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The Human Immune System Seen from a Biomedical Engineering Viewpoint
Published in Robert B. Northrop, Endogenous and Exogenous Regulation and Control of Physiological Systems, 2020
Antigen presentation from cells carrying active MHC I molecules is made to leukocytes that carry the CD8 surface glycoprotein, as well as receptor proteins for the MHC I complex. CD8+ leukocytes are generally CTL. The TCR protein for MHC I molecules and adjacent CD8 protein molecules project through the surface of the CTL. Antigen presentation is only possible if the TCR protein has an affinity for the presented antigenic peptide nestled in the MHC I cleft, and the CD8 protein on the CTL binds to the MHC I side site. (See Figure 10.1 for an illustration of this process.) Once the CD8 and TCR proteins have bound to the antigen-presenting cell’s MHC I-peptide epitope complex, an internal, biochemical “message” is sent to the CTL, activating it to destroy the antigen-presenting cell. Destruction is necessary to prevent eclosión of reproduced virions or parasites from within the cell. The activated CTL either perforates the cell membrane of the infected cell with a special protein it secretes, or it sends chemical messengers to the infected cell that cause it to self-destruct by a process known as apoptosis (see Section 10.4).
Role of Nanoparticles in Cancer Immunotherapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
For a successful immune response, effective antigen presentation to the T cells is indispensable. NPs have shown the potential of delivering tumor antigen/epitopes to the classical APCs for better antigen presentations to elicit antitumor immune response during the vaccination.
Metal-Based Nanoparticles and the Immune System: Activation, Inflammation, and Potential Applications
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
Yueh-Hsia Luo, Louis W. Chang, Pinpin Lin
The innate immune system, also known as the non-specific immune system and the first line of defense, relies on the recognition of PAMPs through a limited number of germ line-encoded pattern recognition receptors, belonging to the family of toll-like receptors (TLRs) [25]. The Toll gene was originally discovered in Drosophila, responsible for dorsoventricular polarization during embryonic development and antifungal and antibacterial properties of the adult fly [26]. TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are present on the cell surface whereas TLR3, TLR7, TLR8, TLR9, TLR12, and TLR13 are localized into intracellular vesicles such as endosomes, lysosomes, and the endoplasmic reticulum (ER). TLR1/TLR2 sense bacterial tri-acylated lipopeptides. TLR2/TLR6 recognize di-acetylated lipopeptides and bacterial lipoteichoic acid or peptidoglycans and mycobacterial cell wall components. TLR3 binds to viral double stranded RNA while TLR4 responds to LPS, and TLR5 senses flagellin. TLR7 and TLR8 respond to the single stranded RNA from viruses, while TLR9 binds to DNA-containing unmethylated CpG motifs which are commonly found in bacterial DNA. TLR12 recognizes profilin, while TLR13 senses bacterial 23S ribosomal RNA (rRNA) [16]. The activation of TLR signaling can not only induce cytokine production but also increase macrophage phagocytosis and natural killer (NK) cells cytolytic activity. Most importantly, TLR signaling activation also can enhance antigen presentation via upregulating the expression of the major histocompatibility complex (MHC) and costimulatory molecules (CD80 and CD86) on dendritic cells leading to adaptive immunity activations. Thus, TLR agonists were believed to be powerful vaccine adjuvant, allergy, infection, and antitumor therapeutics in preclinical studies [24]. The TLR antagonists also have therapeutic value in clinical trials to treat septic shock and autoimmune disorders [27]. For example, TLR agonists or nanoparticles that enhance TLR signaling pathways would be powerful adjuvants [28, 29]. In contrast, TLR antagonists or inhibitors that reduced the inflammatory response would have beneficial therapeutic effects in autoimmune diseases and sepsis [30]. These potential applications may open up innovative directions for the design of nanoparticle conjugates to meet different requirements.
Genetic variants affecting chemical mediated skin immunotoxicity
Published in Journal of Toxicology and Environmental Health, Part B, 2022
Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme
The epidermis is mainly composed of keratinocytes (>90%) but also contains melanocytes and Langerhans cells (LC) (Abdo, Sopko, and Milner 2020), which are antigen-presenting cells (APCs) and take part in the skin immune system. Besides the essential role played by keratinocytes in maintaining the mechanical (Agache and Varchon 2017) and barrier functions of the epidermis, these cells also present sensor receptors able to trigger inflammatory responses, such as toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (Baker et al. 2003; Burian and Yazdi 2018). Upon binding to metabolites of stressed cells or exogenous substances (Lai and Gallo 2008; Patel 2018), these receptors engage in signal transduction pathways that activate several proinflammatory genes (Tabas and Glass 2013). Consequently, keratinocytes express proinflammatory cytokines – small hormone-like peptides involved in autocrine, paracrine, and endocrine signaling to act as immunomodulating agents and activate other cells, inducing an immune response (Zhang and An 2007). Proinflammatory cytokines produced by activated keratinocytes, such as tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1), induce the expression of the intercellular adhesion molecule-1 (ICAM-1), facilitating blood cell endothelial infiltration. The interferon – γ (IFN-γ) released by T cells might mediate the upregulation of MHC class II (MHC-II) on keratinocytes surface and enable them to promote antigen presentation to CD4+ T cells, as professional APCs (Black et al. 2007; Fan et al. 2003; Kim et al. 2009). In the context of tissue inflammation, keratinocytes directly activate autoreactive CD4+ T cells and participate in autoimmune skin diseases, such as psoriasis (Albanesi et al. 2005; Fan et al. 2003). Keratinocytes also present antigens to CD8+ T effector/memory cells (via MHC class I) in an antigen-specific manner (Black et al. 2007; Kim et al. 2009). Increased ICAM-1 and MHC-II expression on keratinocytes are also associated with many cutaneous diseases including psoriasis, AD, and delayed hypersensitivity reactions (Albanesi et al. 2005; Fan et al. 2003). In addition, keratinocytes might also express CD80 costimulatory molecule when exposed to specific allergens such as nickel chloride, oxazolone and Balsam of Peru and irritants such as treatment with IFN-γ plus 12-O-tetradecanoyl phorbol 13-acetate ester, sodium lauryl sulfate, dimethyl sulfoxide and phenol) (Wakem et al. 2000). CD80 can participate in the breaking of immunologic tolerance of the skin in AD and irritant contact dermatitis (Wakem et al. 2000). Similarly, in addition to playing a role in melanin production, melanocytes also express TLRs, MHC-II and immunoregulatory cytokines (Hong et al. 2015), indicating their function in immune system as nonprofessional APCs.