Highly glycosylated tumour antigens: interactions with the immune system

2011 ◽  
Vol 39 (1) ◽  
pp. 388-392 ◽  
Author(s):  
Eirikur Saeland ◽  
Yvette van Kooyk
Keyword(s):  
Immune System ◽  
Immune Modulation ◽  
Diagnostic Tools ◽  
Phenotypic Change ◽  
Carbohydrate Binding ◽  
Lectin Receptors ◽  
Functional Studies ◽  
Tumour Antigens ◽  
Antigen Presenting

A common phenotypic change in cancer is a dramatic transformation of cellular glycosylation. Functional studies of particular tumour-associated oligosaccharides are difficult to interpret conclusively, but carbohydrate-binding proteins are likely to contribute to progression of the tumour. This review discusses the potential role of CLRs (C-type lectin receptors), expressed by antigen-presenting cells of the immune system, in tumour recognition and immune modulation. Studies in recent years have provided significant insight into the immunomodulatory function of CLR during infections, but their role in cancer remains elusive; some strongly bind tumour cells and antigens, indicating participation in malignancy. The potential to use recombinant CLR as diagnostic tools will also be discussed.

scholarly journals The Role of Lectin Receptors and Their Ligands in Controlling Allergic Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Karin Peters ◽  
Marcus Peters
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Allergic Inflammation ◽  
Special Focus ◽  
Carbohydrate Binding ◽  
Lectin Receptors ◽  
Innate And Adaptive Immunity ◽  
Pathogen Recognition Receptors ◽  
Receptor Family

More than fifty c-type lectin receptors (CLR) are known and have been identified so far. Moreover, we know the group of galectins and sialic acid-binding immunoglobulin-type lectins that also belong to the carbohydrate-binding receptors of the immune system. Thus, the lectin receptors form the largest receptor family among the pathogen recognition receptors. Similar to the toll-like receptors (TLRs), the CLR do not only recognize foreign but also endogenous molecules. In contrast to TLRs, which have a predominantly activating effect on the immune system, lectin receptors also mediate inhibitory signals. They play an important role in innate and adaptive immunity for the induction, regulation and shaping of the immune response. The hygiene hypothesis links enhanced infection to protection from allergic disease. Yet, the microbial substances that are responsible for mediating this allergy-protective activity still have to be identified. Microbes contain both ligands binding to TLRs and carbohydrates that are recognized by CLR and other lectin receptors. In the current literature, the CLR are often recognized as the ‘bad guys’ in allergic inflammation, because some glycoepitopes of allergens have been shown to bind to CLR, facilitating their uptake and presentation. On the other hand, there are many reports revealing that sugar moieties are involved in immune regulation. In this review, we will summarize what is known about the role of carbohydrate interaction with c-type lectins and other sugar-recognizing receptors in anti-inflammation, with a special focus on the regulation of the allergic immune response.

Infection and immunity

2021 ◽  
pp. 853-920
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune System ◽  
Cell Types ◽  
The Body ◽  
Acquired Immunity ◽  
Histocompatibility Complex ◽  
Repair Mechanisms ◽  
Antigen Presenting ◽  
Different Cell Types

‘Infection and immunity’ considers the response of the body to pathogens, such as bacteria, viruses, prions, fungi, and parasites, which are discussed in terms of their nature, life cycle, and modes of infection. The role of the immune system in defence against infection is discussed, including innate and adaptive (acquired) immunity, antigens, the major histocompatibility complex, and the different cell types involved (antigen-presenting cells, T-cells, and B-cells). The mechanisms and cellular basis of inflammation are considered, as are post-infection repair mechanisms, and pathologies of the immune system such as hypersensitivity, autoimmunity and transplantations, and immunodeficiency (both primary and secondary to other diseases).

scholarly journals MGL Receptor and Immunity: When the Ligand Can Make the Difference

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ilaria Grazia Zizzari ◽  
Chiara Napoletano ◽  
Federico Battisti ◽  
Hassan Rahimi ◽  
Salvatore Caponnetto ◽  
...  
Keyword(s):  
Immune Response ◽  
Steric Structure ◽  
Activated Macrophages ◽  
Danger Signal ◽  
Lectin Receptors ◽  
Type C ◽  
The Difference ◽  
Antigen Presenting ◽  
Antigen Structure

C-type lectin receptors (CLRs) on antigen-presenting cells (APCs) facilitate uptake of carbohydrate antigens for antigen presentation, modulating the immune response in infection, homeostasis, autoimmunity, allergy, and cancer. In this review, we focus on the role of the macrophage galactose type C-type lectin (MGL) in the immune response against self-antigens, pathogens, and tumor associated antigens (TAA). MGL is a CLR exclusively expressed by dendritic cells (DCs) and activated macrophages (MØs), able to recognize terminal GalNAc residues, including the sialylated and nonsialylated Tn antigens. We discuss the effects on DC function induced throughout the engagement of MGL, highlighting the importance of the antigen structure in the modulation of immune response. Indeed modifying Tn-density, the length, and steric structure of the Tn-antigens can result in generating immunogens that can efficiently bind to MGL, strongly activate DCs, mimic the effects of a danger signal, and achieve an efficient presentation in HLA classes I and II compartments.

From mammals to viruses: the Schlafen genes in developmental, proliferative and immune processes

2011 ◽  
Vol 2 (3) ◽  
pp. 159-169 ◽  
Author(s):  
Elena de la Casa-Esperón
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Gene Family ◽  
Horizontal Transfer ◽  
Meiotic Drive ◽  
Embryonic Lethality ◽  
Widespread Distribution ◽  
Proliferation Control ◽  
Functional Studies

AbstractThe Schlafen genes have been associated with proliferation control and with several differentiation processes, as well as with disparate phenotypes such as immune response, embryonic lethality and meiotic drive. They constitute a gene family with widespread distribution in mammals, where they are expressed in several tissues, predominantly those of the immune system. Moreover, horizontal transfer of these genes to orthopoxviruses suggests a role of the viral Schlafens in evasion to the host immune response. The expression and functional studies of this gene family will be reviewed under the prism of their evolution and diversification, the challenges they pose and the future avenues of research.

