scholarly journals The immune responses to bacterial antigens encountered in vivo at mucosal surfaces

2000 ◽  
Vol 355 (1397) ◽  
pp. 705-712 ◽  
Author(s):  
Gordon Dougan ◽  
Marjan Ghaem–Maghami ◽  
Derek Pickard ◽  
Gad Frankel ◽  
Gill Douce ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Mucosal Surfaces ◽  
Bacterial Antigens ◽  
Mucosal Vaccines ◽  
Derivatives Of ◽  
The Way

Mammals have evolved a sophisticated immune system for handling antigens encountered at their mucosal surfaces. The way in which mucosally delivered antigens are handled influences our ability to design effective mucosal vaccines. Live attenuated derivatives of pathogens are one route towards the development of mucosal vaccines. However, some molecules, described as mucosal immunogens, are inherently immunogenic at mucosal surfaces. Studies on mucosal immunogens may facilitate the identification of common characteristics that contribute to mucosal immunogenicity and aid the development of novel, non–living mucosal vaccines and immunostimulators.

THE IMMUNE RESPONSES TO BACTERIAL ANTIGENS ENCOUNTERED IN VIVO AT MUCOSAL SURFACES

2001 ◽  
Author(s):  
GORDON DOUGAN ◽  
MARJAN GHAEM-MAGHAMI ◽  
DEREK PICKARD ◽  
GAD FRANKEL ◽  
GILL DOUCE ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mucosal Surfaces ◽  
Bacterial Antigens

Cell-Penetrating Peptide-Mediated Nanovaccine Delivery

2021 ◽  
Vol 22 ◽  
Author(s):  
Jizong Jiang
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cell Penetrating Peptide ◽  
Antigen Delivery ◽  
Efficient Manner ◽  
Antigen Uptake ◽  
Cell Penetrating ◽  
The Stability ◽  
Antigen Presenting

Abstract: Vaccination with small antigens, such as proteins, peptides, or nucleic acids, is used to activate the immune system and trigger the protective immune responses against a pathogen. Currently, nanovaccines are undergoing development instead of conventional vaccines. The size of nanovaccines is in the range of 10–500 nm, which enables them to be readily taken up by cells and exhibit improved safety profiles. However, low-level immune responses, as the removal of redundant pathogens, trigger counter-effective activation of the immune system invalidly and present a challenging obstacle to antigen recognition and its uptake via antigen-presenting cells (APCs). In addition, toxicity can be substantial. To overcome these problems, a variety of cell-penetrating peptide (CPP)-mediated vaccine delivery systems based on nanotechnology have been proposed, most of which are designed to improve the stability of antigens in vivo and their delivery into immune cells. CPPs are particularly attractive components of antigen delivery. Thus, the unique translocation property of CPPs ensures that they remain an attractive carrier with the capacity to deliver cargo in an efficient manner for the application of drugs, gene transfer, protein, and DNA/RNA vaccination delivery. CPP-mediated nanovaccines can enhance antigen uptake, processing, and presentation by APCs, which are the fundamental steps in initiating an immune response. This review describes the different types of CPP-based nanovaccines delivery strategies.

scholarly journals Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus

2010 ◽  
Vol 84 (24) ◽  
pp. 12703-12712 ◽  
Author(s):  
Hiroyuki Kayamuro ◽  
Yasuo Yoshioka ◽  
Yasuhiro Abe ◽  
Shuhei Arita ◽  
Kazufumi Katayama ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Interleukin 1 ◽  
Influenza Virus Infection ◽  
Mucosal Vaccine ◽  
Vaccine Adjuvants ◽  
Mucosal Surfaces ◽  
Mucosal Vaccines ◽  
Etiological Agents ◽  
Family Cytokine

ABSTRACT A safe and potent adjuvant is needed for development of mucosal vaccines against etiological agents, such as influenza virus, that enter the host at mucosal surfaces. Cytokines are potential adjuvants for mucosal vaccines because they can enhance primary and memory immune responses enough to protect against some infectious agents. For this study, we tested 26 interleukin (IL) cytokines as mucosal vaccine adjuvants and compared their abilities to induce antigen (Ag)-specific immune responses against influenza virus. In mice intranasally immunized with recombinant influenza virus hemagglutinin (rHA) plus one of the IL cytokines, IL-1 family cytokines (i.e., IL-1α, IL-1β, IL-18, and IL-33) were found to increase Ag-specific immunoglobulin G (IgG) in plasma and IgA in mucosal secretions compared to those after immunization with rHA alone. In addition, high levels of both Th1- and Th2-type cytokines were observed in mice immunized with rHA plus an IL-1 family cytokine. Furthermore, mice intranasally immunized with rHA plus an IL-1 family cytokine had significant protection against a lethal influenza virus infection. Interestingly, the adjuvant effects of IL-18 and IL-33 were significantly decreased in mast cell-deficient W/W v mice, indicating that mast cells have an important role in induction of Ag-specific mucosal immune responses induced by IL-1 family cytokines. In summary, our results demonstrate that IL-1 family cytokines are potential mucosal vaccine adjuvants and can induce Ag-specific immune responses for protection against pathogens like influenza virus.

