Immunological risks caused by silica particles.
\r\n\tThe book aims to introduce the potential reader to the problems associated with aeronautics, ranging from academic research to actual application and precise work, and to be of interest to those who want to research and build their techniques in the related fields.
",isbn:"978-1-80355-301-6",printIsbn:"978-1-80355-300-9",pdfIsbn:"978-1-80355-302-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"a6b8e86015392b400a37551116fc0c13",bookSignature:"Associate Prof. Zain Anwar Anwar Ali",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11522.jpg",keywords:"Aeronautics, Aircraft, Control System, Surveillance, Guidance, Fixed-Wing, Rotorcraft, Jet Engine, Modern Drone, Path Planning, Adaptive Control, Hybrid Control",numberOfDownloads:15,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2022",dateEndSecondStepPublish:"April 12th 2022",dateEndThirdStepPublish:"June 11th 2022",dateEndFourthStepPublish:"August 30th 2022",dateEndFifthStepPublish:"October 29th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Engr. Dr. Zain Anwar Ali is working as an Associate Prof. and Editor of Sir Syed University Research Journal of Engineering and Technology. He received research funding from Higher Education Commission (HEC), Pakistan, and has research collaborations with several universities in China, including Nanjing University of Aeronautics and Astronautics, Donghua University, Shanghai University, and South East University, under different research grants provided by the National Nature Science Foundation of China.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"415526",title:"Associate Prof.",name:"Zain",middleName:"Anwar",surname:"Anwar Ali",slug:"zain-anwar-ali",fullName:"Zain Anwar Ali",profilePictureURL:"https://mts.intechopen.com/storage/users/415526/images/system/415526.png",biography:"Engr. Dr. Zain Anwar Ali received his B.S. degree in Electronic Engineering from Sir Syed University of Engineering and Technology, Karachi, Pakistan, in 2009. In the same year, he joined Sir Syed UET as a Research Assistant in the Electronic Engineering department, and was soon promoted to a Junior Lecturer due to his hard work and research contributions. He completed his Master's in Industrial Control and Automation at the Hamdard University of Engineering in 2012, securing his second position and soon being promoted to a Lecturer. Later he joined Nanjing University of Aeronautics and Astronautics (NUAA) as a Ph.D. research scholar and the Nanjing Strong Flight Electronics and Machinery LTD to complete his Ph.D. experimental work there. In 2017, he completed his Ph.D. in the field of Control Theory and Control Engineering NUAA. He then rejoined Sir Syed UET as an Assistant Professor in the Electronics Engineering department. In the same year, he was selected as a highly talented foreign expert by the Ministry of China, Beijing, at Liaocheng. After seeing his research background, the vice-chancellor of SSUET gave him the extra responsibility of an Associate Editor of Sir Syed UET research journal which is indexed at various indexing agencies and published in two issues annually. In 2018-2019, he received research funding from Higher Education Commission (HEC), Pakistan, and started some different research collaborations with several universities in China, including Nanjing University of Aeronautics and Astronautics (NUAA-Nanjing), Donghua University (DU-Shanghai), Shanghai University (SU-Shanghai), and South East University (SEU-Nanjing), under different research grants provided by the National Nature Science Foundation of China (NSFC). Currently, Dr. Ali is working as an Associate Professor at the Electronic Engineering Department, Sir Syed University of Engineering and Technology, Karachi, Pakistan, and as the Editor of Sir Syed University Research Journal of Engineering and Technology.",institutionString:"Sir Syed University of Engineering and Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Sir Syed University of Engineering and Technology",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:[{id:"82261",title:"Military Aircraft Flight Control",slug:"military-aircraft-flight-control",totalDownloads:14,totalCrossrefCites:0,authors:[null]},{id:"82328",title:"The Impact of the Pandemic Effect on the Aviation in the Environmental Quality of the Air Transport and Travelers",slug:"the-impact-of-the-pandemic-effect-on-the-aviation-in-the-environmental-quality-of-the-air-transport-",totalDownloads:1,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"347258",firstName:"Marica",lastName:"Novakovic",middleName:null,title:"Ms.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"marica@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"10198",title:"Response Surface Methodology in Engineering Science",subtitle:null,isOpenForSubmission:!1,hash:"1942bec30d40572f519327ca7a6d7aae",slug:"response-surface-methodology-in-engineering-science",bookSignature:"Palanikumar Kayaroganam",coverURL:"https://cdn.intechopen.com/books/images_new/10198.jpg",editedByType:"Edited by",editors:[{id:"321730",title:"Prof.",name:"Palanikumar",surname:"Kayaroganam",slug:"palanikumar-kayaroganam",fullName:"Palanikumar Kayaroganam"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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In addition to pulmonary effects, such as fibrosis, chronic inflammations, and cancers, such as lung malignancies and pleural mesothelioma, in asbestos-exposed patients, there may be certain effects on immunological cells [11–16]. Among people who have been exposed to asbestos fibers or silica particles, people exposed to silica and have developed silicosis often suffer from complicated autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis, and antineutrophil cytoplasmic antigen (ANCA)–related vasculitis [17–20]. The core chemical components of asbestos fibers are Si and O2, and although the physical makeup of fibrous and particulate matter differs, asbestos fibers may affect the immune system. Therefore, we have been investigating the immunological effects of silica and asbestos [11–16].
