Search results for " Immune system"
showing 10 items of 893 documents
CD8+CD45RA+CD27-CD28-T-cell subset in PBL of cervical cancer patients representing CD8+T-cells being able to recognize cervical cancer associated ant…
2003
Objective In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+CD45RA+CD28+T-cells undergo clonal expansion and differentiate into CD8+CD45RO+ memory T-cells. Upon re- encounter with the nominal antigen, CD45RO+ T-cells are able to convert to CD8+CD45RA+CD28-T-cells displaying potent immune effector functions, including TNF-alpha production. This T-cell subpopulation constitutes a minor population in healthy individuals. In the present study we are currently evaluating whether this particular T-cell subset in PBL represents CD8+T-cells which may be able to recognize cervical cancer associated antigens provided by HPV 16 E7. Material and methods Flow-cy…
Model for Generation of Large Numbers of Primary, Inflammatory Skin-Derived Neutrophils, and Macrophages
2012
Tissue macrophages and inflammatory neutrophils represent important cells of the innate immune system responsible for various important tasks, i.e., elimination of pathogens and/or granuloma formation. Isolation of large numbers of primary phagocytes is vital for research with these cells. Within this protocol, we present a strategy for isolation of large numbers of inflammatory neutrophils and macrophages from murine skin that allows for follow-up in vivo or in vitro studies.
Cellular Models and Assays to Study NLRP3 Inflammasome Biology
2020
The NLRP3 inflammasome is a multi-protein complex that initiates innate immunity responses when exposed to a wide range of stimuli, including pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Inflammasome activation leads to the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and to pyroptotic cell death. Over-activation of NLRP3 inflammasome has been associated with several chronic inflammatory diseases. A deep knowledge of NLRP3 inflammasome biology is required to better exploit its potential as therapeutic target and for the development of new selective drugs. To this purpose, in the past few years, several tools have…
Acute organ failure following the loss of anti-apoptotic cellular FLICE-inhibitory protein involves activation of innate immune receptors
2014
Apoptosis signaling is involved in both physiological tissue homeostasis and acute and chronic diseases. The role of regulatory apoptosis signaling molecules and their organ-specific functions are less defined. Therefore, we investigated the loss of the anti-apoptotic cellular FLICE-inhibitory protein (cFLIP) and the mechanisms of the resulting lethal organ failure in vivo using inducible knockout mice. These were generated by crossing floxed cFLIP mice to a tamoxifen inducible Rosa26-creERT2 mouse strain. Death following global loss of cFLIP resulted from liver failure, accumulation of M1-polarized macrophages and accompanying hepatic cell death and inflammation. Apoptosis was also promine…
SAT0378 Autophagy is Up-Regulated in the Salivary Glands of Primary Sjogren's Syndrome Patients and Correlates with the Focus Score and Disease Activ…
2015
Background Autophagy is now considered as a major regulator in trafficking events that activates innate and adaptive immunity and consistent evidence supports its role in autoimmunity (1). Primary Sjogren9s syndrome (pSS) is a systemic autoimmune disease characterized by infiltration of exocrine glands by T and B cells that, producing chemokines and cytokines, coordinate the chronic inflammatory process. No data on the role of autophagy in pSS are available in humans, although studies in mice demonstrated its involvement in the salivary and lacrimal gland homeostasis (2,3). Objectives We investigated the autophagy process in salivary gland tissue and in peripheral T lymphocytes from pSS pat…
Iron Metabolism in the Tumor Microenvironment-Implications for Anti-Cancer Immune Response
2021
New insights into the field of iron metabolism within the tumor microenvironment have been uncovered in recent years. Iron promotes the production of reactive oxygen species, which may either trigger ferroptosis cell death or contribute to malignant transformation. Once transformed, cancer cells divert tumor-infiltrating immune cells to satisfy their iron demand, thus affecting the tumor immunosurveillance. In this review, we highlight how the bioavailability of this metal shapes complex metabolic pathways within the tumor microenvironment and how this affects both tumor-associated macrophages and tumor-infiltrating lymphocytes functions. Furthermore, we discuss the potentials as well as th…
Zinc accelerates respiratory burst termination in human PMN
2021
The respiratory burst of phagocytes is essential for human survival. Innate immune defence against pathogens relies strongly on reactive oxygen species (ROS) production by the NADPH oxidase (NOX2). ROS kill pathogens while the translocation of electrons across the plasma membrane via NOX2 depolarizes the cell. Simultaneously, protons are released into the cytosol. Here, we compare freshly isolated human polymorphonuclear leukocytes (PMN) to the granulocytes-like cell line PLB 985. We are recording ROS production while inhibiting the charge compensating and pH regulating voltage-gated proton channel (HV1). The data suggests that human PMN and the PLB 985 generate ROS via a general mechanism,…
2013
Regulatory T cells (Treg) play a pivotal role in the immune system since they inhibit the T cell response. It is well known that cyclophosphamide applied at low dose is able to stimulate the immune response while high dose cyclophosphamide exerts inhibitory activity. Data obtained in mice indicate that cyclophosphamide provokes a reduction in the number of Treg and impairs their suppressive activity, resulting in immune stimulation. Here, we addressed the question of the sensitivity of human Treg to cyclophosphamide, comparing Treg with cytotoxic T cells (CTL) and T helper cells (Th). We show that Treg are more sensitive than CTL and Th to mafosfamide, which is an active derivative of cyclo…
Caspase-8 regulates TNF-alpha induced epithelial necroptosis and terminal ileitis
2011
Two groups identify the regulation of death-receptor-induced necroptosis as an epithelial intrinsic mechanism that is important for the maintenance of immune homeostasis and the prevention of intestinal inflammation in mice. Welz et al. describe an unexpected physiological function for FADD (Fas-associated protein with death domain), an adaptor protein required for death-receptor-induced apoptosis. Mice with intestinal epithelial specific knockout of FADD develop severe colon inflammation due to increased death of FADD-deficient colonic epithelial cells. Gunther et al. report a novel and unexpected function of caspase-8 in maintaining immune homeostasis in the gut. Caspase-8 expression by g…
Conversion of crustacean hemocyanin to catecholoxidase
2004
Crustacean hemocyanin as oxygen carrier and catecholoxidase as enzymes belong to the same protein family (type 3 copper proteins) sharing very similar active sites. Treatment with SDS of these hemocyanins results in an opening of the entrance to the active site for bulky phenolic compounds. This demonstrates, that almost all hemocyanin subunits possess the ability of catecholoxidase activity.