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Molecular Mechanisms of an Aberrant Specific Immune Response: Role in Pathogenesis of Infectious, Autoimmune Diseases and Cancer

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 28239

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Dr. Svetlana Khaiboullina

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Guest Editor

Institute of Fundamental Medicine and Biology, Kazan Federal University, OpenLab, 420008 Kazan, Russia
Interests: immune response; cytotoxic T cells; B cells; antibodies; autoantibodies; cytokines; antibody dependent cytotoxicity; pathogen associated molecular patterns; pathogen recognition receptors
Special Issues, Collections and Topics in MDPI journals

Dr. Ekaterina Martynova

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Guest Editor

Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Tatarstan, Russia
Interests: immune response; infections; autoimmune response
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The aim of a specific immune response is protection against infection and cancer while supporting repair and limiting tissue damage. A specific immune response is initiated upon exposure to a pathogen recognition pattern, damage-associated molecular pattern molecules, and tumor-associated antigens. These ligands are sensed by the pattern recognition receptors, initiating a specific immune response. This immune response involves the successful clearance of pathogens or abnormal host cells and establishes immune memory. However, in some circumstances, this specific immune response can target host tissues, damaging normal structures. This abberant immune response can maintain and extend destruction, imparing the function of tissues and organs. Impaired organ function can impact a patient’s longevity and the quality of a patient’s life. We invite authors to submit original research papers and review articles related to the following potential list of topics:

Aberrant molecular mechanisms of T and B lymphocyte development, activation, and function in infection, autoimmunity, and cancer;
The role of bioactive molecules (cytokines, chemokines, interferons, growth factors) in aberrant immune responses;
Role of antibody-dependent cytotoxicity in tissue damage and the failure of immune protection;
Genetic markers of aberrant immune responses;
Role of antibodies and autoantibodies in aberrant immune responses;
Role of PAMPS, DAMPS, and PRR in immune responses to infection, autoimmunity, and cancer.

Dr. Svetlana Khaiboullina
Dr. Ekaterina Martynova
Guest Editors

Manuscript Submission Information

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Keywords

immune response
cytotoxic T cells
B cells
antibodies
autoantibodies
cytokines
antibody dependent cytotoxicity
virus
microbe
pathogen-associated molecular patterns
pathogen recognition receptors

Published Papers (7 papers)

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Research

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14 pages, 1343 KiB

Open AccessCommunication

Neutralizing Antibodies in COVID-19 Serum from Tatarstan, Russia

by Shaimaa Hamza, Ekaterina Martynova, Ekaterina Garanina, Venera Shakirova, Alisa Bilalova, Svetlana Moiseeva, Ilsiyar Khaertynova, Olesia Ohlopkova, Nataliya Blatt, Maria Markelova and Svetlana Khaiboullina

Int. J. Mol. Sci. 2023, 24(12), 10181; https://doi.org/10.3390/ijms241210181 - 15 Jun 2023

Viewed by 943

Abstract

The severity of COVID-19 is a result of the complex interplay between various branches of the immune system. However, our understanding of the role of neutralizing antibodies and the activation of cellular immune response in COVID-19 pathogenesis remains limited. In this study, we investigated neutralizing antibodies in patients with mild, moderate, and severe COVID-19, analyzing their cross-reactivity with the Wuhan and Omicron variants. We also assessed the activation of the immune response by measuring serum cytokines in patients with mild, moderate, and severe COVID-19. Our findings suggest the early activation of neutralizing antibodies in moderate COVID-19 compared to mild cases. We also observed a strong correlation between the cross-reactivity of neutralizing antibodies to the Omicron and Wuhan variants and the severity of the disease. In addition, we found that Th1 lymphocyte activation was present in mild and moderate cases, while inflammasomes and Th17 lymphocytes were activated in severe COVID-19. In conclusion, our data indicate that the early activation of neutralizing antibodies is evident in moderate COVID-19, and there is a strong correlation between the cross-reactivity of neutralizing antibodies and the severity of the disease. Our findings suggest that the Th1 immune response may play a protective role, while inflammasome and Th17 activation may be involved in severe COVID-19. Full article