\nRegarding silica particles, the mechanism of silica-induced dysregulation of autoimmunity is thought to involve silica acting as an adjuvant [21–24]. However, silica particles may also act by directly stimulating on circulating peripheral immune cells, which cause certain alterations in the cellular or molecular functions of these cells, since silica particles may remain in pulmonary lesions and lymph nodes after inhalation [11–16]. Since these direct effects may change the characteristics of immune cells and consequently facilitate the dysregulation of immune tolerance, clarification of these cellular and molecular mechanisms may be useful in the prevention of immune disorders that occur in silicosis patients (SIL), in addition to contributing toward an understanding of the etiology of various autoimmune diseases.
\nWe have been focusing on the immunological effects of silica using human peripheral blood immune cells derived from healthy donors (HD) and SIL [11–14]. We will summarize our findings which indicate that silica is an environmental immune stimulator, and chronic activation of immune cells induced by recurrent and chronic exposure to silica causes an imbalance in the regulation of T cell responses.
\nRegarding asbestos fibers, asbestos-related cancers, such as malignant mesothelioma (MM) and lung cancer, have been a major global concern in Japan [25–29]. Given the conflict that has arisen due to economic considerations and the medical evidence, there is a confusion concerning the pathological mechanisms of asbestos-induced cancers, and in particular, an uncertainty concerning the dangers of iron-absent chrysotile (white) asbestos compared with iron-present crocidolite (blue) and amosite (brown) asbestos [30–33]. However, regarding the poor prognosis of MM, novel medical approaches to investigate the biological effects of asbestos and pathological mechanisms of asbestos-induced carcinogenesis, as well as clinical trials to detect early stages of MM, should be implemented to assist in the development of improved prevention strategies and cure of asbestos-related malignancies [34–36]. From this standpoint, our group has been investigating the immunological effects of asbestos with respect to the reduction of tumor immunity [11, 12, 15, 16]. In this chapter, cellular and molecular approaches to clarify the immunological effects of asbestos are described, and all findings indicate that a reduction of tumor immunity is caused by asbestos exposure and is involved in asbestos-induced cancers. In addition to confirming the well-known biological effects of asbestos, these investigations provide a basis for the development of a novel procedure for the early detection of previous asbestos exposure, mesothelioma and the chemoprevention of asbestos-related cancers.
\nAs shown in Figure 1, both silica particles and asbestos fibers cause pulmonary fibrosis known as pneumoconiosis, silicosis, and asbestosis. Additionally, both can affect various immune cells, such as B cells, CD4 T helper (Th1), regulatory T (Treg), cytotoxic T lymphocyte (CTL), natural killer (NK) cells, and other immune cells [11, 12, 15, 16].
\nSchematic representation of immunological risks caused by exposure to silica particles and asbestos fibers. The immunological risks induced crucial complications, such as autoimmune diseases, in silicosis patients, as well as malignant tumors, such as lung cancer and malignant mesothelioma, in asbestos-exposed populations.
In this chapter, the immunological effects on various immune cells caused by silica particles and asbestos fibers as investigated in our laboratory will be presented and discussed with respect to the detection of immunological risks of particulate and fibrous environmental factors [11–16]. These summarized findings may be helpful in the development of future risk management strategies, including cases related to newly developed fibrous and particulate matter, such as nanoparticles and nanotubes.
\nAs shown in Table 1, there are various immunological risks associated with exposure to silica particles. These findings were established by in vitro assays using peripheral blood mononuclear cells (PBMC) derived from HD cultured with silica particles as well as freshly isolated immune cells derived from SIL. Additionally, various autoantibodies (aAbs) were detected from SIL [11–14]. All SIL comprised Japanese workers of a firebrick factory located at Bizen City, Okayama Prefecture, Japan, diagnosed with silicosis according to the International Labor Organization (ILO) 2000 guidelines for pneumoconiosis and monitored at Kusaka Hospital or Hinase Urakami Iin/Clinic at Bizen City. All SIL showed no symptoms related to autoimmune diseases or cancers.
\nRisk manifestation | \nTarget cells/molecules | \nFindings | \nReferences | \n
---|---|---|---|
Unusual autoantibody | \nB cell | \nDetection of autoantibodies against | \n|
\n | \n | ➢ Fas/CD95 | \n61 | \n
\n | \n | ➢ Caspase 8 | \n62 | \n
\n | \n | ➢ Scl-70/Topoisomerase I | \n56–58 | \n
\n | \n | ♦ Specific HLA type | \n\n |
\n | \n | ➢CENP-B/centromere | \n64 | \n
\n | \n | ➢Desmoglein | \n65 | \n
Dysregulated apoptosis | \nT cell | \nIncreased level of molecules against | \n\n |
\n | \n | Fas-mediated apoptosis | \n\n |
\n | \n | ➢ Soluble Fas | \n|
\n | \n | ♦ Serum soluble Fas | \n69 |
\n | \n | ♦ mRNA expression in PBMC | \n70 |
\n | \n | ➢ Variant Fas, alternatively spliced variants | \n71 |
\n | \n | ➢ Decoy receptor 3 | \n74 | \n
\n | \n | ♦ mRNA expression in PBMC | \n\n |
\n | \n | Chronic activation | \n80 |
\n | \n | ➢ Soluble IL-2 receptor | \n78 |
\n | \n | ➢ PD-1 expression | \n79 |
\n | \n | ➢ CD69 surface expression | \n|
\n | \n | Increase in Fas-mediated apoptosis | \n61 |
\n | \n | ➢ Autoantibody for Fas | \n75 |
\n | \n | ➢ Decreased expression of physiological inhibitors of Fas-mediated apoptosis | \n|
\n | Regulatory T cell | \nChronic activation | \n|
\n | \n | ➢ Excess expression of Fas/CD95 | \n>78 | \n
Immunological risks caused by silica particles.