scholarly journals T-bet fate mapping identifies a novel ILC1-ILC2 subset in vivo

2020 ◽  
Author(s):  
J-H Schroeder ◽  
N Garrido-Mesa ◽  
T Zabinski ◽  
AL Gallagher ◽  
L Campbell ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Fate Mapping ◽  
Functional Roles ◽  
Mucosal Surfaces ◽  
Group 2

ABSTRACTInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Various subsets exist resembling T cell lineages defined by the expression of specific transcription factors. Thus, T-bet is expressed in ILC1 and Th1 cells. In order to further understand the functional roles of T-bet in ILC, we generated a fate-mapping mouse model that permanently marks cells and their progeny that are expressing, or have ever expressed T-bet. Here we have identified and characterised a novel ILC with characteristics of ILC1 and ILC2 that are “fate-mapped” for T-bet expression and arise early in neonatal life prior to establishment of a mature microbiome. These ILC1-ILC2 cells are critically dependent on T-bet and are able to express type 1 and type 2 cytokines at steady state, but not in the context of inflammation. These findings refine our understanding of ILC lineage regulation and stability and have important implications for the understanding of ILC biology at mucosal surfaces.SUMMARYInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Three distinct ILC groups have been described according to expression of subset defining transcription factors and other markers. In this study we characterize a novel ILC subset with characteristics of group 1 and group 2 ILC in vivo.

scholarly journals Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Julio Aliberti
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Food Allergies ◽  
Commensal Flora ◽  
Inflammatory Conditions ◽  
Mucosal Surfaces ◽  
Dendritic Cell Population ◽  
Proinflammatory Responses ◽  
Environmental Antigens

Dendritic cells present in the digestive tract are constantly exposed to environmental antigens, commensal flora, and invading pathogens. Under steady-state conditions, these cells have high tolerogenic potential, triggering differentiation of regulatory T cells to protect the host from unwanted proinflammatory immune responses to innocuous antigens or commensals. On the other hand, these cells must discriminate between commensal flora and invading pathogens and mount powerful immune response against pathogens. A potential result of unbalanced tolerogenic versus proinflammatory responses mediated by dendritic cells is associated with chronic inflammatory conditions, such as Crohn’s disease, ulcerative colitis, food allergies, and celiac disease. Herein, we review the dendritic cell population involved in mediating tolerance and immunity in mucosal surfaces, the progress in unveiling their development in vivo, and factors that can influence their functions.

scholarly journals One by One – Insights into Complex Immune Responses through Functional Single-cell Analysis

2020 ◽  
Vol 74 (9) ◽  
pp. 716-723
Author(s):  
Klaus Eyer
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Ex Vivo ◽  
Dynamic Heterogeneity ◽  
Analytical Strategies ◽  
High Dynamic ◽  
The Individual

Immune responses are highly dynamic and complex. The successful completion thereof involves and needs many different cells from the immune system, and requires their specific interactions and functions. Individual cells are the functional units within any immune response, and their varying frequencies and degrees of activity shape and define the response. The state, activation and ultimately functionality of immune cells displays high dynamic heterogeneity. Hence, there is a need for quantitative high-throughput systems that allow for a dynamic and functional single-cell phenotyping, linking function to the individual cells. In this regard, my research group focuses on developing and applying technologies and analytical strategies that allow us to measure, describe and exploit functionality within the immune system, resolved down to the individual, primary cell, to study novel and unique research questions. While doing ex vivo measurements, we are aiming to understand the functionalities of the extracted cells in vivo , within the context of our applied disturbance – vaccination, infection or malignant transformation.

scholarly journals Positive and Negative Regulation of Cellular Immune Responses in Physiologic Conditions and Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
S. Viganò ◽  
M. Perreau ◽  
G. Pantaleo ◽  
A. Harari
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Immune Responses ◽  
Viral Infections ◽  
Therapeutic Interventions ◽  
Cellular Immune

The immune system has evolved to allow robust responses against pathogens while avoiding autoimmunity. This is notably enabled by stimulatory and inhibitory signals which contribute to the regulation of immune responses. In the presence of a pathogen, a specific and effective immune response must be induced and this leads to antigen-specific T-cell proliferation, cytokines production, and induction of T-cell differentiation toward an effector phenotype. After clearance or control of the pathogen, the effector immune response must be terminated in order to avoid tissue damage and chronic inflammation and this process involves coinhibitory molecules. When the immune system fails to eliminate or control the pathogen, continuous stimulation of T cells prevents the full contraction and leads to the functional exhaustion of effector T cells. Several evidences bothin vitroandin vivosuggest that this anergic state can be reverted by blocking the interactions between coinhibitory molecules and their ligands. The potential to revert exhausted or inactivated T-cell responses following selective blocking of their function made these markers interesting targets for therapeutic interventions in patients with persistent viral infections or cancer.