(This article belongs to the Special Issue Molecular Mechanisms of an Aberrant Specific Immune Response: Role in Pathogenesis of Infectious, Autoimmune Diseases and Cancer)

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18 pages, 2949 KiB

Open AccessArticle

Interaction of Bacteria, Immune Cells, and Surface Topography in Periprosthetic Joint Infections

by Cristina Belgiovine, Luca Pellegrino, Alberto Bulgarelli, Francesca Cecilia Lauta, Alessia Di Claudio, Roberta Ciceri, Assunta Cancellara, Francesca Calcaterra, Domenico Mavilio, Guido Grappiolo, Katia Chiappetta, Mattia Loppini and Roberto Rusconi

Int. J. Mol. Sci. 2023, 24(10), 9028; https://doi.org/10.3390/ijms24109028 - 19 May 2023

Cited by 4 | Viewed by 1324

Abstract

The incidence of periprosthetic joint infections (PJIs) is ~2% of total procedures and it is expected to rise due to an ageing population. Despite the large burden PJI has on both the individual and society, the immune response to the most commonly isolated pathogens, i.e., Staphylococcus aureus and Staphylococcus epidermidis, remains incompletely understood. In this work, we integrate the analysis of synovial fluids from patients undergoing hip and knee replacement surgery with in-vitro experimental data obtained using a newly developed platform, mimicking the environment of periprosthetic implants. We found that the presence of an implant, even in patients undergoing aseptic revisions, is sufficient to induce an immune response, which is significantly different between septic and aseptic revisions. This difference is confirmed by the presence of pro- and anti-inflammatory cytokines in synovial fluids. Moreover, we discovered that the immune response is also dependent on the type of bacteria and the topography of the implant surface. While S. epidermidis seems to be able to hide better from the attack of the immune system when cultured on rough surfaces (indicative of uncemented prostheses), S. aureus reacts differently depending on the contact surface it is exposed to. The experiments we performed in-vitro also showed a higher biofilm formation on rough surfaces compared to flat ones for both species, suggesting that the topography of the implant could influence both biofilm formation and the consequent immune response. Full article

(This article belongs to the Special Issue Molecular Mechanisms of an Aberrant Specific Immune Response: Role in Pathogenesis of Infectious, Autoimmune Diseases and Cancer)

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11 pages, 2182 KiB

Open AccessArticle

Lateral Flow Immunoassay Based on Time-Resolved Fluorescence Microspheres for Rapid and Quantitative Screening CA199 in Human Serum

by Xueshima Jiao, Tao Peng, Zhanwei Liang, Yalin Hu, Bo Meng, Yang Zhao, Jie Xie, Xiaoyun Gong, You Jiang, Xiang Fang, Xiaoping Yu and Xinhua Dai

Int. J. Mol. Sci. 2022, 23(17), 9991; https://doi.org/10.3390/ijms23179991 - 01 Sep 2022

Cited by 4 | Viewed by 1908

Abstract

Carbohydrate antigen 199 (CA199) is a serum biomarker which has certain value and significance in the diagnosis, prognosis, treatment, and postoperative monitoring of cancer. In this study, a lateral flow immunoassay based on europium (III) polystyrene time-resolved fluorescence microspheres (TRFM-based LFIA), integrated with a portable fluorescence reader, has been successfully establish for rapid and quantitative analysis of CA199 in human serum. Briefly, time-resolved fluorescence microspheres (TRFMs) were conjugated with antibody I (Ab1) against CA199 as detection probes, and antibody II (Ab2) was coated as capture element, and a “TRFMs-Ab1-CA199-Ab2” sandwich format would form when CA199 was detected by the TRFM-based LFIA. Under the optimal parameters, the detection limit of the TRFM-based LFIA for visible quantitation with the help of an ultraviolet light was 4.125 U/mL, which was four times lower than that of LFIA based on gold nanoparticles. Additionally, the fluorescence ratio is well linearly correlated with the CA199 concentration (0.00–66.0 U/mL) and logarithmic concentration (66.0–264.0 U/mL) for quantitative detection. Serum samples from 10 healthy people and 10 liver cancer patients were tested to confirm the performances of the point-of-care application of the TRFM-based LFIA, 20.0 U/mL of CA199 in human serum was defined as the threshold for distinguishing healthy people from liver cancer patients with an accuracy of about 60%. The establishment of TRFM-based LFIA will provide a sensitive, convenient, and efficient technical support for rapid screening of CA199 in cancer diagnosis and prognosis. Full article

