Specific Host Restance: The Effector Mechanisms
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Cytolytic T lymphocytes (CTLs) are lymphocytes programmed to destroy target cells in an antigen-specific fashion. They are T cells identified by the CD8 protein on their surface and are therefore referred to as CD8+. They have been extensively studied because they are the cells primarily responsible for graft rejection (chapter 11). CTLs are also capable of recognizing virus and other parasite-produced proteins present on the surfaces of host cells in association with Class 1 MHC molecules (Figure 9.11). Despite the damage to the host which may result from the destruction of infected host cells, the recognition and destruction of viruses and other intracellular parasites by the destruction of infected host cells is the only way the host can rid itself of such infections.
Basic Knowledge of Host Defenses Against Infection
M. T. Labro in Host Defense and Infection, 1994
Effector T Cells Cytotoxic T lymphocytes recognize antigens associated with class I MHC products on the presenting cell (which results in generation of “primed” cytotoxic T cells) and on target cells (e.g., virus-infected or tumor cells), which they can lyse by the mean of cytotoxic molecules (perforin, TNF-like molecules, etc.). Cytotoxic T cells possess the CD8 marker.Delayed-typed hypersensitivity T cells are responsible for DTH reactions. They recognize antigens associated with class IIMHC products and possess the CD4 marker. Their proinflammatory activity is supported by the production of IL-2.
The Major Histocompatibility Complex
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Antigen presentation is essential for T cell antigen recognition. This is because T cell receptors (TCRs) do not recognize intact antigens (as do antibodies); TCRs interact only with antigen fragments, i.e., peptides. Furthermore, these peptides are only recognized when they associate with self MHC molecules. Antigen presentation is the processing (degradation) of native antigen to yield peptides which complex with MHC expressed on the cell surface for recognition by the TCR. The CD4 and CD8 molecules determine the MHC class the T cell uses for recognition. CD4 is a receptor for MHC class II, and T cells which express CD4 recognize peptides associated with MHC class II. Similarly, CD8+ T cells recognize peptides associated with MHC class I molecules (see Chapter 6).
Adipose-Derived Mesenchymal Stem Cells Attenuate Immune Reactions Against Pig Decellularized Bronchi Engrafted into Rat Tracheal Defects
Published in Organogenesis, 2023
Makoto Hisanaga, Tomoshi Tsuchiya, Hironosuke Watanabe, Koichiro Shimoyama, Mayumi Iwatake, Yukinori Tanoue, Keizaburo Maruyama, Hiroshi Yukawa, Kazuhide Sato, Yoshimi Kato, Keitaro Matsumoto, Takuro Miyazaki, Ryoichiro Doi, Koichi Tomoshige, Takeshi Nagayasu
Infiltrating macrophages have either a proinflammatory (M1) or anti-inflammatory (M2) phenotype.35,36 Immunochemistry results for CD8 (a cytotoxic T lymphocyte marker), CD68 (a pan-macrophage marker), and CD163 (an M2 macrophage marker) in the tissue surrounding the implanted engineered trachea are shown in Figure 4a. We used CD8 expression as a marker for T-cells. The number of CD8+ lymphocytes was significantly lower in the Decellularized Xenograft+ADMSC group relative to the native and Decellularized Xenograft groups (Figure 4b; p = 0.049 and p = 0.0062, respectively). The number of CD68+ macrophages was similar in all groups. However, comparison with results in the Decellularized Xenograft group revealed that ADMSC administration significantly increased CD163+ cell infiltration into the tissues surrounding the grafts (Figure 4b; p = 0.0026). The number of CD163+ cells in the Decellularized Xenograft+ADMSC group was thus significantly higher than that in the native group (Figure 4b; p = 0.0016).
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
Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma
Published in Expert Review of Anticancer Therapy, 2022
CD4+ and CD8 + T-cells are predominantly responsible for the process of immunosurveillance of cancer cells. A hallmark of tumorigenesis is immunoediting, a process of tumor cell selection by the immune system for clones capable of escaping immune pressure. Immune escape includes genetic and epigenetic changes that result in (1) alterations in tumor antigen expression, (2) production of factors that negatively regulate T-cells, (3) changes to the tumor microenvironment to upregulate immune cells such as regulatory T-cells and myeloid-derived suppressor cells and (4) downregulation of MHC molecules [45–47]. CD8+ and CD4+ lymphocytes require MHC class I and II, respectively, to recognize tumor antigens in the same fashion as they would foreign peptides by antigen presenting cells.
Related Knowledge Centers
- Cell Signaling
- Cluster of Differentiation
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- Major Histocompatibility Complex
- Mhc Class I
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- Glycoprotein
- Cluster of Differentiation
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- T-Cell Receptor
- Antigen