IL, interleukin; PBMC, peripheral blood mononuclear cells; and PD-1, program death protein 1
First, the risk of dysregulated autoimmunity assessed by the detection of particular aAbs will be discussed. Various aAbs have been detected in SIL, such as antinuclear antibody (ANA) [37–40], antismooth muscle aAb [41], antiglomerular basement membrane (GBM) aAb [41], antineutrophil cytoplasmic aAb (MPO-ANCA) [37, 42–48], rheumatoid factor (RF) [37–39, 49–53], anti-Scl-70/topoisomerase I aAb [37, 54–60], anti-Fas/CD95 aAb [61], anticaspase 8 aAb [62], anticentromere/CENP-B (centromere protein B) aAb [63], antidesmoglein aAb [64], anti-PL 12 (aminoacyl tRNA synthetase) aAb [65], and anticollagen aAb [39], as found in publications located via PubMed.
\nOf these aAbs, we investigated several Abs of interest, such as anti-Fas/CD95 Ab [61], anticaspase 8 Ab [62], anti-Scl-70 Ab with respect to specific human leukocyte antigen (HLA) types [56–58], and anti-CENP-B Ab [63] and reported the case of antidesmoglein Ab-positive SIL [64].
\nWe detected anti-Fas/CD95 aAb in approximately one-fourth of SIL [61]. Since T cells in SIL tend to be categorized into two classes, Fas/CD95-mediated apoptosis prone and resistant groups as described later in this chapter, it is important to determine whether the detected anti-Fas/CD95 aAb is functional in terms of the induction of Fas/CD95-mediated apoptosis. To examine this issue, we employed our established human sister myeloma cell lines, KMS-12PE and KMS-12BM. The former cell line was established from the pleural effusion of a myeloma patient, which showed high expression of Fas/CD95 on its surface as a result of apoptosis and growth inhibition caused by anti-Fas/CD95 agonistic antibody. The latter cell line was derived from bone marrow obtained from the same patients, who showed very low expression of Fas/CD95 and no apoptosis caused by Fas/CD95 agonistic antibody [66]. Following cultivation of both cell lines with anti-Fas/CD95 aAb-positive serum from SIL, the growth of KMS-12PE was reduced by apoptosis, whereas the growth of KMS-12BM was unaffected [61]. These results indicated that anti-Fas/CD95 aAb is functional. Additionally, epitope mapping employing 12-amino acid polypeptides with the SPOT system of anti-Fas/CD95 aAb was analyzed. As a result, a minimum of four and a maximum of ten epitopes were found, and several amino acid residues involved in binding Fas ligand, such as C66, R87, L90 E93, and H126, were identified [61].
\nAs in the case of anti-Fas/CD95 aAb, anticaspase 8 aAb was investigated in terms of the dysregulation of Fas/CD95-mediated apoptosis of lymphocytes in SIL [62]. The association of anticaspase 8 aAb with HLA types was examined. As a result, the frequencies of HLA-DRB1*0406 were significantly higher in aAb-positive SIL (16.7%) compared with control individuals (3.0%, p<0.001). Additionally, HLA-DR4; DQB1*0302 was found in one-fourth of positive SIL, and DPB1*0601 was also higher in positive SIL (5.9%) compared with controls (0.6%, p<0.05), whereas DQB1*0401 was lower in positive SIL (0%) compared with controls (13.3%, p<0.001). Furthermore, epitope mapping showed that a minimum of four and a maximum of thirteen polypeptides seemed to be involved. Among these, two important catalytic cysteine residues were found, cysteine Cys287 and Cys360, located in the unique pentapeptide motif QACQG [62].
\nRegarding the relationship between aAb and specific HLA type, we reported HLA types among anti-Scl70/topoisomerase I aAb-positive SIL [56–58]. Results indicated that the allelic frequency of HLA-DQB1*0402 was significantly higher in aAb-positive SIL (28.6%) than in aAb-negative SIL (1.5%, p<0.001), as well as in controls (0.8%, p<0.001). Additionally, DQDB1*0301, DQB1*0601, and DPB1*1801 were higher in aAb-positive SIL than in aAb-negative SIL, whereas no significant differences were found compared with controls [56–58].
\nIn terms of anti-CENP-B/centromere aAb, the titer index (Log10) of anti-CENP-B autoantibody in SIL was higher than that of HV, and patients with systemic sclerosis (SSc) was higher than those of HV and SIL. This titer index was positively correlated with an assumed immune status for HV as 1, SIL as 2, and SSc as 3. Moreover, although the titer index of anti-CENP-B autoantibody formed the same factor with anti-Scl-70 autoantibody, the Ig G value, and age of SIL, the property of other factors extracted indicated that anti-Scl-70 antibody was positively related with the Ig A value, while the converse was true for anti-CENP-B from the results of factor analysis. Those results indicated that the titer index of anti-CENP-B autoantibody may be employed as a biomarker in identifying dysregulation in SIL cases.
\nTaken together, various aAbs found in SIL have indicated that dysregulation of autoimmunity was caused by chronic and recurrent exposure to silica particles that remained in lung and related lymph nodes of various human cells, especially B cells. Some of these aAbs may be related to Fas/CD95-mediated apoptosis of lymphocytes and cause further dysregulation of autoimmunity such as in the case of long-surviving self-antigen recognizing clones in T cells [11–14].
