scholarly journals A Weakened Immune Response to Synthetic Exo-Peptides Predicts a Potential Biosecurity Risk in the Retrieval of Exo-Microorganisms

2020 ◽  
Vol 8 (7) ◽  
pp. 1066
Author(s):  
Katja Schaefer ◽  
Ivy M. Dambuza ◽  
Sergio Dall’Angelo ◽  
Raif Yuecel ◽  
Marcel Jaspars ◽  
...  
Keyword(s):  
Amino Acids ◽  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Cell Activation ◽  
Life Forms ◽  
Microbial Life ◽  
Aminoisobutyric Acid ◽  
Peptide Antigens ◽  
Mammalian Immune System

The discovery of liquid water at several locations in the solar system raises the possibility that microbial life may have evolved outside Earth and as such could be accidently introduced into the Earth’s ecosystem. Unusual sugars or amino acids, like non-proteinogenic isovaline and α-aminoisobutyric acid that are vanishingly rare or absent from life forms on Earth, have been found in high abundance on non-terrestrial carbonaceous meteorites. It is therefore conceivable that exo-microorganisms might contain proteins that include these rare amino acids. We therefore asked whether the mammalian immune system would be able to recognize and induce appropriate immune responses to putative proteinaceous antigens that include these rare amino acids. To address this, we synthesised peptide antigens based on a backbone of ovalbumin and introduced isovaline and α-aminoisobutyric acid residues and demonstrated that these peptides can promote naïve OT-I cell activation and proliferation, but did so less efficiently than the canonical peptides. This is relevant to the biosecurity of missions that may retrieve samples from exoplanets and moons that have conditions that may be permissive for life, suggesting that accidental contamination and exposure to exo-microorganisms with such distinct proteomes might pose an immunological challenge.

Next Generation of Immunotherapy for Melanoma

2008 ◽  
Vol 26 (20) ◽  
pp. 3445-3455 ◽  
Author(s):  
John M. Kirkwood ◽  
Ahmad A. Tarhini ◽  
Monica C. Panelli ◽  
Stergios J. Moschos ◽  
Hassane M. Zarour ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
The United States ◽  
Cytotoxic Agents ◽  
Antitumor Immune Response ◽  
Phase Iii

PurposeImmunotherapy has a long history with striking but limited success in patients with melanoma. To date, interleukin-2 and interferon-alfa2b are the only approved immunotherapeutic agents for melanoma in the United States.DesignTumor evasion of host immune responses, and strategies for overcoming tumor-induced immunosuppression are reviewed. Several novel immunotherapies currently in worldwide phase III clinical testing for melanoma are discussed.ResultsThe limitations of immunotherapy for melanoma stem from tumor-induced mechanisms of immune evasion that render the host tolerant of tumor antigens. For example, melanoma inhibits the maturation of antigen-presenting cells, preventing full T-cell activation and downregulating the effector antitumor immune response. New immunotherapies targeting critical regulatory elements of the immune system may overcome tolerance and promote a more effective antitumor immune response. These include monoclonal antibodies that block the cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and toll-like receptor 9 (TLR9) agonists. Blockade of CTLA4 prevents inhibitory signals that downregulate T-cell activation. TLR9 agonists stimulate dendritic cell maturation and ultimately induce a more effective immune response. These approaches have been shown to stimulate acute immune activation with concomitant appearance of transient adverse events mediated by the immune system. The pattern and duration of immune responses associated with these new modalities differ from those associated with cytokines and cytotoxic agents. In addition, vaccines are being developed that may ultimately target melanoma either alone or in combination with these immunomodulatory therapies.ConclusionThe successes of cytokine and interferon therapy of melanoma, coupled with an array of new approaches, are generating new enthusiasm for the immunotherapy of melanoma.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Unlocking the Potential of Vaccines Built on Messenger RNA

2021 ◽  
pp. 160-197
Author(s):  
Elena Locci ◽  
Silvia Raymond
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Side Effects ◽  
Immune Responses ◽  
Messenger Rna ◽  
Healthy Tissue ◽  
Therapeutic Approaches ◽  
Inflammatory Reactions ◽  
Discontinuation Of Treatment ◽  
Keywords Cancer

In recent years, immunotherapy has revolutionized the treatment of cancer; however, inflammatory reactions in healthy tissues often have side effects that can be serious and lead to permanent discontinuation of treatment. This toxicity is not yet well understood and is a major obstacle to the use of immunotherapy. When the immune system is so severely activated, the resulting inflammatory reaction can have detrimental effects and sometimes serious damage to healthy tissue. We wanted to know if there was a difference between an optimal immune response that aims to kill cancer and an unwanted response that could affect healthy tissue. Identifying the distinctive elements between these two immune responses allows the development of new, more effective and less toxic therapeutic approaches. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