(This article belongs to the Special Issue Molecular Mechanisms of an Aberrant Specific Immune Response: Role in Pathogenesis of Infectious, Autoimmune Diseases and Cancer)

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Review

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13 pages, 1348 KiB

Open AccessReview

Regulation of the Host Immune Microenvironment in Periodontitis and Periodontal Bone Remodeling

by Nannan Han, Yitong Liu, Juan Du, Junji Xu, Lijia Guo and Yi Liu

Int. J. Mol. Sci. 2023, 24(4), 3158; https://doi.org/10.3390/ijms24043158 - 05 Feb 2023

Cited by 3 | Viewed by 2571

Abstract

The periodontal immune microenvironment is a delicate regulatory system that involves a variety of host immune cells including neutrophils, macrophages, T cells, dendritic cells and mesenchymal stem cells. The dysfunction or overactivation of any kind of local cells, and eventually the imbalance of the entire molecular regulatory network, leads to periodontal inflammation and tissue destruction. In this review, the basic characteristics of various host cells in the periodontal immune microenvironment and the regulatory network mechanism of host cells involved in the pathogenesis of periodontitis and periodontal bone remodeling are summarized, with emphasis on the immune regulatory network that regulates the periodontal microenvironment and maintains a dynamic balance. Future strategies for the clinical treatment of periodontitis and periodontal tissue regeneration need to develop new targeted synergistic drugs and/or novel technologies to clarify the regulatory mechanism of the local microenvironment. This review aims to provide clues and a theoretical basis for future research in this field. Full article

(This article belongs to the Special Issue Molecular Mechanisms of an Aberrant Specific Immune Response: Role in Pathogenesis of Infectious, Autoimmune Diseases and Cancer)

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26 pages, 3833 KiB

Open AccessReview

Molecular Mechanisms of RSV and Air Pollution Interaction: A Scoping Review

by August Wrotek and Teresa Jackowska

Int. J. Mol. Sci. 2022, 23(20), 12704; https://doi.org/10.3390/ijms232012704 - 21 Oct 2022

Cited by 4 | Viewed by 2916

Abstract

RSV is one of the major infectious agents in paediatrics, and its relationship with air pollution is frequently observed. However, the molecular basis of this interaction is sparsely reported. We sought to systematically review the existing body of literature and identify the knowledge gaps to answer the question: which molecular mechanisms are implied in the air pollutants–RSV interaction? Online databases were searched for original studies published before August 2022 focusing on molecular mechanisms of the interaction. The studies were charted and a narrative synthesis was based upon three expected directions of influence: a facilitated viral entry, an altered viral replication, and an inappropriate host reaction. We identified 25 studies published between 1993 and 2020 (without a noticeable increase in the number of studies) that were performed in human (n = 12), animal (n = 10) or mixed (n = 3) models, and analysed mainly cigarette smoke (n = 11), particulate matter (n = 4), nanoparticles (n = 3), and carbon black (n = 2). The data on a damage to the epithelial barrier supports the hypothesis of facilitated viral entry; one study also reported accelerated viral entry upon an RSV conjugation to particulate matter. Air pollution may result in the predominance of necrosis over apoptosis, and, as an effect, an increased viral load was reported. Similarly, air pollution mitigates epithelium function with decreased IFN-γ and Clara cell secretory protein levels and decreased immune response. Immune response might also be diminished due to a decreased viral uptake by alveolar macrophages and a suppressed function of dendritic cells. On the other hand, an exuberant inflammatory response might be triggered by air pollution and provoke airway hyperresponsiveness (AHR), prolonged lung infiltration, and tissue remodeling, including a formation of emphysema. AHR is mediated mostly by increased IFN-γ and RANTES concentrations, while the risk of emphysema was related to the activation of the IL-17 → MCP-1 → MMP-9 → MMP-12 axis. There is a significant lack of evidence on the molecular basics of the RSV–air pollution interaction, which may present a serious problem with regards to future actions against air pollution effects. The major knowledge gaps concern air pollutants (mostly the influence of cigarette smoke was investigated), the mechanisms facilitating an acute infection or a worse disease course (since it might help plan short-term, especially non-pharmacological, interventions), and the mechanisms of an inadequate response to the infection (which may lead to a prolonged course of an acute infection and long-term sequelae). Thus far, the evidence is insufficient regarding the broadness and complexity of the interaction, and future studies should focus on common mechanisms stimulated by various air pollutants and a comparison of influence of the different contaminants at various concentrations. Full article

