scholarly journals Acellular Pertussis Vaccines and Pertussis Resurgence: Revise or Replace?

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Clara Maria Ausiello ◽  
Antonio Cassone
Keyword(s):  
Immune Responses ◽  
Whooping Cough ◽  
Experimental Models ◽  
Adaptive Immune Responses ◽  
Content Type ◽  
Antigenic Composition ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Antibody Levels ◽  
Stimulation Of

ABSTRACTThe resurgence of pertussis (whooping cough) in countries with high vaccination coverage is alarming and invites reconsideration of the use of current acellular pertussis (aP) vaccines, which have largely replaced the old, reactogenic, whole-cell pertussis (wP) vaccine. Some drawbacks of these vaccines in terms of limited antigenic composition and early waning of antibody levels could be anticipated by the results of in-trial or postlicensure human investigations of B- and T-cell responses in aP versus wP vaccine recipients or unvaccinated, infected children. Recent data in experimental models, including primates, suggest that generation of vaccines capable of a potent, though regulated, stimulation of innate immunity driving effective, persistent adaptive immune responses againstBordetella pertussisinfection should be privileged. Adjuvants that skew Th1/Th17 responses or new wP (detoxified or attenuated) vaccines should be explored. Nonetheless, the high merits of the current aP vaccines in persuading people to resume vaccination against pertussis should not be forgotten.

scholarly journals Protective immune responses against West Nile virus are primed by distinct complement activation pathways

2006 ◽  
Vol 203 (5) ◽  
pp. 1371-1381 ◽  
Author(s):  
Erin Mehlhop ◽  
Michael S. Diamond
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
West Nile Virus ◽  
Immune Responses ◽  
Complement Activation ◽  
Adaptive Immune Responses ◽  
Cell Responses ◽  
Adaptive Immune ◽  
The Central Nervous System ◽  
Activation Pathways

West Nile virus (WNV) causes a severe infection of the central nervous system in several vertebrate animals including humans. Prior studies have shown that complement plays a critical role in controlling WNV infection in complement (C) 3−/− and complement receptor 1/2−/− mice. Here, we dissect the contributions of the individual complement activation pathways to the protection from WNV disease. Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread. In the absence of alternative pathway complement activation, WNV disseminated into the central nervous system at earlier times and was associated with reduced CD8+ T cell responses yet near normal anti-WNV antibody profiles. Animals lacking the classical and lectin pathways had deficits in both B and T cell responses to WNV. Finally, and somewhat surprisingly, C1q was required for productive infection in the spleen but not for development of adaptive immune responses after WNV infection. Our results suggest that individual pathways of complement activation control WNV infection by priming adaptive immune responses through distinct mechanisms.

VIP balances innate and adaptive immune responses induced by specific stimulation of TLR2 and TLR4

Peptides ◽  
2008 ◽  
Vol 29 (6) ◽  
pp. 948-956 ◽  
Author(s):  
Alicia Arranz ◽  
Yasmina Juarranz ◽  
Javier Leceta ◽  
Rosa P. Gomariz ◽  
Carmen Martínez
Keyword(s):  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Specific Stimulation ◽  
Stimulation Of

scholarly journals Local Cartilage Trauma as a Pathogenic Factor in Autoimmunity (One Hypothesis Based on Patients with Relapsing Polychondritis Triggered by Cartilage Trauma)

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Carlos A. Cañas ◽  
Fabio Bonilla Abadía
Keyword(s):  
Immune Responses ◽  
Inflammatory Process ◽  
Relapsing Polychondritis ◽  
Pathogenic Factor ◽  
Binding Mechanism ◽  
Adaptive Immune Responses ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Direct Association ◽  
Autoimmune Phenomena

In the recent years, it has been of great interest to study the binding mechanism between the innate and adaptive immune responses as interrelated processes for the development of multiple autoimmune diseases. Infection has been a well-known trigger of autoimmunity and trauma has been related as well too. Cryptogenic antigens release, recognition of pathogenic structure, and metabolic changes generated by both stimuli begin an inflammatory process which in turn activates the immune system amplifying T and B cell responses. The development of relapsing polychondritis after trauma may have a direct association with these events and in turn probably trigger autoimmune phenomena.

