-DR1 transgenic mice was rejected by control littermates and spleen cells from rejecting mice were able to proliferate to donor cells. The aim of this paper is to analyze the mechanism of recognition of this xenoantigen and the possible involvement of antibody response in anti-HLA-DR1 immune response. Control littermates were immunized with spleen cells from HLA-DR1 transgenic (TG) mice; at indicated times, xenoantigen-specific proliferation and IFNgamma production was a…
Angiotensin II-induced vascular dysfunction depends on interferon-γ-driven immune cell recruitment and mutual activation of monocytes and NK-cells.
2013
Objective— Immune cells contribute to angiotensin II (ATII)–induced vascular dysfunction and inflammation. Interferon-γ (IFN-γ), an inflammatory cytokine exclusively produced by immune cells, seems to be involved in ATII-driven cardiovascular injury, but the actions and cellular source of IFN-γ remain incompletely understood. Approach and Results— IFN-γ −/− and Tbx21 −/− mice were partially protected from ATII-induced (1 mg/kg per day of ATII, infused subcutaneously by miniosmotic pumps) vascular endothelial and smooth muscle dysfunction, whereas mice overexpressing IFN-γ showed constitutive vascular dysfunction. Absence of T-box expressed in T cells (T-bet), the IFN-γ transcription factor…
TLR4 polymorphisms and ageing: implications for the pathophysiology of age-related diseases.
2009
Innate immunity provides a first line of host defense against infection by recognizing and killing microbes while simultaneously activating an instructive immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition and function mainly by detection of pathogen-associated molecular patterns that do not exist in the host. Recognition of their ligands leads to a series of signaling events resulting in acute host responses, involved in killing pathogens. Discussion We describe the involvement of TLR4 polymorphisms in ageing, and in particular in age-related diseases, suggesting the crucial role of molecules of innate immunity in pathophysiology of these dis…
Giant cell arteritis-related aortitis with positive or negative temporal artery biopsy: a French multicentre study.
2019
Objective: To compare the clinical presentation and outcome of giant cell arteritis (GCA)-related aortitis according to the results of temporal artery biopsy (TAB).Method: Patients with GCA-related...
Hepatocellular carcinoma in patients with autoimmune hepatitis.
2009
To evaluate and confirm the low incidence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH). At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published, suggesting that HCC due to AIH is rare.In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH.Eighty-nine patients (32%) were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed H…