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Acquired Immunity
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
MHC class I molecules are antigens expressed on all nucleated cells. When a virus or intracellular bacterium invades a host cell, it stimulates the infected cell to synthesize proteins that are hydrolysed to form antigenic peptides that bind to MHC class I molecules. The MHC class I molecules interact with cytotoxic T lymphocytes (CD8 T cells) during antigen presentation, driving mainly cytotoxic reactions.
Immune function of epithelial cells
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Richard S. Blumberg, Wayne Lencer, Arthur Kaser, Jerrold R. Turner
Epithelial cells constitutively express complex (MHC) class I molecules and are capable of presenting endogenous antigens, in the context of MHC class I, for defense against infections and neoplasia. Endogenous antigens from epithelial cells can also be captured by local dendritic cells and cross-presented on MHC class I for priming of CD8+ T cells in draining lymph nodes. Epithelial cells also express MHC class II molecules, and do so preferentially in the small intestine. In response to pro-inflammatory stimuli, in particular, interferon-γ (IFN-γ), MHC II molecules are upregulated on epithelial cells. It has also been demonstrated that IFN-γ causes antigens to be sorted into MHC class II–positive late endosomes with presentation basolaterally in epithelial cell model systems. MHC class II is expressed constitutively by small intestinal epithelial cells and induced in colonic epithelium. Thus, epithelial cell expression of MHC class II can assist in the presentation of soluble antigens to CD4+ T cells and the presentation of intracellular antigens via MHC class I to CD8+ T cells during infection or neoplasia.
Inflammation and immunology
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Christopher Bellamy, Stephen J. Jenkins, Henry J. McSorley, David A. Dorward, Timothy J. Kendall
T cells recognize antigen presented to them on a cell surface and in association with molecules of the MHC. There are two families of MHC molecules: MHC I and MHC II. MHC class I is expressed on the surface of most tissue cells as a heterodimer of an α chain and a common β2-microglobulin. MHC class I is recognized by T lymphocytes of the CD8 class. In contrast, MHC class II is expressed only on a limited range of immune accessory cells and endothelium termed antigen-presenting cells that capture and present antigen from the tissue environment. MHC II exists as an αβ heterodimer and is recognized by CD4 subclass T lymphocytes. Protein antigen is presented to T lymphocytes by these molecules in the form of small, partially degraded peptides held in molecular grooves on the MHC molecules (Figure 4.15).
M2 macrophage-derived exosomes suppress tumor intrinsic immunogenicity to confer immunotherapy resistance
Published in OncoImmunology, 2023
Naisheng Zheng, Tingting Wang, Qin Luo, Yi Liu, Junyao Yang, Yunlan Zhou, Guohua Xie, Yanhui Ma, Xiangliang Yuan, Lisong Shen
Given the functional similarity of the protein profiles to both treatments, we sought to find the major common functional determinants associated with the immune response and ICB response in tumor cells with highly ApoE enrichment through M2-exosomal transfer or genetic overexpression. Of note, when running the profiling on the proteomics combined with available knowledge, the critical feature that indicates tumor immunogenicity was MHC-I downregulation by ApoE enrichment in tumor cells, which induces the insufficient antigen presentation to activate T cells comprises a large proportion of patients leading to ICB resistance. MHC class I (MHC-I), the key component in antigen presentation, presents intracellular peptide antigens to the cell surface for recognition by antigen-specific CD8+ T cells. MHC-I loss or downregulation in cancer cells is a major mechanism of resistance to T-cell-based immunotherapies.21,24,32
Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence
Published in Expert Review of Vaccines, 2022
Maryam Abbaspour, Vajihe Akbari
The main obstacle to an effective BC vaccine is immunosuppressive mechanisms of tumor microenvironment. Changes in MHC expression profile and abnormality in antigen processing machinery complex are usually responsible for cancer immunotherapy resistance and associated to poor prognosis in BC patients [146]. IL-10 and transforming growth factor-beta (TGF-β) are highly expressed in tumor microenvironment and can downregulate the expression of MHC class-I molecules [147]. MHC class I machinery mainly involves in presentation of cellular antigen to T cells. One mechanism through which cancer cells escape from natural immune responses or resist immunotherapies that particularly involve induction of tumor-specific CD8+ T cells response is decrease or loss of expression of MHC class I antigen presentation as it is not necessary for tumor cell survival [146]. de Kruijf et al., demonstrated that loss of classical MHC class I antigen expression in early BC patients is directly related with higher recurrence rates [148]. It was observed that interferons (INFs) type-I and type-II can upregulate the expression of MHC class I [149]. Combination of BC vaccines with INFs might overcome immunotherapy resistance due to loss of MHC class I [150]. A phase IIa trial is ongoing to evaluate the efficacy and safety of combination of DC vaccine, pembrolizumab (an immune checkpoint inhibitor) and interferon alpha-2b for the treatment of TNBC or HER2 positive BC patients with brain metastasis (NCT04348747).
Phenotype of Innate Immune Cells in Uveitis Associated with Axial Spondyloarthritis- and Juvenile Idiopathic Arthritis-associated Uveitis
Published in Ocular Immunology and Inflammation, 2021
Maren Kasper, Karoline Walscheid, Björn Laffer, Dirk Bauer, Martin Busch, Karin Loser, Thomas Vogl, Thomas Langmann, Gerd Ganser, Thomas Rath, Arnd Heiligenhaus
In the current study, 95% of the SpA cohort was HLA-B27 positive, and similar changes in monocytic subtypes as shown for HLA-B27-positive AAU patients without SpA were observed.26 This finding points toward an association between the presence of the HLA-B27 allele and an activated immune status in SpA/uveitis patients even during clinically quiescent uveitis. Influence of systemic treatment on the plasticity of monocytes as previously shown for Crohn´s disease and noninfectious uveitis27,66 could not be confirmed in our study. Data presented here showed an elevated expression level of MHC class I by monocytes in SpA patients, while no changes were observed in JIA patients. Similarly, elevated MHC-I-free chains on peripheral blood leukocytes, monocytes in particular, of HLA-B27+ SpA patients, but not of RA patients have been described.67