scholarly journals Quantal and graded stimulation of B lymphocytes as alternative strategies for regulating adaptive immune responses

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
E.D. Hawkins ◽  
M.L. Turner ◽  
C.J. Wellard ◽  
J.H.S. Zhou ◽  
M.R. Dowling ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Lymphocytes ◽  
Adaptive Immune Responses ◽  
Alternative Strategies ◽  
Adaptive Immune ◽  
Stimulation Of

scholarly journals Epithelial Phosphatidylinositol-3-Kinase Signaling Is Required for β-Catenin Activation and Host Defense against Citrobacter rodentium Infection

2011 ◽  
Vol 79 (5) ◽  
pp. 1863-1872 ◽  
Author(s):  
Jeffrey B. Brown ◽  
Paul Cheresh ◽  
Tatiana Goretsky ◽  
Elizabeth Managlia ◽  
Gery R. Grimm ◽  
...  
Keyword(s):  
Immune Responses ◽  
Host Defense ◽  
Bacterial Clearance ◽  
Phosphatidylinositol 3 Kinase ◽  
Adaptive Immune Responses ◽  
Content Type ◽  
Akt Activation ◽  
Adaptive Immune ◽  
Pi3k Inhibition ◽  
Pi3k Activation

ABSTRACTCitrobacter rodentiuminfection of mice induces cell-mediated immune responses associated with crypt hyperplasia and epithelial β-catenin signaling. Recent data suggest that phosphatidylinositol-3-kinase (PI3K)/Akt signaling cooperates with Wnt to activate β-catenin in intestinal stem and progenitor cells through phosphorylation at Ser552 (P-β-catenin552). Our aim was to determine whether epithelial PI3K/Akt activation is required for β-catenin signaling and host defense againstC. rodentium. C57BL/6 mice were infected withC. rodentiumand treated with dimethyl sulfoxide (DMSO) (vehicle control) or with the PI3K inhibitor LY294002 or wortmannin. The effects of infection on PI3K activation and β-catenin signaling were analyzed by immunohistochemistry. The effects of PI3K inhibition on host defense were analyzed by the quantification of splenic and colon bacterial clearance, and adaptive immune responses were measured by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Increased numbers of P-β-catenin552-stained epithelial cells were found throughout expanded crypts inC. rodentiumcolitis. We show that the inhibition of PI3K signaling attenuates epithelial Akt activation, the Ser552 phosphorylation and activation of β-catenin, and epithelial cell proliferative responses duringC. rodentiuminfection. PI3K inhibition impairs bacterial clearance despite having no impact on mucosal cytokine (gamma interferon [IFN-γ], tumor necrosis factor [TNF], interleukin-17 [IL-17], and IL-1β) or chemokine (CXCL1, CXCL5, CXCL9, and CXCL10) induction. The results suggest that the host defense againstC. rodentiumrequires epithelial PI3K activation to induce Akt-mediated β-catenin signaling and the clearance ofC. rodentiumindependent of adaptive immune responses.

scholarly journals Systems Immunology Analyses Following Porcine Respiratory and Reproductive Syndrome Virus Infection and Vaccination

2021 ◽  
Vol 12 ◽  
Author(s):  
Loïc Vivien Bocard ◽  
Andrew Robert Kick ◽  
Corinne Hug ◽  
Heidi Erika Lisa Lischer ◽  
Tobias Käser ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Innate Immune ◽  
Type I ◽  
Adaptive Immune Responses ◽  
Cell Responses ◽  
Adaptive Immune

