The Innate Immune Response to Adjuvants Dictates the Adaptive Immune Response to Autoantigens

Bovine Viral Diarrhea Virus (BVDV) fetal infections occur in two forms; persistent infection (PI) or transient infection (TI), depending on what stage of gestation the fetus is infected. Examination of lymphoid organs from both PI and TI fetuses reveals drastically different fetal responses, dependent upon the developmental stage of the fetal immune system. Total RNA was extracted from the thymuses and spleens of uninfected control, PI, and TI fetuses collected on day 190 of gestation to test the hypothesis that BVDV infection impairs the innate and adaptive immune response in the fetal thymus and spleen of both infection types. Transcripts of genes representing the innate immune response and adaptive immune response genes were assayed by Reverse Transcription quatitative PCR (RT-qPCR) (2−ΔΔCq; fold change). Genes of the innate immune response, interferon (IFN) inducible genes, antigen presentation to lymphocytes, and activation of B cells were downregulated in day 190 fetal PI thymuses compared to controls. In contrast, innate immune response genes were upregulated in TI fetal thymuses compared to controls and tended to be upregulated in TI fetal spleens. Genes associated with the innate immune system were not different in PI fetal spleens; however, adaptive immune system genes were downregulated, indicating that PI fetal BVDV infection has profound inhibitory effects on the expression of genes involved in the innate and adaptive immune response. The downregulation of these genes in lymphocytes and antigen-presenting cells in the developing thymus and spleen may explain the incomplete clearance of BVDV and the persistence of the virus in PI animals while the upregulation of the TI innate immune response indicates a more mature immune system, able to clear the virus.

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Plant Phenolics and Lectins as Vaccine Adjuvants

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190716110705 ◽

2019 ◽

Vol 20 (15) ◽

pp. 1236-1243 ◽

Cited By ~ 2

Author(s):

Hernández-Ramos Reyna-Margarita ◽

Castillo-Maldonado Irais ◽

Rivera-Guillén Mario-Alberto ◽

Ramírez-Moreno Agustina ◽

Serrano-Gallardo Luis-Benjamín ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

The Body ◽

Innate Immune ◽

Vaccine Adjuvants ◽

Plant Phenolics ◽

Adaptive Immune ◽

Foreign Substance

Background: The immune system is responsible for providing protection to the body against foreign substances. The immune system divides into two types of immune responses to study its mechanisms of protection: 1) Innate and 2) Adaptive. The innate immune response represents the first protective barrier of the organism that also works as a regulator of the adaptive immune response, if evaded the mechanisms of the innate immune response by the foreign substance the adaptive immune response takes action with the consequent antigen neutralization or elimination. The adaptive immune response objective is developing a specific humoral response that consists in the production of soluble proteins known as antibodies capable of specifically recognizing the foreign agent; such protective mechanism is induced artificially through an immunization or vaccination. Unfortunately, the immunogenicity of the antigens is an intrinsic characteristic of the same antigen dependent on several factors. Conclusion: Vaccine adjuvants are chemical substances of very varied structure that seek to improve the immunogenicity of antigens. The main four types of adjuvants under investigation are the following: 1) Oil emulsions with an antigen in solution, 2) Pattern recognition receptors activating molecules, 3) Inflammatory stimulatory molecules or activators of the inflammasome complex, and 4) Cytokines. However, this paper addresses the biological plausibility of two phytochemical compounds as vaccine adjuvants: 5) Lectins, and 6) Plant phenolics whose characteristics, mechanisms of action and disadvantages are addressed. Finally, the immunological usefulness of these molecules is discussed through immunological data to estimate effects of plant phenolics and lectins as vaccine adjuvants, and current studies that have implanted these molecules as vaccine adjuvants, demonstrating the results of this immunization.

