scholarly journals Characteristics of immune response to protozoan infections

2003 ◽  
Vol 56 (11-12) ◽  
pp. 557-563 ◽  
Author(s):  
Valentina Arsic-Arsenijevic ◽  
Aleksandar Dzamic ◽  
Sanja Mitrovic ◽  
Ivana Radonjic ◽  
Ivana Kranjcic-Zec
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
T Cell Activation ◽  
Defense Mechanisms ◽  
Cell Activation ◽  
Blood Stream ◽  
Biochemical Properties ◽  
Natural Immunity ◽  
Humoral Immune ◽  
Specific Immunity

Introduction When protozoa enter the blood stream or tissues they can often survive and replicate because they adapt to the resisting natural host defenses. The interaction of immune system with infectious organisms is a dynamic interplay of host mechanisms aimed at eliminating infections and microbial strategies designed to permit survival in the face of powerful effectors mechanisms. Protozoa cause chronic and persistent infections, because natural immunity against them is weak and because protozoa have evolved multiple mechanisms for evading and resisting specific immunity. Natural and specific immune response to protozoa Different protozoa vary greatly in their structural and biochemical properties and stimulate distinct patterns of immune responses and have evolved unique mechanisms for evading specific immunity. Protozoa activate quite distinct specific immune responses, which are different from the responses to fungi, bacteria and viruses. Protozoa may be phagocytozed by macrophages, but many are resistant to phagocytic killing and may even replicate within macrophages. T. brucei gambiense is the best example of protozoa which can induce humoral immune response because of its extra-cellular location. In Leishmania sp. infections, cellular defense mechanisms depend upon CD4+ T-lymphocytes and activate macrophages as effectors cells that are regulated by cytokines of Th1 subset. Plasmodium sp. is a protozoa which show the diversity of defence mechanisms which can be cellular or humoral, depending on Ag and protozoa's location. Immune evasion mechanisms of protozoa Different protozoa have developed remarkably effective ways of resisting specific immunity: a) anatomic sequestration is commonly observed with protozoa Plasmodium and T. gondii; b) some protozoa can become resistant to immune effectors mechanisms: Trypanosoma, Leishmania and T. gondii; c) some protozoa have developed effective mechanisms for varying their surface antigens: Plasmodium and Trypanosoma; d) some protozoa shed their antigen coats, either spontaneously or after binding with specific antibodies: E. histolytica; e) some protozoa alter host immune response by nonspecific and generalized immunosuppression (abnormalities in cytokine production, deficient T cell activation): Trypanosoma, Leishmania, Toxoplasma, Entamoeba. Conclusion Protozoa activate numerous, different immune mechanisms in human body. Evolution, progression and outcome of diseases depend upon these mechanisms. Resent progresses in research have defined and selected Ag as candidates for new vaccines. Better definitions regarding the role of cytokines in protozoaninfections will facilitate rational development of cytokines and cytokine antagonists and their use as immunotherapeutic agents.

scholarly journals Cellular and humoral immune responses associated with protection in sheep vaccinated against Teladorsagia circumcincta

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Cynthia Machín ◽  
Yolanda Corripio-Miyar ◽  
Julia N. Hernández ◽  
Tara Pérez-Hernández ◽  
Adam D. Hayward ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Anthelmintic Resistance ◽  
Gastrointestinal Nematodes ◽  
Control Group ◽  
Sheep Breeds ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Teladorsagia Circumcincta

AbstractDue to increased anthelmintic resistance, complementary methods to drugs are necessary to control gastrointestinal nematodes (GIN). Vaccines are an environmentally-friendly and promising option. In a previous study, a Teladorsagia circumcincta recombinant sub-unit vaccine was administered to two sheep breeds with different levels of resistance against GIN. In the susceptible Canaria Sheep (CS) breed, vaccinates harboured smaller worms with fewer eggs in utero than the control group. Here, we extend this work, by investigating the cellular and humoral immune responses of these two sheep breeds following vaccination and experimental infection with T. circumcincta. In the vaccinated CS group, negative associations between antigen-specific IgA, IgG2 and Globule Leukocytes (GLs) with several parasitological parameters were established as well as a higher CD4+/CD8+ ratio than in control CS animals, suggesting a key role in the protection induced by the vaccine. In the more resistant Canaria Hair Breed (CHB) sheep the vaccine did not significantly impact on the parasitological parameters studied and none of these humoral associations were observed in vaccinated CHB lambs, although CHB had higher proportions of CD4+ and CD8+ T cells within the abomasal lymph nodes, suggesting higher mucosal T cell activation. Each of the component proteins in the vaccine induced an increase in immunoglobulin levels in vaccinated groups of each breed. However, levels of immunoglobulins to only three of the antigens (Tci-MEP-1, Tci-SAA-1, Tci-ASP-1) were negatively correlated with parasitological parameters in the CS breed and they may be, at least partially, responsible for the protective effect of the vaccine in this breed. These data could be useful for improving the current vaccine prototype.