\nFurthermore, examination of HLA types seemed to be important in revealing several aAbs in SIL. Although it can be mentioned that repeated and continuous screening of aAbs as well as the initial screening of HLA types seems to be necessary among workers in contact with silica-related substances for the detection of dysregulation of autoimmunity, the use of genotyping, such as determining HLA types, is not permitted during employee selection procedures. However, a consideration of particular occupational health risks together with individual sensitivities is required in an effort to prevent occupational health hazards and associated future hardships.
\nFas/CD95-related molecules analyzed in SIL are shown in Table 1 [11–14, 67]. Regarding molecules that inhibit Fas/CD95-mediated apoptosis, the level of soluble Fas/CD95 was higher in the serum of SIL compared with HD, and similar to the level in systemic lupus erythematosus (SLE) [68], while higher mRNA expression, determined as the ratio of soluble to wild-type Fas/CD95, was present in SIL compared with HD in PBMC [69]. Additionally, higher amounts of various alternatively spliced variant messages of the Fas/CD95 gene were detected in PBMC from SIL compared with HD [70]. All of these variant messages, including soluble Fas/CD95, possess a Fas ligand-binding domain but lack a membrane-binding domain. Hence all of these translation products are secreted into the extracellular space and bind with Fas ligand, thereby protecting cells against membrane Fas-mediated apoptosis [70]. Furthermore, the expression of the protective molecule decoy receptor 3 (DcR3), which acts against the Trail molecule and similarly induces apoptosis via a Trail receptor and the same intracellular signaling molecules for apoptosis, such as caspase 8 and 10 [71, 72], was higher in SIL PBMC compared with HD [73]. These findings indicated that some types of T cells in PBMC from SIL provide protection against Fas/CD95- and Trail-induced apoptosis, which leads to long survival of these T cells and self-antigen recognizing clones [67].
\nHowever, several findings that showed accelerated Fas/CD95- and Trail-mediated apoptosis in PBMC of SIL were investigated. Messenger RNA expression in PBMC of several genes which act as physiological inhibitors of Fas/CD95- and Trail-mediated apoptosis, such as I-Flice (inhibitor of FADD-like interleukin-1β–converting enzyme), surviving, sentrin, and inhibitor of caspase-activated DNase (ICAD) was lower in SIL compared with HD [67, 74]. In addition to the aforementioned detection of functional anti-Fas/CD95 autoantibody, some types of T cells in PBMC from SIL possess enhanced Fas/CD95-mediated apoptosis [61]. Further studies revealed that this fraction may include Treg cells [13, 14]. Thus, a decrease in the number of Treg cells by apoptosis and an increase in the number of responder T cells caused by silica exposure may be the cellular biological mechanisms at work in SIL, which consequently impart susceptibility to autoimmune diseases in SIL.
\nWe found higher expression of Fas/CD95 in Treg (CD4+, CD25+, and forkhead box P3 (FoxP3) +) [75, 76] and sensitivity to Fas-agonistic antibody–induced apoptosis in Treg cells from SIL [77]. Furthermore, when PBMC from HD were cultured with silica particles in vitro, Treg cell numbers were selectively reduced by apoptosis and the population of responder T cells was enhanced [77]. Thus, the aforementioned T cell population prone to Fas/CD95-mediated apoptosis seems to comprise Treg cells, and the imbalance that occurs as a result of a decreased Treg and surviving responder T cell population in SIL induces dysregulation of autoimmunity [13, 14, 77].
\nMoreover, there is evidence showing chronic activation of responder T cells. For example, CD69, an early activating marker of T cells, was gradually expressed in T cells when PBMC from HD were cultured in vitro with silica particles [78]. Expression of the program death protein 1 (PD-1) gene, another activation marker of T cells, in CD4+ CD25+ as well as in CD4+ CD25− T cell populations was higher in SIL compared with HD, which showed negligible expression [78]. Expression of serum soluble interleukin (IL)-2 receptor (sIL-2R) was also higher in SIL compared with HD [79].
\nTaken together, SIL possess a risk of developing dysregulation of autoimmunity. This risk can be detected using various markers mentioned above, such as serum soluble Fas, sIL-2R, and serum DcR3 (recently, the enzyme-linked immunosorbent assay (ELISA) kit is available for laboratory use), in SIL during their early clinical phases.
\nAs shown in Figure 1, the most important and critical complications that arise in asbestos-exposed patients concern the development of malignancies, such as lung cancer and MM [25–29]. Of course, asbestos fibers possess carcinogenic-related activities, such as oxygen stress caused by iron in the asbestos fibers, frustrated macrophages incapable of phagocytosing asbestos fibers, chromosome tangling, and the absorption of other carcinogenic substances inhaled in the lung, such as materials from tobacco smoke and other air pollutants [34–36]. However, given the long latency period that precedes the onset of MM following initial exposure to asbestos, it was considered that asbestos fibers cause alterations in antitumor immunity by recurrent and chronic encounters with various immune cells at the lung and related lymph nodes.
\nAs shown in Table 2, our findings show altered immune cell function and manifestations from experimental settings as well as PBMC derived from pleural plaque and MM [11, 12, 15, 16, 80, 81].