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The Metabolic Phenotype Associated with Mounting an Immune Response to a Systemic Infection of Listeria Monocytogenes (FS12-07-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz049.fs12-07-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Robert Johnson ◽

Adesola Olatunde ◽

Lauren Woodie ◽

Michael Greene ◽

Elizabeth Schwartz

Keyword(s):

Immune Response ◽

Bacterial Infection ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

Innate Immune ◽

Metabolic Phenotype ◽

Metabolic Demand ◽

Pathogen Infection ◽

Full Spectrum ◽

Adaptive Immune

Abstract Objectives Our goal in these studies was to quantitatively determine the metabolic phenotype of intracellular bacterial infection, immune response, and clearance. Mounting an immune response to a bacterial infection is metabolically taxing to the host. During infection, the host exhibits sickness syndrome characterized by fever, lethargy and anorexia. Cells of the immune system also shift cellular metabolic pathways, which alters the metabolic and nutritional needs of the host. Previous studies of the metabolic demands of sickness have used model antigens, mitogens or pattern associated molecular patterns, which do not represent the full spectrum of response to a live pathogen infection. Thus, our study is the first of its kind to assess the full spectrum of metabolic, nutritional, immunological, and behavioral demands of live pathogen infection. Methods Mice were administered either a mock intraperitoneal (ip) injection of PBS (Control) or ip dose of Listeria and individually housed over the course of 12 days in Promethion metabolic cages to monitor their metabolic phenotype. In a parallel study, groups of mice were equivalently treated, yet conventionally housed and sacrificed at 3, 5, 7 and 10 days over the course of infection to determine splenic bacterial burden, Listeria-specific T cell response, and cellular metabolic status. Results We observed that the period of the innate immune response (days 1–4) had the most metabolic demand, indicated by weight loss (P < 0.05), reduced activity (P < 0.05), increased sleep (P < 0.05), and decreased energy expenditure (P < 0.05). During the period of the adaptive immune response (days 5–10), there was little to no metabolic impact in the infected animals when compared to the uninfected control animals. We also observed increased GLUT1 expression (P < 0.05) on the membranes of myeloid cells during the period of highest metabolic demand, indicating shifts in cellular metabolism of innate immune cells during the early stages of infection. Conclusions The innate immune response is more metabolically taxing on the host compared to the adaptive immune response and places an increased metabolic demand on infected animals. Funding Sources Departmental startup funds to Elizabeth Hiltbold Schwartz.

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Replicon Particles of Venezuelan Equine Encephalitis Virus as a Reductionist Murine Model for Encephalitis

Journal of Virology ◽

10.1128/jvi.02383-08 ◽

2009 ◽

Vol 83 (9) ◽

pp. 4275-4286 ◽

Cited By ~ 20

Author(s):

Alexandra Schäfer ◽

Alan C. Whitmore ◽

Jennifer L. Konopka ◽

Robert E. Johnston

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

Venezuelan Equine Encephalitis Virus ◽

Encephalitis Virus ◽

Innate Immune ◽

Venezuelan Equine Encephalitis ◽

Equine Encephalitis Virus ◽

Adaptive Immune ◽

Inflammatory Monocytes

ABSTRACT Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) were used to model the initial phase of VEE-induced encephalitis in the mouse brain. VRP can target and infect cells as VEE, but VRP do not propagate beyond the first infected cell due to the absence of the structural genes. Direct intracranial inoculation of VRP into mice induced acute encephalitis with signs similar to the neuronal phase of wild-type VEE infection and other models of virus-induced encephalitis. Using the previously established VRP-mRNP tagging system, a new method to distinguish the host responses in infected cells from those in uninfected bystander cell populations, we detected a robust and rapid innate immune response in the central nervous system (CNS) by infected neurons and uninfected bystander cells. Moreover, this innate immune response in the CNS compromised blood-brain barrier integrity, created an inflammatory response, and directed an adaptive immune response characterized by proliferation and activation of microglia cells and infiltration of inflammatory monocytes, in addition to CD4+ and CD8+ T lymphocytes. Taken together, these data suggest that a naïve CNS has an intrinsic potential to induce an innate immune response that could be crucial to the outcome of the infection by determining the composition and dynamics of the adaptive immune response. Furthermore, these results establish a model for neurotropic virus infection to identify host and viral factors that contribute to invasion of the brain, the mechanism(s) whereby the adaptive immune response can clear the infection, and the role of the host innate response in these processes.

