Current Immunology Reviews最新文献

{"title":"Meet Our Editorial Board Member","authors":"Shao-Cong Sun","doi":"10.2174/157339551501190307091314","DOIUrl":"https://doi.org/10.2174/157339551501190307091314","url":null,"abstract":"","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157339551501190307091314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49577572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Monoclonal Antibodies to Prevent the Sexual Transmission of Human Immunodeficiency Virus Type 1","authors":"Deborah J Anderson, J. Politch, G. Vaca, K. Kadasia, K. Whaley","doi":"10.2174/1573395514666180605091240","DOIUrl":"https://doi.org/10.2174/1573395514666180605091240","url":null,"abstract":"\u0000\u0000<P>Passive immunization has been used since the late 1800’s to prevent and treat human\u0000infectious diseases. Administration of animal immune sera and human immunoglobulin has given\u0000way to the use of monoclonal antibodies (mAbs) for passive immunization, and highly potent broadly\u0000neutralizing anti-HIV antibodies (bNAbs) are now being considered for HIV therapy and prophylaxis.\u0000Recent studies have shown that systemic and topical administration of bNAbs can effectively inhibit\u0000HIV/SHIV mucosal transmission in macaques and in humanized mice, and selected bNAbs are\u0000currently being tested in clinical trials for safety and efficacy in humans.\u0000\u0000\u0000\u0000\u0000In this review, we outline strategies for the selection, engineering and manufacture of human bNAbs\u0000to prevent the sexual transmission of HIV, describe the proof-of-concept animal studies that have\u0000demonstrated mAb-mediated protection against mucosal HIV transmission, and review clinical trials\u0000currently underway to test the safety and efficacy of mAb-based HIV prevention in humans.\u0000","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43008021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Sex Hormones in Regulating Innate Immune Protection against HIV in the Human Female Reproductive Tract","authors":"Mickey V. Patel, M. Rodriguez-Garcia, C. Wira","doi":"10.2174/1573395514666180605082507","DOIUrl":"https://doi.org/10.2174/1573395514666180605082507","url":null,"abstract":"\u0000\u0000Immune protection in the female reproductive tract (FRT) has evolved to meet the\u0000challenges of sexually transmitted bacterial and viral pathogens, allogeneic spermatozoa, and an\u0000immunologically distinct semi-allogeneic fetus. Throughout the FRT, the innate immune system is\u0000essential for the recognition and initial response to incoming pathogens. Key mediators of innate\u0000immune protection examined in this review include epithelial cells, stromal fibroblasts, macrophages,\u0000DC, and neutrophils from the Fallopian tubes, uterus, cervix and vagina. These innate immune cells\u0000respond to pathogens resulting in the secretion of cytokines, chemokines, antimicrobials, and\u0000production of intracellular proteins that protect, activate and recruit both innate and adaptive immune\u0000cells. Human immunodeficiency virus (HIV) infection can occur throughout the FRT, including the\u0000ovary, and is modulated by multiple factors including age of the individual, epithelial barrier\u0000integrity, composition of the vaginal microbiome, and hormonal status. Alterations in immune\u0000function due to hormonal changes that optimize conditions for successful fertilization create a\u0000hypothesized “window of vulnerability” that lasts from ovulation into the secretory stage of the\u0000menstrual cycle. The goal of this review is to summarize the multiple levels of protection against HIV\u0000infection in the FRT and thereby providing a foundation for the design of vaccines for protection\u0000against sexually-transmitted infections (STI) including HIV.\u0000","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47813912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virologic Aspects of Mucosal Transmission","authors":"Z. Ende, Martin J. Deymier, E. Hunter","doi":"10.2174/1573395514666180626151737","DOIUrl":"https://doi.org/10.2174/1573395514666180626151737","url":null,"abstract":"The transmission of HIV is generally inefficient. Despite the development of a diverse viral quasispecies in a chronically infected individual, a severe genetic bottleneck is observed during transmission, leading to only one or a few genetic variants establishing infection. This genetic bottleneck is the result of both stochastic events and selection pressures, such that viruses with specific traits are favored during transmission. This chapter discusses current models of HIV mucosal transmission, evidence for selection of specific viral traits during this process, and the biological characterization of transmitted founder viruses based on monkey models and human cohorts. The impact of transmitted viral phenotypes on disease progression is also described. Understanding in greater depth the key viral features required for transmission will be essential to the development of effective interventions for HIV prevention.","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1573395514666180626151737","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41945178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV-1/SIV Humoral Responses in External Secretions","authors":"Jiri Mestecky and Georgia D. Tomaras","doi":"10.2174/1573395514666180528081557","DOIUrl":"https://doi.org/10.2174/1573395514666180528081557","url":null,"abstract":"The protective function of mucosal HIV-1- or SIV-specific antibodies against viral infection has stimulated extensive studies of their Ig isotype association with differences in specificity and in effector functions. In contrast to many mucosally acquired microbial infections in which the humoral responses are dominated by induction of secretory IgA (S-IgA), HIV-1/SIV