\nRisk manifestation | \nTarget cells | \nFindings | \nReferences | \n
---|---|---|---|
Innate Immune system | \nNK cells | \nReduction of cytotoxicity | \n|
\n | \n | ➢ Freshly isolated NK cells | \n|
\n | \n | ♦ NK cells from asbestos-exposed patients (PP and MM) | \n83–84 |
\n | \n | ♦ NK cells from HD stimulated in vitro with | \n83 |
\n | \n | asbestos | \n83 |
\n | \n | ➢ Human cell line cultured with asbestos | \n|
\n | \n | Reduced expression of NK cell activation receptor | \n83 |
\n | \n | ➢ Human cell line cultured with asbestos: NKG2D, 2B4 | \n83,84 |
\n | \n | ➢ Freshly isolated NK cells | \n|
\n | \n | ♦ NK cells from asbestos-exposed patients (PP and MM): NKp46 | \n83,84 |
\n | \n | ♦ NK cells from HD stimulated in vitro with asbestos: NKp46 | \n84 |
\n | \n | Reduction of phosphorylation of ERK 1/2 | \n|
\n | \n | ➢ Human cell line cultured with asbestos | \n\n |
MHC class I restricted killing System | \nCTLs | \nSuppressed differentiation and proliferation | \n\n |
\n | \n | ➢ In vitro assay using MLR with asbestos | \n85 | \n
\n | \n | Alteration of killing molecules (granzyme B, IFNγ, perforin) | \n\n |
\n | \n | ➢ In vitro assay using MLR with asbestos | \n86 | \n
\n | \n | ➢ Freshly isolated and in vitro stimulated peripheral | \n\n |
\n | \n | CD8+ cells from PP | \n86 | \n
\n | \n | ➢ Freshly isolated and in vitro stimulated peripheral | \n\n |
\n | \n | CD8+ cells from MM | \n\n |
MHC class II restricted killing system | \nTh1 cells | \nDecrease in CXCR3 expression, IFNγ | \n\n |
\n | \n | ➢ Cell line model continuously cultured with asbestos | \n87 | \n
\n | \n | ➢ Freshly isolated and cultured in vitro with asbestos from HD | \n88 | \n
\n | \n | ➢ Freshly isolated CD4+ T cells from PP and MM | \n88 | \n
Regulation of T cell response | \nRegulatory T (Treg) cells | \nEnhanced function | \n\n |
\n | \n | ➢ Cell line model continuously cultured with asbestos | \n\n |
\n | \n | ♦ Increased suppressive function via cell-cell contacts | \n91 | \n
\n | \n | ♦ Excess production of soluble factors | \n\n |
\n | \n | ✓ IL-10 | \n91 | \n
\n | \n | ✕ Enhanced suppressive function | \n89 | \n
\n | \n | ✕ Phosphorylation of STAT3 with over-expression of Bcl-2 causing resistance against asbestos-induced apoptosis | \n\n |
\n | \n | ✓ TGFβ | \n91 | \n
\n | \n | ✕ Enhanced suppressive function | \n90 | \n
\n | \n | ✕ Increased phosphorylation of p38 and SMAD3 causing resistance against TGFβ-induced growth inhibition | \n\n |
Immunological risks caused by asbestos fibers.
CXCR3, CXC chemokine receptor 3; HD, healthy donor; IFN, interferon; IL, interleukin; MLR, mixed lymphocyte reaction; MM, malignant mesothelioma; NK, natural killer; PP, pleural plaque; TGF, transforming growth factor; SMAD, vertebrate homologues of
Regarding NK cells, cytotoxicity was reduced in peripheral NK cells from pleural plaque (PP) and MM, in NK cells from HD cultured in vitro with asbestos fiber, and in a human NK cell line continuously exposed to asbestos [82]. Additionally, the expression of various NK cell activating receptors, such as NKG2D, 2B4, and NKp46, was reduced in a human NK cell line cultured continuously with asbestos, in freshly isolated NK cells from HD cultured in vitro with asbestos, and in fresh NK cells from PP and MM [82, 83]. Among these receptors, NKp46 was thought to be an important marker for impaired function of NK cells exposed to asbestos. Moreover, reduced cytotoxicity in NK cells exposed to asbestos was accompanied with reduced phosphorylation of extracellularly regulated kinases (ERK) 1 and 2 and reduced degranulation of perforin and granzyme B, which are the killing small molecules secreted from NK cells [82, 83].
\nOther types of cytokilling immune cells, CTLs, are also involved and have their functional and cellular properties altered by asbestos exposure. From in vitro analyses using peripheral CTLs in a mixed lymphocyte reaction (MLR), it was found that differentiation and proliferation of CD8+ naïve T cells were disturbed by the presence of cocultured asbestos fibers with decreased expression of killing small molecules, such as granzyme B and interferon γ (IFNγ) [84]. Moreover, alteration of killing molecules, as well as the phenotype of CD8+ cells, was manifested by CD45RA as the marker of effector/memory T cells. Freshly isolated CD8+ cells derived from asbestos-exposed patients, such as PP and MM, showed a higher predominance of CD45RA-negative cells compared with HD [85]. However, the cytokilling activity differed between isolated and in vitro
These findings indicated that asbestos exposure caused dysfunction of CTLs, while specific cell functions differed depending on disease status, for example, PP patients do not carry any malignant tumors, whereas MM patients suffer from mesothelioma. However, the impact of asbestos fibers on CTLs is considered to involve a reduction of tumor immunity, as we showed in NK cells mentioned above [84, 85].