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.

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 New Insights into the Role of PD-1 and Its Ligands in Allergic Disease

2021 ◽  
Vol 22 (21) ◽  
pp. 11898
Author(s):  
Miguel Angel Galván Morales ◽  
Josaphat Miguel Montero-Vargas ◽  
Juan Carlos Vizuet-de-Rueda ◽  
Luis M. Teran
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Adaptive Immune Response ◽  
Allergic Diseases ◽  
Main Role ◽  
Pathway Regulation

Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2 are receptors that act in co-stimulatory and coinhibitory immune responses. Signaling the PD-1/PD-L1 or PD-L2 pathway is essential to regulate the inflammatory responses to infections, autoimmunity, and allergies, and it has been extensively studied in cancer. Allergic diseases include asthma, rhinoconjunctivitis, atopic dermatitis, drug allergy, and anaphylaxis. These overactive immune responses involve IgE-dependent activation and increased CD4+ T helper type 2 (Th2) lymphocytes. Recent studies have shown that PD-L1 and PD-L2 act to regulate T-cell activation and function. However, the main role of PD-1 and its ligands is to balance the immune response; however, the inflammatory process of allergic diseases is poorly understood. These immune checkpoint molecules can function as a brake or a kick-start to regulate the adaptive immune response. These findings suggest that PD-1 and its ligands may be a key factor in studying the exaggerated response in hypersensitivity reactions in allergies. This review summarizes the current understanding of the role of PD-1 and PD-L1 and PD-L2 pathway regulation in allergic diseases and how this immunomodulatory pathway is currently being targeted to develop novel therapeutic immunotherapy.

scholarly journals Interdependencies between cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination

2021 ◽  
Author(s):  
Moritz M Hollstein ◽  
Lennart Muensterkoetter ◽  
Michael P Schoen ◽  
Armin Bergmann ◽  
Thea M Husar ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
Booster Vaccination ◽  
Antibody Avidity ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Cellular Immune

Background: Homologous and heterologous SARS-CoV-2-vaccinations yield different spike protein-directed humoral and cellular immune responses. However, their interdependencies remain elusive. Methods: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received homologous vaccination with Astra (ChAdOx1-S; AstraZeneca) or BNT (BNT162b2; Biontech/Pfizer) or heterologous vaccination with Astra/BNT. We assessed the humoral (anti-spike-RBD-IgG, neutralizing antibodies, antibody avidity) and cellular (spike-induced T cell interferon-y release) immune response in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2). Findings: Initial vaccination with Astra resulted in lower anti-spike-RBD-IgG responses compared to BNT (70+/-114 vs. 226+/-279 BAU/ml, p<0.01) at T1, whereas T cell activation did not differ significantly. Booster vaccination with BNT proved superior to Astra at T2 (anti-spike-RBD-IgG: Astra/BNT 2387+/-1627 and BNT/BNT 3202+/-2184 vs. Astra/Astra 413+/-461 BAU/ml, both p<0.001; spike-induced T cell interferon-y; release: Astra/BNT 5069+/-6733 and BNT/BNT 4880+/-7570 vs. Astra/Astra 1152+/-2243 mIU/ml, both p<0.001). No significant differences were detected between BNT-boostered groups at T2. For Astra, we observed no booster effect on T cell activation. We found associations between anti-spike-RBD-IgG levels (Astra/BNT and BNT/BNT) and T cell responses (Astra/Astra and Astra/BNT) from T1 to T2. There were also links between levels of anti-spike-RBD-IgG and T cell at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Interpretation: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses. Funding: Deutsche Forschungsgemeinschaft (DFG), ER723/3-1

scholarly journals Functionalisation of Virus-Like Particles Enhances Antitumour Immune Responses