Introduction to Clinical Immunology: Overview of the Immune Response, Autoimmune Conditions, and Immunosuppressive Therapeutics for Rheumatic Diseases

2016 ◽  
Author(s):  
Steven K. Lundy ◽  
Alison Gizinski ◽  
David A. Fox
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune

The immune system is a complex network of cells and mediators that must balance the task of protecting the host from invasive threats. From a clinical perspective, many diseases and conditions have an obvious link to improper functioning of the immune system, and insufficient immune responses can lead to uncontrolled acute and chronic infections. The immune system may also be important in tumor surveillance and control, cardiovascular disease, health complications related to obesity, neuromuscular diseases, depression, and dementia. Thus, a working knowledge of the role of immunity in disease processes is becoming increasingly important in almost all aspects of clinical practice. This review provides an overview of the immune response and discusses immune cell populations and major branches of immunity, compartmentalization and specialized immune niches, antigen recognition in innate and adaptive immunity, immune tolerance toward self antigens, inflammation and innate immune responses, adaptive immune responses and helper T (Th) cell subsets, components of the immune response that are important targets of treatment in autoimmune diseases, mechanisms of action of biologics used to treat autoimmune diseases and their approved uses, and mechanisms of other drugs commonly used in the treatment of autoimmune diseases. Figures show the development of erythrocytes, platelets, lymphocytes, and other immune system cells originating from hematopoietic stem cells that first reside in the fetal liver and later migrate to the bone marrow, antigen–major histocompatibility complex recognition by T cell receptor control of T cell survival and activation, and Th cells as central determinants of the adaptive immune response toward different stimuli. Tables list cell populations involved in innate and adaptive immunity, pattern recognition receptors with known ligands, autoantibody-mediated human diseases: examples of pathogenic mechanisms, selected Food and Drug Administration–approved autoimmune disease indications for biologics, and mechanism of action of biologics used to treat autoimmune diseases.   This review contains 3 highly rendered figures, 5 tables, and 64 references.

The Interaction of Antigens and Superantigens with the Human Class II Major Histocompatibility Complex Molecule HLA-DR1

1997 ◽  
Author(s):  
T. Jardetzky
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Immune System ◽  
Complex Molecule ◽  
Thymic Selection ◽  
Major Histocompatibility ◽  
Peptide Antigens ◽  
Histocompatibility Complex ◽  
Unique Specificity

The initiation and maintenance of an immune response to pathogens requires the interactions of cells and proteins that together are able to distinguish appropriate non-self targets from the myriadof self-proteins (Janeway and Bottomly, 1994). This discrimination between self and non-self is in part accomplished by three groups of proteins of the immune system that have direct and specific interactions with antigens: antibodies, T cell receptors (TcR) and major histocompatibility complex (MHC) proteins. Antibodies and TcR molecules are clonally expressed by the B and T cells of the immune system, respectively, defining each progenitor cell with a unique specificity for antigen. In these cell types both antibodies and TcR proteins undergo similar recombination events to generate a variable antigen combining site and thus produce a nearly unlimited number of proteins of different specificities. TcR molecules are further selected to recognize antigenic peptides bound to MHC proteins, during a process known as thymic selection, restricting the repertoire of T cells to the recognition of antigens presented by cells that express MHC proteins at their surface. Thymic selection of TcR and the subsequent restricted recognition of peptide-MHC complexes by peripheral T cells provides a fundamental molecular basis for the discrimination of self from non-sell and the regulation of the immune response (Allen, 1994; Nossal, 1994; von Boehmer, 1994). For example, different classes of T cells are used to recognize and kill infected cells (cytotoxic T cells) arid to provide lymphokiries that induce the niajority of soluble antibody responses of B cells (helper T cells). In contrast to the vast combinatorial and clonal diversity of antibodies and TcRs, a small set of MHC molecules is used to recognize a potentially unlimited universe of foreign peptide antigens for antigen presentation to T cells (Germain, 1994). This poses the problem of how each MHC molecule is capable of recognizing enough peptides to insure an immune response to pathogens. In addition, the specificity of the TcR interaction with MHC-peptide complexes is clearly crucial to the problem of self :non-self discrimination, with implications for both protective immunity and auto-immune disease.

scholarly journals Role of the microbiome in human development

Gut ◽  
2019 ◽  
Vol 68 (6) ◽  
pp. 1108-1114 ◽  
Author(s):  
Maria Gloria Dominguez-Bello ◽  
Filipa Godoy-Vitorino ◽  
Rob Knight ◽  
Martin J Blaser
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Human Development ◽  
Life Forms ◽  
Host Responses ◽  
Host Immune System ◽  
Next Generation ◽  
Host Health ◽  
Host Development

