The Viruses
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Interferons are a family of proteins produced by host cells in response to a variety of stimuli including viral infection. The formation of double stranded viral RNA within the infected cell induces the formation of interferons. Interferons may induce an antiviral state within many cells in the body. The production of interferons is a basic defense mechanism of animals against viral infections. There are three distinct types of interferons (alpha, beta, and gamma). Alpha and beta interferons bind to specific cell receptors and cause cells to produce proteins that have antiviral properties. For example, 2–5A synthetase causes the activation of nucleases that mediate degradation of viral RNAs. Gamma interferon, which is produced by leukocytes, causes the activation of macrophages and the production of antiviral cytokines which amplify the antiviral immune response.
Vaginal Immunology
William J. Ledger, Steven S. Witkin in Vulvovaginal Infections, 2017
Macrophages possess multiple TLRs and nonspecifically recognize a variety of microbial pathogens. They also possess membrane-bound receptors for complement and immunoglobulins and opsonize and destroy microorganisms that contain these components on their surface. The association of TLRs with its appropriate ligand results in activation of macrophage genes that code for proinflammatory cytokines and chemokines. Their release leads to the recruitment of T lymphocytes and the induction of pathogen-specific immunity. Once within the macrophage, ingested microorganisms are degraded, and their components become available for induction of antigen-specific acquired immunity, similar to what occurs in dendritic cells. In the lymph nodes, T lymphocytes also become activated to release the cytokine, interleukin 2 (IL-2). IL-2 induces the replication of T and B lymphocytes, resulting in the formation of a large number of lymphocytes that can recognize and respond to a specific microbial invader. Interferon gamma is also released by the activated T cells and stimulates macrophages to become more efficient in engulfing and processing microorganisms. A repertoire of T and B lymphocytes is generated (memory cells) that will recognize the specific microorganism if it should ever reappear in the future and quickly activate a cell-mediated and/or antibody-mediated immune response to prevent its proliferation and ability to cause disease.
Toxoplasma gondii
Peter D. Walzer, Robert M. Genta in Parasitic Infections in the Compromised Host, 2020
The control of severe toxoplasma infection is ultimately dependent on the development of an adequate cell-mediated immune response to the pathogen. With the development of recombinant genetic engineering techniques to manufacture lymphokines that enhances cell-mediated immune function, immunotherapy alone or in conjunction with specific chemotherapy may be useful in reversing this relapsing illness in the severely immunocompromised host. Gamma-interferon has been shown to augment natural killer cell activity and to activate macrophages (see Section VI). Both of these effector cells have been implicated as having a prominent role in host resistance to toxoplasma infection. In studies of the effect of interferon administration on host resistance to acute toxoplasma infection, McCabe et al. (389) demonstrated that interferon fully protected or significantly prolonged the life of mice infected with T. gondii. These interferon-treated mice also had enhanced antibody synthesis and earlier activation of macrophages. Further studies are needed to determine whether interferon is a useful adjunct in combination with chemotherapeutic agents in the treatment of significant toxoplasma infection.
Promising predictors of checkpoint inhibitor response in NSCLC
Published in Expert Review of Anticancer Therapy, 2020
Friedlaender Alex, Addeo Alfredo
Gene expression profiles (GEPs) can allow for a more complex and accurate analysis of the tumor microenvironment in a more precise manner than a single protein, such as PD-L1. Interferon gamma is key cytokine in the T-cell mediated immune response. However, it is also responsible for negative feedback, downregulating the inflammatory response by enabling upregulation of PD-L1 in tumor, immune and stromal cells. Cancer cells take advantage of this balance to survive. A T-cell inflamed GEP comprising 10 genes directly associated with IFN-gamma signaling was able to predict response to PD-1 blockade in melanoma [55]. In a recent GEP in NSCLC, 395 genes involved in the function of lymphocyte regulation, cytokine signaling, immune checkpoints, and tumor characterization were used to predict response to ICPIs. A composite predictive biomarker with peripheral T cell signatures (HLA-DOA, GPR18, STAT1) and the ‘’M1 signature” (CBLB, CCR7, CD27, CD48, FOXO1, FYB, HLA-B, HLA-G, IFIH1, IKZF4, LAMP3, NFKBIA, and SAMHD1), showed high sensitivity and specificity in predicting response and was able to identify patients with a median OS of 42 months, compared to 14 months in patients without these profiles [56]. These early results are promising but require prospective validation.
Aluminum hydroxide nebulization-induced redox imbalance and acute lung inflammation in mice
Published in Experimental Lung Research, 2020
Erika Tiemi Kozima, Ana Beatriz Farias de Souza, Thalles de Freitas Castro, Natália Alves de Matos, Nicole Elizabeth Philips, Guilherme de Paula Costa, André Talvani, Sílvia Dantas Cangussú, Frank Silva Bezerra
Inflammatory responses consist of coordinated activation of signaling pathways, expression and production of inflammatory mediators, and activation and trapping of inflammatory cells to the site of inflammation.43 In this study, we performed immunoenzymatic assays to verify the involvement of chemokines (CCL2) and cytokines (TNF and IFN) in the pulmonary inflammatory process. In our study, IFN-γ concentration was higher in the group exposed to aluminum hydroxide. Interferon gamma is recognized as the major cytokine involved in the activation of macrophages and is produced by lymphocytes, particularly natural killer (NK) cells, and by subsets of T cells.44–46 Davis et al. observed an increase in IFN production by different lymphocyte phenotypes in mice with silicosis.47 In our study, the increase in IFN may be related to a greater presence of lymphocytes in the pulmonary parenchyma and suggest that this cytokine is involved in the inflammatory response triggered by exposure to aluminum.
IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells
Published in OncoImmunology, 2021
Can Fang, Tao Weng, Shaojie Hu, Zhiwei Yuan, Hui Xiong, Bing Huang, Yixin Cai, Lequn Li, Xiangning Fu
Interferon-gamma (IFN-γ) is a key moderator of cellular immunity and secreted by activated T lymphocytes, γδT cells, and natural killer cells. IFN-γ has attracted much attention because of its significant role in promoting antitumor immune responses. Numerous recent studies have indicated that active IFN-γ signaling is a common feature in tumors that respond to immune checkpoint blockades through antibodies targeting CTLA-4 and PD-1/PD-L1.1,2 Loss of IFN-γ pathway genes in tumor cells reduces the chance of response to the immunotherapy with anti-CTLA-4.3 New studies using state-of-the-art technology have shown that while IFN-γ secretion requires local antigen recognition, IFN-γ diffuses extensively to alter the tumor microenvironment in a distant area. These findings imply the feasibility of activated tumor-infiltrating CD8+ T cells, through IFN-γ to modulate the behavior of remote tumor cells.4,5 Substantial evidence shows that besides its role in activating cellular immunity and enhancing antitumor immune response, active IFN-γ signaling triggers apoptosis and cell cycle arrest in human cancer cells, and acts as a direct anticancer agent.6,7 The mechanism underlying the IFN-γ-mediated anticancer effects remains unclear.
Related Knowledge Centers
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