infections stimulate vigorous IgG responses in sera as well as in external secretions but low IgA virus-specific antibodies although the total levels of IgA in these fluids remain unaltered. The diminished or even absent IgA responses to HIV-1/SIV and to other mucosal antigens in external secretions and their replacement with IgG is likely to influence the functionality of mucosal barriers and eliminate antiinflammatory effector functions of IgA antibodies. Furthermore, the polymeric character of S-IgA with 4-8 antigen-binding sites, exquisite resistance to proteolysis and anti-inflammatory potential are of great advantage in mucosal protection. The markedly different effector functions of mucosal antibodies of IgG and IgA isotypes must be considered in the design of HIV-1 vaccines to stimulate S-IgA responses at sites of virus entry and IgG responses in the systemic compartment.","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45443065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers of Mucosal Entry of HIV/SIV.","authors":"Ann M Carias,&nbsp;Thomas J Hope","doi":"10.2174/1573395514666180604084404","DOIUrl":"https://doi.org/10.2174/1573395514666180604084404","url":null,"abstract":"<p><p>Most new HIV infections, over 80%, occur through sexual transmission. During sexual transmission, the virus must bypass specific female and male reproductive tract anatomical barriers to encounter viable target cells. Understanding the generally efficient ability of these barrier to exclude HIV and the precise mechanisms of HIV translocation beyond these genital barriers is essential for vaccine and novel therapeutic development. In this review, we explore the mucosal, barriers of cervico-vaginal and penile tissues that comprise the female and male reproductive tracts. The unique cellular assemblies f the squamous and columnar epithelium are illustrate highlighting their structure and function. Each anatomical tissue offers a unique barrier to virus entry in healthy individuals. Unfortunately barrier dysfunction can lead to HIV transmission. How these diverse mucosal barriers have the potential to fail is considered, highlighting those anatomical areas that are postulated to offer a weaker barrier and are; therefore, more susceptible to viral ingress. Risk factors, such as sexually transmitted infections, microbiome dysbiosis, and high progestin environments are also associated with increased acquisition of HIV. How these states may affect the integrity of mucosal barriers leading to HIV acquisition are discussed suggesting mechanisms of transmission and revealing potential targets for intervention.</p>","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":"15 1","pages":"4-13"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919325/pdf/nihms-1061672.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37471091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV and SIV in Body Fluids: From Breast Milk to the Genitourinary Tract.","authors":"Kattayoun Kordy,&nbsp;Nicole H Tobin,&nbsp;Grace M Aldrovandi","doi":"10.2174/1573395514666180605085313","DOIUrl":"https://doi.org/10.2174/1573395514666180605085313","url":null,"abstract":"<p><p>HIV-1 is present in many secretions including oral, intestinal, genital, and breast milk. However, most people exposed to HIV-1 within these mucosal compartments do not become infected despite often frequent and repetitive exposure over prolonged periods of time. In this review, we discuss what is known about the levels of cell-free HIV RNA, cell-associated HIV DNA and cell-associated HIV RNA in external secretions. Levels of virus are usually lower than contemporaneously obtained blood, increased in settings of inflammation and infection, and decreased in response to antiretroviral therapy. Additionally, each mucosal compartment has unique innate and adaptive immune responses that affect the composition and presence of HIV-1 within each external secretion. We discuss the current state of knowledge about the types and amounts of virus present in the various excretions, touch on innate and adaptive immune responses as they affect viral levels, and highlight important areas for further study.</p>","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":"15 1","pages":"139-152"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730163/pdf/nihms-1048537.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38366913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Mucosal Humoral and Cellular Immune Responses to HIV in External Secretions and Mucosal Tissues.","authors":"Steffanie Sabbaj, Jiri Mestecky","doi":"10.2174/1573395514666180621152303","DOIUrl":"10.2174/1573395514666180621152303","url":null,"abstract":"<p><p>The mucosal immune systems of the genital and intestinal tracts as the most frequent sites of HIV-1 entry, display remarkable immunological differences from the systemic immune compartment which must be considered in the evaluation of humoral and cellular immune responses to HIV-1. Marked differences in the fluids from the genital and intestinal tracts and in plasma with respect to the Ig isotypes, their levels, molecular forms and distinct effector functions must be taken into consideration in the evaluation and interpretation of humoral immune responses. Because of the low levels and highly pronounced variation in Ig content, HIV-1-specific antibody concentrations should be always related to the levels of total Ig of a given isotype. This practice will avoid inevitable differences due to the small volumes of collected fluids and sample dilution during the collection and processing of samples from external secretions. Furthermore, appropriate controls and immunochemical assays should be used to complement and confirm results generated by ELISA, which is prone to false positivity. In the evaluation of antibody-mediated virus neutralization in external