\nAsbestos fibers are also known to modify Th1 cells. We developed continuously exposed sublines using a cell line model. The cDNA microarray data were examined of the original cell line, which has had no contact with asbestos fibers, and six independently established sublines, which were continuously exposed to asbestos fibers for more than 8 months using an asbestos concentration that did not induce apoptosis in more than half of the cells by transient exposure. The microarray showed a decrease in IFNγ and related molecules, such as IFN regulatory factor 9 (IRF9) and IFN-stimulating gene factor-3 (ISGF3), in addition to a decrease in CXC chemokine receptor 3 (CXCR3), which is regulated by IRF9 [86].
\nCXCR3 is important in antitumor immunity to summon IFNγ-positive tumor antigen recognizing Th1 cells to the tumor. Thus, the asbestos-induced reduction of CXCR3 and IFNγ seems to cause a reduction of antitumor immunity in asbestos-exposed patients. As we assumed, examination of freshly isolated CD4+ cells from HD stimulated in vitro and cocultured with asbestos fibers as well as peripheral CD4+ cells from PP and MM revealed a decrease in the cell surface expression of CXCR3 in addition to a decrease in the number of intracellular IFNγ-positive cells [87].
\nTaken together, one of the immunological risks resulting from asbestos exposure concerns a reduction of Th1-type T cell–derived antitumor immunity.
\nTreg cells are important in antitumor immunity. If the function and number of Treg cells are enhanced, immune cells responding to tumor antigen show suppressed function, which causes a reduction of antitumor immunity [75, 76].
\nOur cell line model continuously exposed to asbestos fibers using MT-2, a human T-lymphotropic virus type 1, which causes adult T cell leukemia/lymphoma, showed excess production of transforming growth factor (TGF) β and IL-10, typical soluble factors examined to reveal the function of Treg cells [88, 89]. Overproduction of IL-10 is regulated by the Src-family receptor and is used by the IL-10 receptor via autocrine mechanisms, which then causes activation of the signal transducer and activator of transcription 3 (STAT 3) and upregulation of antiapoptotic molecule Bcl-2 located downstream of STAT3 [88]. Continuously exposed sublines acquire resistance to apoptosis induced via transient exposure to asbestos [88]. Furthermore, overproduction of TGFβ induces resistance to TGFβ-induced growth inhibition in continuously exposed sublines with phosphorylation of p38, one of the signaling molecules in the mitogen-activated protein kinase (MAPK) signaling pathway, as well as phosphorylation of SMAD3 [SMAD; vertebrate homologues of
In addition to the two aforementioned typical soluble factors, continuous exposure of MT-2 sublines to asbestos resulted in markedly higher suppressive activity when mixed with cultures of CD4+ responder cells activated with anti-CD3 antibody and autologous peripheral blood monocyte-derived dendritic cells compared with the original MT-2 cell line, which has had no contact with asbestos [90].
\nTaken together, exposure to asbestos results in enhanced Treg function, which is manifested by a reduction of antitumor immunity [11, 12, 15, 16, 80, 81].
\nAs mentioned above and shown in Table 2, all of the examined effects of asbestos on NK cells, CTLs, Th1, and Treg cells indicate that asbestos exposure can cause a reduction of antitumor immunity. These findings are considerable and the risks associated with asbestos exposure may be used as early detection markers for the occurrence of asbestos-induced malignancies. Additionally, the ability to mitigate the observed reduction of antitumor immunity through the use of chemopreventive substances derived from foods or plants may be an important strategy in the treatment of high-risk groups exposed to asbestos, such as residents who have a history of living near factories handling asbestos and workers in the building demolition and rubble processing fields.
\nRisks associated with exposure to fibers, such as asbestos, and particulates, such as silica, were discussed based on our experimental findings and analyzed using cell lines, freshly isolated peripheral immune cells from HD, as well as patients exposed to silica particles, exposed to asbestos fibers, and patients with silicosis, PP, and MM. The immunological risks manifested in different directions, in that silica caused dysregulation of autoimmunity, whereas asbestos induced a reduction of antitumor immunity. Both cellular and molecular alterations contributed to the complications of silica exposure, the occurrence of autoimmune diseases and asbestos exposure, and the development of malignant tumors.
\nThese risks may be detected using findings described in this chapter, and early detection of these risks may assist workers, as well as other exposed populations, in avoiding further exposure and therefore prevent the onset of various pathological states caused by exposure to fibrous and particulate substances. Recently, although exposure to silica and asbestos has been reduced through the improvement of work-related environments as well as banning the use of asbestos, new substances, such as nanomaterials, which are widely used in the industrial fields, are now feared to cause health risks. It should be reiterated that risks, and particularly immunological ones which hitherto have not received a great deal of attention, caused by classical types of particulate and fibrous substances, such as silica and asbestos, require continued and greater consideration in an effort to further prevent the health impairment caused by environmental substances.
\nThe authors express their gratitude to the former Professor of our Department, Prof. Ayako Ueki, MD, PhD, as well as former members Drs. Akiko Tomokuni-Takata, Fuminori Hyodoh, Takaaki Aikoh, and Yasuhiko Kawakami for their excellent achievement in analyzing the risks of particulate and fibrous substances. Additionally, we thank Ms. Minako Katoh, Naomi Miyahara, Satomi Hatada, Keiko Yamashita, Keiko Kimura, Tomoko Sueishi, Misao Kuroki, and Haruko Sakaguchi for their technical assistance.