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Mecanismos de la respuesta inmune innata... la primera línea de defensa

RA RIÓ GUENDARUYUBI ◽

10.53331/rar.v3i8.2583 ◽

2020 ◽

Vol 3 (8) ◽

pp. 6-24

Author(s):

Ángeles Esmeralda Gómez-Bustamante ◽

Hermes Jared Morales-López ◽

Honorio Torres-Aguilar

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

Innate Immune ◽

Twentieth Century Literature ◽

Prevention Strategies ◽

First Line ◽

Adaptive Immune ◽

Precision Level ◽

Century Literature

The twentieth century literature referred to the innate immune response as “unspecific”. Nevertheless, since the 1980s, the set of receptors that this kind of immune response cells –considered as the first line of defense– employ to directly recognize conserved molecules within a class of microbes, has been gradually described. This trait has turned the innate immune response highly specific when it comes to the recognition of microorganisms, but without reaching the high precision level of the adaptive immune response. This chapter describes the surveillance and prevention strategies, as well as the cellular and humoral mechanisms that the immune system immediately triggers against the first attempted aggression of an invading agent.

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A spontaneous multifunctional hydrogel vaccine amplifies the innate immune response to launch a powerful antitumor adaptive immune response

Theranostics ◽

10.7150/thno.58173 ◽

2021 ◽

Vol 11 (14) ◽

pp. 6936-6949

Author(s):

Xiuqi Liang ◽

Lu Li ◽

Xinchao Li ◽

Tao He ◽

Songlin Gong ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

Innate Immune ◽

Adaptive Immune

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The Innate Immune Response Characterizes Posterior Reversible Encephalopathy Syndrome

Journal of Clinical Immunology ◽

10.1007/s10875-021-01033-3 ◽

2021 ◽

Author(s):

Christopher Nelke ◽

Andreas Schulte-Mecklenbeck ◽

Marc Pawlitzki ◽

Leoni Rolfes ◽

Saskia Räuber ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Posterior Reversible Encephalopathy Syndrome ◽

Adaptive Immune Response ◽

Surrogate Marker ◽

Innate Immune ◽

Posterior Reversible Encephalopathy ◽

Adaptive Immune ◽

Multiple Sclerosis Patients ◽

Reversible Encephalopathy

AbstractWhile posterior reversible encephalopathy syndrome (PRES) is often characterized by an inflammatory cerebrospinal-fluid (CSF) profile, knowledge of immune cell patterns in PRES is lacking. Thus, we retrospectively characterized CSF and peripheral blood (PB) from 15 PRES patients, which we analyzed by multidimensional flow cytometry (FC). Results were compared to 72 controls, as well as to 9 patients with progressive multifocal leukoencephalopathy (PML, as a relevant differential diagnosis) and 15 multiple sclerosis patients (MS, as a classical neuroinflammatory disorder), respectively. Total protein level in CSF from PRES patients was elevated compared to that in controls, but not to MS and PML. In-depth FC analysis revealed no differences for adaptive immune cells (B cells, plasma cells, CD4+, and CD8+ T cells) in PB or CSF of PRES compared to controls. In contrast, we observed alterations of the adaptive immune response in CSF of PML and MS compared to PRES, indicating that the adaptive immune response is not a driver of disease in PRES. Indeed, PRES was characterized by an innate immune response with CD14++/CD16+ (intermediate) monocytes elevated in PB and CSF, while CD14++/CD16− (classical) monocytes were decreased in PB from PRES patients as compared to controls. Levels of CD14++/CD16+ monocytes correlated with the duration of hospital stay as a surrogate marker for disease severity in PRES patients. Our findings argue for a role of innate rather than adaptive immunity in the pathophysiology of PRES. The observed shift in monocyte subsets might provide valuable diagnostic clues for the clinical management of these patients.

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Adaptive immunity

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0040 ◽

2020 ◽

pp. 325-336

Author(s):

Paul Klenerman

Keyword(s):

Immune Response ◽

Immune Responses ◽

Adaptive Immunity ◽

Innate Immune Response ◽

Molecular Basis ◽

Adaptive Immune Response ◽

Antigenic Specificity ◽

Adaptive Immune Responses ◽

Research Attention ◽

Adaptive Immune

The adaptive immune response is distinguished from the innate immune response by two main features: its capacity to respond flexibly to new, previously unencountered antigens (antigenic specificity), and its enhanced capacity to respond to previously encountered antigens (immunological memory). These two features have provided the focus for much research attention, from the time of Jenner, through Pasteur onwards. Historically, innate and adaptive immune responses have often been treated as separate, with the latter being considered more ‘advanced’ because of its flexibility. It is now clear this not the case, and in recent years the molecular basis for these phenomena has become much better understood.

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