secretions, precautions and rigorous controls must be used to exclude the effect of innate humoral factors. The evaluation of cell-mediated immune responses in mucosal tissues is difficult due to the low yields of cells obtained from tissue biopsies or cytobrush scrapings. Furthermore, tissue biopsies of, for example rectal mucosa, provide information pertinent exclusively to this local site, which due to the differences in distribution of cells of different phenotypes, do not provide information generalized to the entire intestinal tract. Importantly, studies concerning the kinetics of cellular responses are difficult to perform due to the limited availability of samples or to the inability of obtaining frequent repeated tissue biopsies. For sampling the female genital tract parallel collection of menstrual and peripheral blood yields high numbers of cells that permit their detailed phenotypic and functional analyses. In contrast to tissue biopsies, this non-traumatic collection procedure, results in high cell yields and repeated monthly sampling permits extensive and parallel functional studies of kinetics and unique characteristics of HIV-1-specific cellular responses in the female genital tract and peripheral blood.</p>","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":"15 1","pages":"41-48"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731984/pdf/nihms-1050920.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38366911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucosal Immune System and HIV/SIV.","authors":"Jiri Mestecky,&nbsp;Ronald Veazey","doi":"10.2174/157339551501190307091523","DOIUrl":"https://doi.org/10.2174/157339551501190307091523","url":null,"abstract":"Current epidemiological data convincingly indicate that HIV infection is acquired predominantly by the mucosal route, analogous with the majority of infectious diseases [1]. Mucosal surfaces of the genital and intestinal tracts are the major sites of virus entry, yet major discoveries and advances in the technologies in the last decade alone have reinforced the importance of examining mucosal immune responses. The earliest and most profound alterations of the immune system occur in mucosal tissues of the intestinal tract, which constitute a crucial step in the pathogenesis of HIV [2, 3]. Furthermore, untreated HIV patients are also usually infected by opportunistic mucosal pathogens of viral, bacterial, fungal and parasitic origin. The marked quantitative and qualitative differences of the mucosal and systemic compartments of the immune system comprise the dominant mucosal site of exposure to environmental antigens; phenotypically distinct cell populations including the antigen-presenting dendritic cells, macrophages, epithelial cells, T and B lymphocytes, innate lymphoid cells, plasma cells; production and selective transport of antibodies; and unique innate factors of immunity present in mucosal tissues and secretions. In particular, HIV exploits the unique aspects of the mucosal immune system, especially its reservoir of activated CD4+ T target cells, which support viral infection, amplification, mutation, and destruction of key immunoregulatory cells involved in mucosal immunity. Loss of mucosal barrier integrity permits translocation of foreign antigens into the systemic circulation resulting in further viral replication and continual seeding of viral reservoirs [3, 4]. Furthermore, the loss of immunoregulatory T cells in mucosal tissues contributes to the lack of normal immune suppression, leading to increased levels of inflammation supportive of continued HIV replication and persistence in tissues. Finally, mucosal tissues are increasingly recognized as the major reservoir for viral persistence in patients on antiretroviral therapy, especially in the Gut-Associated Lymphoid Tissues (GALT) of the lower intestinal tract.","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":"15 1","pages":"2-3"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157339551501190307091523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38630715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric HIV-1 Acquisition and Lifelong Consequences of Infant Infection.","authors":"Cody S Nelson, Genevieve G A Fouda, Sallie R Permar","doi":"10.2174/1573395514666180531074047","DOIUrl":"10.2174/1573395514666180531074047","url":null,"abstract":"<p><p>Increased availability of antiretroviral therapy to pregnant and breastfeeding women in resource-limited areas has proven remarkably successful at reducing HIV vertical transmission rates over the past several decades. Yet, still more than 170,000 children are infected annually due to failures in therapy implementation, monitoring, and adherence. Mother-to-child transmission (MTCT) of HIV-1 can occur at one of several distinct stages of infant development - intrauterine, intrapartum, and postpartum. The heterogeneity of the maternal-fetal interface at each of these modes of transmission poses a challenge for the implementation of immune interventions to prevent all modes of HIV MTCT. However, using mother-infant human cohorts and nonhuman primate models of infant simian immunodeficiency virus (SIV) acquisition, investigators have made important observation about the biology of pediatric HIV infection and have identified unique protective immune factors for each mode of transmission. Knowledge of immune factors protective against HIV MTCT will be critical to the development of targeted immune therapies to prevent infant HIV acquisition and to bring an end to the pediatric AIDS epidemic.</p>","PeriodicalId":35403,"journal":{"name":"Current Immunology Reviews","volume":"15 1","pages":"131-138"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678020/pdf/nihms-1046553.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38630718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}