\nComputed tomography (CT) is a diagnostic tool that uses X-rays to visualize anatomical structures of the body with a good resolution [1]. It allows the identification of abnormalities related to a pathology. It has proven itself particularly in the exploration of lung parenchyma where it has a high sensitivity in the detection of neoplastic and infectious diseases [2]. Knowing that its realization lasts only about ten seconds and that the results can be immediately available, the CT scan is a tool of choice in case of high influx of symptomatic patients and requiring triage [3]. Since the occurrence of the COVID-19 pandemic, whose main symptoms are respiratory with lung parenchymal lesions responsible for a desaturation that can be rapidly fatal, CT has taken a place of choice in the management of both suspected and confirmed cases. This is due to the fact that the reference diagnostic tool, RT-PCR on nasopharyngeal swabs, has a low sensitivity despite a good specificity [4]. Moreover, this PCR test gives results delayed by one to several days, which does not facilitate the management of patients in emergency. Thus, CT is positioned both as an emergency triage tool and as a prognostic tool to assess the extent of lung parenchymal lesions while identifying other associated lesions or other complications such as pulmonary embolism [3, 5].
A thoracic CT scan is performed on a patient in dorsal recumbency, with the hands placed behind the head. The patient must maintain a deep inspiration during the acquisition, which lasts about ten seconds. This acquisition must cover the whole thorax from the apex to the costo-diaphragmatic cul-de-sac. Ideally, for patients with COVID or suspected COVID, it is better to perform the examination with a dose optimization protocol (low-dose) [6]. This will reduce the cumulative irradiation dose, when we know that these patients may have to undergo several CT scans depending on their evolution.
However, the examination should be performed with injection of iodinated contrast medium, in thoracic angio-CT, when there is a clinical suspicion of pulmonary embolism [7].
The CT scan essentially allows the identification of the elementary lesions attributable to COVID-19, which are ground-glass opacity, crazy-paving and non-systematized condensation [8, 9].
The ground-glass opacity, which corresponds to an opacity of the lung parenchyma that does not erase the pulmonary vessels (Figure 1A and B), is the most frequent sign found in COVID-19 between 88% and 94% [9, 10].
Chest CT in lung window, axial section (A) and sagittal reconstruction (B) typical form of COVID-19 pulmonary lesions with bilateral areas of ground glass opacities limited to the sub pleura and predominantly at the lung bases.
However, ground glass opacity is a non-specific sign of COVID-19 and therefore it is above all its distribution on the lung parenchyma that is decisive for the diagnosis. In the typical form, this distribution is in bilateral sub pleural patches, predominantly in the posterior and basal regions (Figure 1A and B) [11]. However, there are less typical forms with a central, unilateral, predominantly apical or nodular distribution [10].
Crazy-paving, which corresponds to ground-glass opacity associated with thickening of the lobular septa (Figure 2A and B), is usually found in the evolution of ground-glass lesions [12].
Chest CT in lung window, axial sections (A and B). Thickening of the septa on a ground glass background giving the appearance of crazy-paving.
The same is true for non-systematic condensation which can occur by transformation of the initial lesions [12]. This condensation will appear as an increase in density of the lung parenchyma but unlike the ground-glass opacity, it will erase the pulmonary vessels (Figure 3A and B).
Chest CT in lung window, axial section (A) and coronal reconstruction (B) bilateral patches of non-systematic sub pleural condensation, corresponding to an evolution of ground glass lesions in relation to COVID-19.
As important as it is to know how to recognize CT signs compatible with COVID-19 infection, it is equally important to know how to differentiate it from other pathologies that require a different management and that can be life-threatening emergencies.
These differential diagnoses are first and foremost the other causes of ground-glass opacity. This is a long list covering several diffuse interstitial lung disease, acute pulmonary edema and alveolar hemorrhage among others [13]. Other causes of crazy-paving and condensation will also be a differential diagnosis, including several diffuse interstitial lung diseases, pneumonia, acute pulmonary edema, bronchioloalveolar carcinoma among others [14].
On imaging, it is important to differentiate the lesions of covid-19 with those of acute pulmonary edema and alveolar hemorrhage which are high emergencies and require specific treatment. What helps in this distinction is essentially the distribution of the lesions which are typically sub pleural in COVID-19 and on the contrary spares the sub pleural regions in alveolar hemorrhage and acute pulmonary edema (Figure 4A and B) [15].
Chest CT in lung window, axial section (A) and coronal reconstruction (B) bilateral areas of condensation and ground glass opacities, confluent, centrally distributed, clearly sparing the sub pleural regions. This gives the butterfly wing appearance which is in favor of pulmonary edema and rules out the suspicion of Covid-19 in the patient.
However, in each case, this differential diagnosis must consider the clinical elements, the evolution and the biological data.
The most important factor of severity is the degree of extent of the lesions on the lung parenchyma. A visual grading of these lung lesions has been proposed by the Society of Thoracic Imaging (STI) in five stages ranging from less than 10% involvement (minimal) to more than 75% involvement (critical) [16]. This degree of lung involvement is important to specify because it constitutes a prognostic element.
Other elements of severity are the existence of sequelae or evolving pulmonary lesions (pulmonary emphysema, sequelae of granulomatosis, active tuberculosis infection, among others).
Among the complications, the most feared and expected is pulmonary embolism [17]. The risk of embolism is high because of the significant inflammatory response during COVID-19, which makes it a highly thrombogenic pathology [18]. The search for a clinically suspected pulmonary embolism is the main indication for thoracic angio-CT in COVID-19 (Figure 5A and B) [7].