The host-microbiome supraorganism appears to have coevolved and the unperturbed microbial component of the dyad renders host health sustainable. This coevolution has likely shaped evolving phenotypes in all life forms on this predominantly microbial planet. The microbiota seems to exert effects on the next generation from gestation, via maternal microbiota and immune responses. The microbiota ecosystems develop, restricted to their epithelial niches by the host immune system, concomitantly with the host chronological development, providing early modulation of physiological host development and functions for nutrition, immunity and resistance to pathogens at all ages. Here, we review the role of the microbiome in human development, including evolutionary considerations, and the maternal/fetal relationships, contributions to nutrition and growth. We also discuss what constitutes a healthy microbiota, how antimicrobial modern practices are impacting the human microbiota, the associations between microbiota perturbations, host responses and diseases rocketing in urban societies and potential for future restoration.

scholarly journals Phenoloxidase activity and haemolymph cytology in honeybees challenged with a virus suspension (deformed wings virus DWV) or phosphate buffered suspension (PBS)

2019 ◽  
Vol 49 (2) ◽  
Author(s):  
Francesca Millanta ◽  
Simona Sagona ◽  
Maurizio Mazzei ◽  
Mario Forzan ◽  
Alessandro Poli ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Innate Immune System ◽  
Innate Immune ◽  
Additional Stress ◽  
Varroa Mite ◽  
Virus Suspension ◽  
Phenoloxidase Activity ◽  
Cell Immunity

ABSTRACT: The innate immune system of honeybees mainly consists in antimicrobial peptides, cellular immunity and melanisation. In order to investigate the immune response of honeybees to immune stressors, three stress degrees were tested. Newly emerged bees naturally DWV-infected were collected from a Varroa mite-free apiary and divided into three experimental groups: naturally DWV infected bees, PBS injected bees, and artificially DWV super infected bees. Phenoloxidase activity and haemolymph cellular subtype count were investigated. Phenoloxidase activity was highest (P<0.05) in DWV-superinfected bees, and the haemocyte population differed within the three observed groups. Although, immune responses following DWV infection have still not been completely clarified, this investigation sheds light on the relation between cell immunity and the phenoloxidase activity of DWV-naturally infected honeybees exposed to additional stress such as injury and viral superinfection.

scholarly journals Helminth Parasites Alter Protection againstPlasmodiumInfection

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Víctor H. Salazar-Castañon ◽  
Martha Legorreta-Herrera ◽  
Miriam Rodriguez-Sosa
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Parasite Density ◽  
Parasitic Disease ◽  
Helminth Parasites ◽  
Helminth Infections ◽  
Helminthic Infections ◽  
Severity Of The Disease ◽  
Type Response

More than one-third of the world’s population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host’s immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths andPlasmodiumaffects the host’s immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host’s susceptibility to subsequent infections byPlasmodium. There are a number of reports on the interactions between helminths andPlasmodium; in some, the burden ofPlasmodiumparasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodiumcoinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response.

scholarly journals Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance

2014 ◽  
Vol 112 (2) ◽  
pp. E156-E165 ◽  
Author(s):  
Roberto A. Maldonado ◽  
Robert A. LaMothe ◽  
Joseph D. Ferrari ◽  
Ai-Hong Zhang ◽  
Robert J. Rossi ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Coagulation Factor ◽  
Immunological Tolerance ◽  
Immunosuppressive Drugs ◽  
Free Form ◽  
Peptide Antigens ◽  
Humoral Immune ◽  
Novel Approach

Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists. Treatment with tolerogenic nanoparticles results in the inhibition of CD4+ and CD8+ T-cell activation, an increase in regulatory cells, durable B-cell tolerance resistant to multiple immunogenic challenges, and the inhibition of antigen-specific hypersensitivity reactions, relapsing experimental autoimmune encephalomyelitis, and antibody responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized to antigen. Only encapsulated rapamycin, not the free form, could induce immunological tolerance. Tolerogenic nanoparticle therapy represents a potential novel approach for the treatment of allergies, autoimmune diseases, and prevention of antidrug antibodies against biologic therapies.

The role of cytokines in immunological tolerance: potential for therapy

2000 ◽  
Vol 2 (9) ◽  
pp. 1-20 ◽  
Author(s):  
Mark Harber ◽  
Anette Sundstedt ◽  
David Wraith
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Animal Models ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immunological Tolerance ◽  
Immunomodulatory Effects ◽  
Clinical Potential

Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

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