This study was initiated to better understand the nature of innate immune responses and the relatively weak and delayed immune response against porcine reproductive and respiratory syndrome virus (PRRSV). Following modified live virus (MLV) vaccination or infection with two PRRSV-2 strains, we analyzed the transcriptome of peripheral blood mononuclear cells collected before and at three and seven days after vaccination or infection. We used blood transcriptional modules (BTMs)-based gene set enrichment analyses. BTMs related to innate immune processes were upregulated by PRRSV-2 strains but downregulated by MLV. In contrast, BTMs related to adaptive immune responses, in particular T cells and cell cycle, were downregulated by PRRSV-2 but upregulated by MLV. In addition, we found differences between the PRRSV strains. Only the more virulent strain induced a strong platelet activation, dendritic cell activation, interferon type I and plasma cell responses. We also calculated the correlations of BTM with the neutralizing antibody and the T-cell responses. Early downregulation (day 0–3) of dendritic cell and B-cell BTM correlated to both CD4 and CD8 T-cell responses. Furthermore, a late (day 3–7) upregulation of interferon type I modules strongly correlated to helper and regulatory T-cell responses, while inflammatory BTM upregulation correlated more to CD8 T-cell responses. BTM related to T cells had positive correlations at three days but negative associations at seven days post-infection. Taken together, this work contributes to resolve the complexity of the innate and adaptive immune responses against PRRSV and indicates a fundamentally different immune response to the less immunogenic MLV compared to field strains which induced robust adaptive immune responses. The identified correlates of T-cell responses will facilitate a rational approach to improve the immunogenicity of MLV.

scholarly journals Adaptive immunity and vaccination – Iron in the spotlight

2021 ◽  
Author(s):  
Alexandra E Preston ◽  
Hal Drakesmith ◽  
Joe N Frost
Keyword(s):  
Immune Responses ◽  
Therapeutic Interventions ◽  
Dietary Iron ◽  
Iron Availability ◽  
Adaptive Immune Responses ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Complex Processes ◽  
Key Factor ◽  
Potential Impact

Abstract Vaccination programmes are critically important to suppress the burden of infectious diseases, saving countless lives globally, as emphasized by the current COVID-19 pandemic. Effective adaptive immune responses are complex processes subject to multiple influences. Recent genetic, pre-clinical and clinical studies have converged to show that availability of iron is a key factor regulating the development of T and B cell responses to infection and immunization. Lymphocytes obtain iron from circulating transferrin. The amount of iron bound to transferrin is dependent on dietary iron availability and is decreased during inflammation via upregulation of the iron-regulatory hormone, hepcidin. As iron deficiency and chronic inflammatory states are both globally prevalent health problems, the potential impact of low iron availability on immune responses is significant. We describe the evidence supporting the importance of iron in immunity, highlight important unknowns, and discuss how therapeutic interventions to modulate iron availability might be implementable in the context of vaccination and infectious disease.

scholarly journals Induction of oligoclonal CD8 T cell responses against pulmonary metastatic cancer by a phospholipid-conjugated TLR7 agonist

2018 ◽  
Vol 115 (29) ◽  
pp. E6836-E6844 ◽  
Author(s):  
Tadashi Hosoya ◽  
Fumi Sato-Kaneko ◽  
Alast Ahmadi ◽  
Shiyin Yao ◽  
Fitzgerald Lao ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Lung Metastases ◽  
Adaptive Immune Responses ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Tlr7 Agonist ◽  
Cancer Models ◽  
Tcr Repertoire ◽  
4T1 Breast Cancer

Recent advances in cancer immunotherapy have improved patient survival. However, only a minority of patients with pulmonary metastatic disease respond to treatment with checkpoint inhibitors. As an alternate approach, we have tested the ability of systemically administered 1V270, a toll-like receptor 7 (TLR7) agonist conjugated to a phospholipid, to inhibit lung metastases in two variant murine 4T1 breast cancer models, as well as in B16 melanoma, and Lewis lung carcinoma models. In the 4T1 breast cancer models, 1V270 therapy inhibited lung metastases if given up to a week after primary tumor initiation. The treatment protocol was facilitated by the minimal toxic effects exerted by the phospholipid TLR7 agonist compared with the unconjugated agonist. 1V270 exhibited a wide therapeutic window and minimal off-target receptor binding. The 1V270 therapy inhibited colonization by tumor cells in the lungs in an NK cell dependent manner. Additional experiments revealed that single administration of 1V270 led to tumor-specific CD8+ cell-dependent adaptive immune responses that suppressed late-stage metastatic tumor growth in the lungs. T cell receptor (TCR) repertoire analyses showed that 1V270 therapy induced oligoclonal T cells in the lungs and mediastinal lymph nodes. Different animals displayed commonly shared TCR clones following 1V270 therapy. Intranasal administration of 1V270 also suppressed lung metastasis and induced tumor-specific adaptive immune responses. These results indicate that systemic 1V270 therapy can induce tumor-specific cytotoxic T cell responses to pulmonary metastatic cancers and that TCR repertoire analyses can be used to monitor, and to predict, the response to therapy.