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Katrin Kramer ◽  
Farah Al-Barwani ◽  
Margaret A. Baird ◽  
Vivienne L. Young ◽  
David S. Larsen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mannose Receptor ◽  
Virus Like Particles ◽  
Rabbit Haemorrhagic Disease

Virus-like particles (VLP) from the rabbit haemorrhagic disease virus (RHDV) can deliver tumour antigens to induce anticancer immune responses. In this study, we explored how RHDV VLP can be functionalised to enhance the immune response by increasing antigen loading, incorporating linkers to enhance epitope processing, and targeting receptor-mediated internalisation of VLP. RHDV VLP were developed to deliver up to three copies of gp10025–33 which contained proteasome cleavable linkers to target the correct processing of the epitope. Addition of mono- and dimannosides, conjugated to the surface of the gp100 VLP, would utilise a second pathway of internalisation, mannose receptor mediated, to further augment antigen internalised by phagocytosis/macropinocytosis. In vitro cell culture studies showed that a processing linker at the C-terminus of the epitope (gp100.1LC) induced enhanced T-cell activation (7.3 ng/ml interferon- (IFN-) γ release) compared to no linker (3.0 ng/ml IFN-γ) or the linker at the N-terminus (0.8 ng/ml IFN-γ). VLP delivering two (gp100.2L) or three (gp100.3L) gp100 epitopes induced similar high T-cell activation (7.6 ng/ml IFN-γ) compared to gp100.1LC. An in vivo cytotoxicity assay and a therapeutic tumour trial confirmed that mice vaccinated with either gp100.2L or gp100.3L induced a specific antitumour immune response. Mannosylation of the gp100.2L VLP further enhanced the generated immune response, demonstrated by prolonged survival of mice vaccinated with dimannosylated gp100.2L VLP (D-gp100.2L) by 22 days compared to gp100.2L-vaccinated mice. This study showed that functionalisation of RHDV VLP by addition of an epitope-processing linker and mannosylation of the surface facilitates the efficacy of VLP as vaccination vectors for tumour immunotherapy.

scholarly journals MERS-CoV Spike Protein Vaccine and Inactivated Influenza Vaccine Formulated with Single Strand RNA Adjuvant Induce T-Cell Activation through Intranasal Immunization in Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 441
Author(s):  
Hye-Jung Kim ◽  
Hye Won Kwak ◽  
Kyung Won Kang ◽  
Yoo-Jin Bang ◽  
Yu-Sun Lee ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Influenza Vaccine ◽  
T Cell Activation ◽  
Humoral Immune Response ◽  
Cell Activation ◽  
Spike Protein ◽  
Intranasal Immunization ◽  
Humoral Immune ◽  
Inoculation Route

The effectiveness of vaccines is enhanced by adding adjuvants. Furthermore, the selection of an inoculation route depends on the type of adjuvant used and is important for achieving optimum vaccine efficacy. We investigated the immunological differences between two types of vaccines—spike protein from the Middle East respiratory syndrome virus and inactivated influenza virus vaccine, in combination with a single-stranded RNA adjuvant—administered through various routes (intramuscular, intradermal, and intranasal) to BALB/c mice. Intramuscular immunization with the RNA adjuvant-formulated spike protein elicited the highest humoral immune response, characterized by IgG1 and neutralizing antibody production. Although intranasal immunization did not elicit a humoral response, it showed extensive T-cell activation through large-scale induction of interferon-γ- and interleukin-2-secreting cells, as well as CD4+ T-cell activation in mouse splenocytes. Moreover, only intranasal immunization induced IgA production. When immunized with the inactivated influenza vaccine, administration of the RNA adjuvant via all routes led to protection after viral challenge, regardless of the presence of a vaccine-specific antibody. Therefore, the inoculation route should depend on the type of immune response needed; i.e., the intramuscular route is suitable for eliciting a humoral immune response, whereas the intranasal route is useful for T-cell activation and IgA induction.

scholarly journals Signaling through polymerization and degradation: Analysis and simulations of T cell activation mediated by Bcl10

2020 ◽  
Author(s):  
Leonard Campanello ◽  
Maria K. Traver ◽  
Hari Shroff ◽  
Brian C. Schaefer ◽  
Wolfgang Losert
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Super Resolution ◽  
Effector T Cells ◽  
Effector T Cell ◽  
Filament Assembly

