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Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
When infected with a protozoan, a host’s innate immune system must rapidly detect and respond to the parasite. Failure to do so allows the parasite to overwhelm the host, with disease and possibly death as likely outcomes. In this way, the response to protozoa is no different from the response to other microparasites. For many years it was unclear how the initial detection was achieved. In the past few decades it has become apparent that various immune system cells bear pattern recognition receptors (PRRs) that recognize certain molecules associated with specific groups of pathogens (PAMPs). As previously described in terms of their function in the plant immunoresponse, PAMPs essentially act as “danger signals”, alerting the immune system that a certain type of infection has occurred.
Infection and Inflammation
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Erik H. J. G. Aarntzen, Andor W. J. M. Glaudemans
Although inflammatory responses can be triggered by physical or chemical stimuli, with in general overlapping characteristics, this chapter focuses on the response on pathogenic stimuli such as bacteria, viruses, and parasites. Pathogenic microorganisms elicit an immunological response once they have crossed the epithelial barriers – for example, skin, mucosal lining of the gastro-intestinal tract, or the respiratory system. At these large surface areas, cells of the innate immune system, such as neutrophils and tissue resident macrophages (e.g. Kupffer cells, Langerhans cells, alveolar macrophages) are actively surveilling [1-3]. Although these cells lack the specificity of the adaptive immune system, they express pattern-recognition receptors that recognize classes of molecules present on pathogens. For example, toll-like receptors (TLRs) recognize molecular patterns that are not found in normal vertebrates – for example, lipopolysaccharide (LPS), a component of bacterial cell wall that is recognized by TLR-4. Mannose receptors are expressed on macrophages to recognize sugar molecules present on most bacteria and some viruses. Scavenger receptors bind negatively charged cell-wall components from gram-positive bacteria, such as lipoteichoic acid.
Senses matter: Senses protect integrity, connection and coherence
Published in Johanna Lynch, A Whole Person Approach to Wellbeing, 2020
Cellular descriptions of ‘sensing’ include intracellular ‘mitochondrial oxygen sensing’ (Bell, Emerling, and Chandel 2005), nutrient sensing (Sekine et al. 1994) and the innate immune ‘sense of danger’ (Hato and Dagher 2015) from non-self (infection) or damaged self (tissue injury). This is described as a ‘highly sophisticated sentinel system’ (Hato and Dagher 2015, 1459) that includes antibodies, pentraxins (e.g., C-reactive protein), the complement system, immune cells (macrophages, dendritic and killer cells) and epithelial cells (that produce cytokines and chemokines). Immune researchers also note what they have termed ‘pattern-recognition receptors’ that are have specific recognition processes that are part of innate immunity (Kawai and Akira 2010).
Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy
Published in OncoImmunology, 2022
Hyein Jeong, So-Young Lee, Hyejun Seo, Dong Hyun Kim, Duhyung Lee, Bum-Joon Kim
Pattern recognition receptors (PRRs) can lead to both maturation and activation of APCs via recognition by pathogen-associated molecular patterns (PAMPs) from external pathogens or damage-associated molecular patterns (DAMPs) from damaged tissues.17 Therefore, major efforts have been made to find a novel proper PAMP as an immunoadjuvant capable of sufficiently activating DCs for cancer immunotherapy. Of these PRRs, a total of four types of pattern recognition receptors (PRRs) have been identified, including C-type lectin receptors (CLRs), RIG I-like receptors (RLRs), NOD-like receptors (NLRs), and Toll-like receptors (TLRs).18,19 Of these, TLR4 is a member of TLRs first found in humans that can recognize lipopolysaccharide (LPS), a component present in gram-negative bacteria,20 and significant efforts have also been focused on the potential of its ligands as immunoadjuvants for DC-based vaccines.
Toll-like receptor agonist combinations augment mouse T-cell anti-tumor immunity via IL-12- and interferon ß-mediated suppression of immune checkpoint receptor expression
Published in OncoImmunology, 2022
Donghwan Jeon, Douglas G. McNeel
Certain pathogens can induce robust immune responses, which serves as the basis for using them as either delivery vehicles for vaccine antigens, or as vaccine adjuvants. The recent adenovirus vaccine developed by Janssen for SARS-CoV-2 serves as an example.12 This vaccine leads to a rapid innate immune response that is related to the activation of pattern recognition receptors (PRRs), such as toll-like receptors (TLRs). TLRs are transmembrane receptor proteins, which activate the innate immune system by sensing pathogen associated molecules.13 Ten different TLRs have been identified in humans and mice (TLR1-10 for humans, TLR1-9, and 13 for mice). They are expressed on macrophages, dendritic cells, T-cells, and B cells, as well as nonimmune cells, such as epithelial cells or fibroblasts.14–17 Each TLR recognizes a different type of biomolecule, and stimulation leads to the activation of innate and adaptive immune responses. Like other agents, chemical agonists for TLRs have been widely explored as adjuvants for traditional vaccines.18 Many investigators have also evaluated TLR agonists as adjuvants for anti-cancer vaccines. For example, HPV E7 oncoprotein-derived peptide vaccines showed antigen-specific T-cell activation and subsequent regression of HPV-driven tumors in mice when the vaccines were combined with TLR3 or TLR9 agonists.19 Combination of cancer-specific DNA vaccines targeting HPV E7 with either TLR3 or TLR7 ligands, or TLR4 agonists, similarly demonstrated greater antitumor responses in murine tumors.20,21
Naltrexone at low doses (LDN) and its relevance to cancer therapy
Published in Expert Review of Anticancer Therapy, 2022
The similarity between opioid receptors and other GPCRs suggests the possibility of other receptors being responsible for naltrexone action. Therefore, disruption of signaling via receptors of the same super-family or those that modify signaling through them is also thought to contribute to the mechanism by which naltrexone imparts its immune-modulatory effects. One such receptor that has been described to be part of this response is a distinct class of pattern-recognition receptors called the toll-like receptors. These have a central role in initiating immune responses by serving to recognize specific cellular and molecular patterns of cells damaged by pathogens. Activation of these TLRs, which exist in different classes, varies according to the stimulus, leads ultimately to changes to signaling cascades that orchestrate an immune response.