scholarly journals High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharide-induced immune responses

2011 ◽  
Vol 209 (1) ◽  
pp. 157-171 ◽  
Author(s):  
De Yang ◽  
Yuri V. Postnikov ◽  
Yana Li ◽  
Poonam Tewary ◽  
Gonzalo de la Rosa ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Specific Antibody ◽  
High Mobility ◽  
T Cell Responses ◽  
High Mobility Group ◽  
Adaptive Immune Responses ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Nucleosome Binding

Alarmins are endogenous mediators capable of promoting the recruitment and activation of antigen-presenting cells (APCs), including dendritic cells (DCs), that can potentially alert host defense against danger signals. However, the relevance of alarmins to the induction of adaptive immune responses remains to be demonstrated. In this study, we report the identification of HMGN1 (high-mobility group nucleosome-binding protein 1) as a novel alarmin and demonstrate that it contributes to the induction of antigen-specific immune responses. HMGN1 induced DC maturation via TLR4 (Toll-like receptor 4), recruitment of APCs at sites of injection, and activation of NF-κB and multiple mitogen-activated protein kinases in DCs. HMGN1 promoted antigen-specific immune response upon co-administration with antigens, and Hmgn1−/− mice developed greatly reduced antigen-specific antibody and T cell responses when immunized with antigens in the presence of lipopolysaccharide (LPS). The impaired ability of Hmgn1−/− mice to mount antigen-specific immune responses was accompanied by both deficient DC recruitment at sites of immunization and reduced production of inflammatory cytokines. Bone marrow chimera experiments revealed that HMGN1 derived from nonleukocytes was critical for the induction of antigen-specific antibody and T cell responses. Thus, extracellular HMGN1 acts as a novel alarmin critical for LPS-induced development of innate and adaptive immune responses.

SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

2020 ◽  
Author(s):  
Stine SF Nielsen ◽  
Line K Vibholm ◽  
Ida Monrad ◽  
Rikke Olesen ◽  
Giacomo S Frattari ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Disease Severity ◽  
Adaptive Immune Response ◽  
T Cell Responses ◽  
Adaptive Immune Responses ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Robust Adaptive

AbstractThe SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search for treatments and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. We investigated the breadth and potency of antibody-, and T-cell immune responses, in 203 recovered SARS-CoV-2 infected patients who presented with asymptomatic to severe infections. We report very broad serological profiles with cross-reactivity to other human coronaviruses. Further, >99% had SARS-CoV-2 epitope specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 95% of individuals. A significant positive correlation between spike-ACE2 blocking antibody titers and neutralization potency was observed. SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 90% of HLA-A2+ individuals. The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+ T cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of disease severity.Author summarySARS-CoV-2 can cause severe and deadly infections. However, the immunological understanding of this viral infection is limited. Currently, several vaccines are being developed to help limit transmission and prevent the current pandemic. However, basic understanding of the adaptive immune response developed during SARS-CoV-2 infections is needed to inform further vaccine development and to understand the protective properties of the developed immune response. We investigated, the adaptive immune response developed during SARS-CoV-2 infections in recovered patients experiencing a full spectrum of disease severity, from asymptomatic infections to severe cases requiring hospitalization. We used a novel multiplex serological platform, cell-based neutralization assays and dextramer flow cytometry assays to characterize a broad and robust humoral and cellular immune response towards SARS-CoV-2. We found that the vast majority of recovered individuals have clear detectable and functional SARS-CoV-2 spike specific adaptive immune responses, despite diverse disease severities. The detection of both a humoral and cellular functional spike specific immune response in the vast majority of the individuals, irrespective of asymptomatic manifestations, supports vaccine designs currently underway, and encourages further exploration of whether primary infections provide protection to reinfection.

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