(This article belongs to the Special Issue Molecular Mechanisms of an Aberrant Specific Immune Response: Role in Pathogenesis of Infectious, Autoimmune Diseases and Cancer)

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24 pages, 2739 KiB

Open AccessReview

Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Use in Central Nervous System Demyelinating Disorders

by Caterina Allegretta, Emanuele D’Amico, Virginia Manuti, Carlo Avolio and Massimo Conese

Int. J. Mol. Sci. 2022, 23(7), 3829; https://doi.org/10.3390/ijms23073829 - 30 Mar 2022

Cited by 7 | Viewed by 3429

Abstract

Autoimmune demyelinating diseases—including multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein-associated disease, acute disseminated encephalomyelitis, and glial fibrillary acidic protein (GFAP)-associated meningoencephalomyelitis—are a heterogeneous group of diseases even though their common pathology is characterized by neuroinflammation, loss of myelin, and reactive astrogliosis. The lack of safe pharmacological therapies has purported the notion that cell-based treatments could be introduced to cure these patients. Among stem cells, mesenchymal stem cells (MSCs), obtained from various sources, are considered to be the ones with more interesting features in the context of demyelinating disorders, given that their secretome is fully equipped with an array of anti-inflammatory and neuroprotective molecules, such as mRNAs, miRNAs, lipids, and proteins with multiple functions. In this review, we discuss the potential of cell-free therapeutics utilizing MSC secretome-derived extracellular vesicles—and in particular exosomes—in the treatment of autoimmune demyelinating diseases, and provide an outlook for studies of their future applications. Full article

(This article belongs to the Special Issue Molecular Mechanisms of an Aberrant Specific Immune Response: Role in Pathogenesis of Infectious, Autoimmune Diseases and Cancer)

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10 pages, 1209 KiB

Open AccessReview

Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases

by Agata Buonacera, Benedetta Stancanelli, Michele Colaci and Lorenzo Malatino

Int. J. Mol. Sci. 2022, 23(7), 3636; https://doi.org/10.3390/ijms23073636 - 26 Mar 2022

Cited by 198 | Viewed by 14431

Abstract

Over the last 10 years, the evaluation of the neutrophil-to-lymphocyte ratio (NLR) as an emerging marker of diseases has become a compelling field of bio-medical research. Although a precise and unique cut-off value has not been yet found, its role as a flag of immune system homeostasis is well established. NLR has a well-known prognostic value and independently correlates with mortality in the general population and in several specific subsets of disease (sepsis, pneumonia, COVID-19, cancer, etc.). Moreover, NLR was recently considered as part of the decision-making processes concerning the admission/recovery of patients with COVID-19 pneumonia. This review aims to provide an overview of the main use of this biomarker, focusing on the pathophysiology and the molecular basis underlying its central role as a reliable mirror of inflammatory status and adaptive immunity. Full article

(This article belongs to the Special Issue Molecular Mechanisms of an Aberrant Specific Immune Response: Role in Pathogenesis of Infectious, Autoimmune Diseases and Cancer)

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