scholarly journals Transcriptomic Analysis of the Host Response to Giardia duodenalis Infection Reveals Redundant Mechanisms for Parasite Control

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Ernest A. Tako ◽  
Maryam F. Hassimi ◽  
Erqiu Li ◽  
Steven M. Singer
Keyword(s):  
Nitric Oxide ◽  
Mast Cell ◽  
Immune System ◽  
Immune Responses ◽  
Diarrheal Disease ◽  
Giardia Duodenalis ◽  
Parasite Control ◽  
Content Type ◽  
Deficient Mice

ABSTRACTThe immune system has numerous mechanisms that it can use to combat pathogens and eliminate infections. Nevertheless, studies of immune responses often focus on single pathways required for protective responses. We applied microarray analysis of RNA in order to investigate the types of immune responses produced against infection with the intestinal pathogenGiardia duodenalis. Infection withG. duodenalisis one of the most common causes of diarrheal disease in the world. While several potential antiparasitic effector mechanisms, including complement lysis, nitric oxide (NO), and α-defensin peptides, have been shown to inhibit parasite growth or killGiardia in vitro, studiesin vivohave thus far shown clear roles only for antibody and mast cell responses in parasite control. A total of 96 transcripts were identified as being upregulated or repressed more than 2-fold in the small intestine 10 days following infection. Microarray data were validated using quantitative PCR. The most abundant category of transcripts was antibody genes, while the most highly induced transcripts were all mast cell proteases. Among the other induced transcripts was matrix metalloprotease 7 (Mmp7), the protease responsible for production of mature α-defensins in mice. While infections in Mmp7-deficient mice showed only a small increase in parasite numbers, combined genetic deletion of Mmp7 and inducible nitric oxide synthase (iNOS, Nos2) or pharmacological blockade of iNOS in Mmp7-deficient mice resulted in significant increases in parasite loads following infection. Thus, α-defensins and NO are redundant mechanisms for control ofGiardiainfectionsin vivo.IMPORTANCEThe immune system has multiple weapons which it uses to help control infections. Many infections result in activation of several of these response mechanisms, but it is not always clear which responses actually contribute to control of the pathogen and which are bystander effects. This study used the intestinal parasiteGiardia duodenalisto examine the redundancy in immune responses during infections in mice. Our results showed that at least four distinct mechanisms are activated following infections. Furthermore, by blocking two pathways at the same time, we showed that both mechanisms contribute to control of the infection, whereas blocking single responses showed no or minimal effect in these cases.

scholarly journals MicroRNAs of Epstein-Barr Virus Attenuate T-Cell-Mediated Immune ControlIn Vivo

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Anita Murer ◽  
Julia Rühl ◽  
Andrea Zbinden ◽  
Riccarda Capaul ◽  
Wolfgang Hammerschmidt ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Immune Responses ◽  
Epstein Barr Virus ◽  
Tumor Formation ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACTThe human persistent and oncogenic Epstein-Barr virus (EBV) was one of the first viruses that were described to express viral microRNAs (miRNAs). These have been proposed to modulate many host and viral functions, but their predominant rolein vivohas remained unclear. We compared recombinant EBVs expressing or lacking miRNAs duringin vivoinfection of mice with reconstituted human immune system components and found that miRNA-deficient EBV replicates to lower viral titers with decreased frequencies of proliferating EBV-infected B cells. In response, activated cytotoxic EBV-specific T cells expand to lower frequencies than during infection with miRNA-expressing EBV. However, when we depleted CD8+T cells the miRNA-deficient virus reached similar viral loads as wild-type EBV, increasing by more than 200-fold in the spleens of infected animals. Furthermore, CD8+T cell depletion resulted in lymphoma formation in the majority of animals after miRNA-deficient EBV infection, while no tumors emerged when CD8+T cells were present. Thus, miRNAs mainly serve the purpose of immune evasion from T cellsin vivoand could become a therapeutic target to render EBV-associated malignancies more immunogenic.IMPORTANCEEpstein-Barr virus (EBV) infects the majority of the human population and usually persists asymptomatically within its host. Nevertheless, EBV is the causative agent for infectious mononucleosis (IM) and for lymphoproliferative disorders, including Burkitt and Hodgkin lymphomas. The immune system of the infected host is thought to prevent tumor formation in healthy virus carriers. EBV was one of the first viruses described to express miRNAs, and many host and viral targets were identified for thesein vitro. However, their role during EBV infectionin vivoremained unclear. This work is the first to describe that EBV miRNAs mainly increase viremia and virus-associated lymphomas through dampening antigen recognition by adaptive immune responses in mice with reconstituted immune responses. Currently, there is no prophylactic or therapeutic treatment to restrict IM or EBV-associated malignancies; thus, targeting EBV miRNAs could promote immune responses and limit EBV-associated pathologies.

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