AbstractThe adaptive immune system serves as a potent and highly specific defense mechanism against pathogen infection. One component of this system, the effector T cell, facilitates pathogen clearance upon detection of specific antigens by the T cell receptor (TCR). A critical process in effector T cell activation is transmission of signals from the TCR to a key transcriptional regulator, NF-κB. The transmission of this signal involves a highly dynamic process in which helical filaments of Bcl10, a key protein constituent of the TCR signaling cascade, undergo competing processes of polymeric assembly and macroautophagy-dependent degradation. Through computational analysis of three-dimensional super-resolution microscopy data, we quantitatively characterized TCR-stimulated Bcl10 filament assembly and length dynamics, demonstrating that filaments become shorter over time. Additionally, we developed an image-based bootstrap-like resampling method to quantitatively demonstrate preferred association between autophagosomes and Bcl10-filament ends and punctate-Bcl10 structures, implying that autophagosome-driven macroautophagy is directly responsible for Bcl10 filament shortening. We probe Bcl10 polymerization-depolymerization dynamics with a stochastic Monte-Carlo simulation of nucleation-limited filament assembly and degradation, and we show that high probabilities of filament nucleation in response to TCR engagement could provide the observed robust, homogeneous, and tunable response dynamic. Furthermore, the speed of autophagic degradation of filaments preferentially at filament ends provides effective regulatory control. Taken together, these data suggest that Bcl10 filament growth and degradation act as an excitable system that provides a digital response mechanism and the reliable timing critical for T cell activation and regulatory processes.Author SummaryThe immune system serves to protect organisms against pathogen-mediated disease. While a strong immune response is needed to eliminate pathogens in host organisms, immune responses that are too robust or too persistent can trigger autoimmune disorders, cancer, and a variety of additional serious human pathologies. Thus, a careful balance of activating and inhibitory mechanisms are necessary to prevent detrimental health outcomes of immune responses. For example, activated effector T cells marshal the immune response and direct killing of pathogen-infected cells; however, effector T cells that are chronically activated can damage and destroy healthy tissue. Here, we study an important internal activation pathway in effector T cells that involves the growth and counterbalancing degradation (via a process called macroautophagy) of filamentous cytoplasmic signaling structures. We utilize image analysis of 3-D super-resolution images and Monte Carlo simulations to study a key signal-transduction protein, Bcl10. We found that the speed of filament degradation has the greatest effect on the magnitude and duration of the response, implying that pharmaceutical interventions aimed at macroautophagy may have substantial impact on effector T cell function. Given that filamentous structures are utilized in numerous immune signaling pathways, our analysis methods could have broad applicability in the signal transduction field.

Antigen targeting to splenic CD169+ macrophages induces strong humoral immune responses and CD4+ T cell activation

2012 ◽  
Vol 51 (1) ◽  
pp. 12-13
Author(s):  
Henrike Veninga ◽  
Ellen Borg ◽  
Hakan Kalay ◽  
Yvette van Kooyk ◽  
Georg Kraal ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Notch2-dependent DC2s mediate splenic germinal center responses

2018 ◽  
Vol 115 (42) ◽  
pp. 10726-10731 ◽  
Author(s):  
Carlos G. Briseño ◽  
Ansuman T. Satpathy ◽  
Jesse T. Davidson ◽  
Stephen T. Ferris ◽  
Vivek Durai ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Humoral Immunity ◽  
Germinal Center ◽  
Cell Activation ◽  
Cell Formation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Follicular Helper

CD4+ T follicular helper (TFH) cells support germinal center (GC) reactions promoting humoral immunity. Dendritic cell (DC) diversification into genetically distinct subsets allows for specialization in promoting responses against several types of pathogens. Whether any classical DC (cDC) subset is required for humoral immunity is unknown, however. We tested several genetic models that selectively ablate distinct DC subsets in mice for their impact on splenic GC reactions. We identified a requirement for Notch2-dependent cDC2s, but not Batf3-dependent cDC1s or Klf4-dependent cDC2s, in promoting TFH and GC B cell formation in response to sheep red blood cells and inactivated Listeria monocytogenes. This effect was mediated independent of Il2ra and several Notch2-dependent genes expressed in cDC2s, including Stat4 and Havcr2. Notch2 signaling during cDC2 development also substantially reduced the efficiency of cDC2s for presentation of MHC class II-restricted antigens, limiting the strength of CD4 T cell activation. Together, these results demonstrate a nonredundant role for the Notch2-dependent cDC2 subset in supporting humoral immune responses.

Sign in / Sign up

Export Citation Format

Share Document