Thoracic CT angiography in mediastinal window with coronal (A) and sagittal (B) reconstruction pulmonary embolism with endoluminal defect at the level of a left posterobasal segmental pulmonary artery branch (red arrows).
Other complications are pneumothorax and pneumomediastinum, which may occur spontaneously or as a result of mechanical ventilation [19].
Bacterial reinfection can also occur in COVID-19 pneumonia. In this case, there is a systematized condensation at a lobe or a segment, unlike the condensations related to COVID which follow the distribution of ground glass lesions, remaining sub pleural and not systematized [20].
All these elements of severity and complications influence the prognosis of the patient, which makes thoracic CT an important prognostic tool.
The evolution of COVID-19 lung disease can be towards a regression of the lesions with possible restitution ad integrum if an adequate treatment has been initiated in time. However, it should be kept in mind that regression of lesions on CT is lagging behind clinical improvement [21]. Therefore, it is important to avoid too frequent CT scans, which would be a source of unnecessary irradiation.
The evolution may also take the form of fibrosing parenchymal sequelae [21].
Furthermore, it should be borne in mind that pulmonary embolism may occur during the evolution of the disease.
COVID 19 is a systemic disease, although thoracic and particularly pulmonary involvement is prominent. CT can be an important tool for some of these extra thoracic conditions [22].
Among the extra thoracic uses of CT, we note in particular the angio-CT of the limbs in cases of suspected arterial thrombosis of the limbs during COVID-19 (Figure 6A and B).
Angio-CT of the lower limbs in a COVID patient with ischemia of the left lower limb. (A) Angiographic reconstruction showing the thrombosis of the superficial femoral artery from its origin (red arrow) to its lower third with revascularization by collaterals from the deep femoral artery. (B) VRT reconstruction showing the thrombosis extending over a height of 18.6 cm.
CT has the advantage of having good spatial resolution but also availability and speed of image acquisition, which only takes about ten seconds. The reading of the images is also fast and quite easy compared to other imaging methods.
In addition, CT has good sensitivity in the detection of COVID-19 lung lesions, when compared with the reference diagnostic tool that is RT-PCR [23].
Another advantage is its contribution to the prognosis of patients by providing an overview of the lung volume affected by the lesions.
The main disadvantage of CT is the irradiation, which justifies the use of dose optimization (low-dose CT) to minimize the consequences that could result from it [24].
The other disadvantage is the low specificity of lesions on CT, compared to RT-PCR. This should be considered to avoid overdiagnosis of COVID-19 on CT [23].
The mobile CT allows to palliate the need for specialized transport of patients with or suspected of having COVID-19 for whom a CT scan is necessary. This transport may require particularly important logistics, especially for patients in intensive care [25]. For these patients, it is often easier and safer to bring a mobile device to their bedside than to move them to the imaging department, hence the importance of mobile CT in their management. And this mobile CT provides good quality images with a sensitivity that remains superior to the PCR test [25, 26].
Postmortem CT has positioned itself as an alternative to autopsy in deceased COVID-19 patients or in those suspected of having COVID-19. In these patients there is a high risk of contamination during the autopsy and this examination requires protective equipment that is not always available [27]. The thanatoradiological semiology of COVID-19 on CT is identical to that of living patients.
Artificial intelligence is increasingly used as a means of fluidity and ease in several fields using technology, imaging and particularly CT is no exception. In the case of Covid-19, artificial intelligence associated with CT helps to make the diagnosis more accurate and also provides greater precision on the lung volume affected by the lesions [28].
This chapter has demonstrated the great usefulness of CT-scan in the fight against coronavirus pandemic, due to its rapid image acquisition, its immediate availability of results, its good spatial resolution and especially its high sensitivity in the detection of COVID-19 lesions. These assets are reinforced by mobile CT facilitating access to quality imaging in intensive care patients and the coupling with artificial intelligence tools providing greater diagnostic accuracy and assessment of lesion extent.
All of this should give CT a primary place in the response to future lung-tropic pandemics, such as the coronavirus.
The authors declare no conflict of interest.
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The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
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\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
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\n\nLast updated: 2020-11-27
\n\n\n\n
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Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"302145",title:"Dr.",name:"Felix",middleName:null,surname:"Bongomin",slug:"felix-bongomin",fullName:"Felix Bongomin",profilePictureURL:"https://mts.intechopen.com/storage/users/302145/images/system/302145.jpg",institutionString:null,institution:{name:"Gulu University",institutionURL:null,country:{name:"Uganda"}}},{id:"45803",title:"Ph.D.",name:"Payam",middleName:null,surname:"Behzadi",slug:"payam-behzadi",fullName:"Payam Behzadi",profilePictureURL:"https://mts.intechopen.com/storage/users/45803/images/system/45803.jpg",institutionString:"Islamic Azad University, Tehran",institution:{name:"Islamic Azad University, Tehran",institutionURL:null,country:{name:"Iran"}}}]},onlineFirstChapters:{paginationCount:14,paginationItems:[{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"80954",title:"Ion Channels and Neurodegenerative Disease Aging Related",doi:"10.5772/intechopen.103074",signatures:"Marika Cordaro, Salvatore Cuzzocrea and Rosanna Di Paola",slug:"ion-channels-and-neurodegenerative-disease-aging-related",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Ion Channels - From Basic Properties to Medical Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/10838.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"81647",title:"Diabetes and Epigenetics",doi:"10.5772/intechopen.104653",signatures:"Rasha A. 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