Endocytic receptor for pro-coagulant factor VIII: Relevance to inhibitor formation

2010 ◽  
Vol 104 (12) ◽  
pp. 1093-1098 ◽  
Author(s):  
Ana-Maria Navarrete ◽  
Suryasarathi Dasgupta ◽  
Maud Teyssandier ◽  
Yohann Repessé ◽  
Sandrine Delignat ◽  
...  
Keyword(s):  
Immune System ◽  
Factor Viii ◽  
Patient Management ◽  
Antigen Presenting Cells ◽  
Critical Issue ◽  
Haemophilia A ◽  
Antigen Presenting

SummaryThe immunogenicity of therapeutic factor VIII (FVIII) in patients with haemophilia A remains a critical issue in patient management. This review describes the immunological processes involved in the activation of the immune system against FVIII, with a particular focus on the role of endocytic receptors for the recognition of FVIII by antigen-presenting cells.

scholarly journals Novel tumour antigens and the development of optimal vaccine design

2018 ◽  
Vol 6 (2) ◽  
pp. 31-47 ◽  
Author(s):  
Victoria A Brentville ◽  
Suha Atabani ◽  
Katherine Cook ◽  
Lindy G Durrant
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Checkpoint Inhibitors ◽  
T Cell Responses ◽  
Tumour Cells ◽  
Great Promise ◽  
Cell Responses ◽  
Tumour Antigens

The interplay between tumours and the immune system has long been known to involve complex interactions between tumour cells, immune cells and the tumour microenvironment. The progress of checkpoint inhibitors in the clinic in the last decade has highlighted again the role of the immune system in the fight against cancer. Numerous efforts have been undertaken to develop ways of stimulating the cellular immune response to eradicate tumours. These interventions include the identification of appropriate tumour antigens as targets for therapy. In this review, we summarize progress in selection of target tumour antigen. Targeting self antigens has the problem of thymic deletion of high-affinity T-cell responses leaving a diminished repertoire of low-affinity T cells that fail to kill tumour cells. Thymic regulation appears to be less stringent for differentiation of cancer–testis antigens, as many tumour rejection antigens fall into this category. More recently, targeting neo-epitopes or post-translational modifications such as a phosphorylation or stress-induced citrullination has shown great promise in preclinical studies. Of particular interest is that the responses can be mediated by both CD4 and CD8 T cells. Previous vaccines have targeted CD8 T-cell responses but more recently, the central role of CD4 T cells in orchestrating inflammation within tumours and also differentiating into potent killer cells has been recognized. The design of vaccines to induce such immune responses is discussed herein. Liposomally encoded ribonucleic acid (RNA), targeted deoxyribonucleic acid (DNA) or long peptides linked to toll-like receptor (TLR) adjuvants are the most promising new vaccine approaches. These exciting new approaches suggest that the ‘Holy Grail’ of a simple nontoxic cancer vaccine may be on the horizon. A major hurdle in tumour therapy is also to overcome the suppressive tumour environment. We address current progress in combination therapies and suggest that these are likely to show the most promise for the future.

scholarly journals KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Albert Vallejo-Gracia ◽  
Daniel Sastre ◽  
Magalí Colomer-Molera ◽  
Laura Solé ◽  
María Navarro-Pérez ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Immunological Synapse ◽  
Physiological Role ◽  
Regulatory Subunit ◽  
Voltage Dependent ◽  
Functional Consequences ◽  
System Physiology ◽  
Antigen Presenting

AbstractThe voltage-dependent potassium channel Kv1.3 plays essential roles in the immune system, participating in leukocyte activation, proliferation and apoptosis. The regulatory subunit KCNE4 acts as an ancillary peptide of Kv1.3, modulates K+ currents and controls channel abundance at the cell surface. KCNE4-dependent regulation of the oligomeric complex fine-tunes the physiological role of Kv1.3. Thus, KCNE4 is crucial for Ca2+-dependent Kv1.3-related leukocyte functions. To better understand the role of KCNE4 in the regulation of the immune system, we manipulated its expression in various leukocyte cell lines. Jurkat T lymphocytes exhibit low KCNE4 levels, whereas CY15 dendritic cells, a model of professional antigen-presenting cells, robustly express KCNE4. When the cellular KCNE4 abundance was increased in T cells, the interaction between KCNE4 and Kv1.3 affected important T cell physiological features, such as channel rearrangement in the immunological synapse, cell growth, apoptosis and activation, as indicated by decreased IL-2 production. Conversely, ablation of KCNE4 in dendritic cells augmented proliferation. Furthermore, the LPS-dependent activation of CY15 cells, which induced Kv1.3 but not KCNE4, increased the Kv1.3-KCNE4 ratio and increased the expression of free Kv1.3 without KCNE4 interaction. Our results demonstrate that KCNE4 is a pivotal regulator of the Kv1.3 channelosome, which fine-tunes immune system physiology by modulating Kv1.3-associated leukocyte functions.

scholarly journals The Role of Trogocytosis in the Modulation of Immune Cell Functions

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1255
Author(s):  
Kensuke Miyake ◽  
Hajime Karasuyama
Keyword(s):  
Immune Cells ◽  
Immune Modulation ◽  
Immune Cell ◽  
Mhc Molecules ◽  
Cell Functions ◽  
Cell Extracts ◽  
Ligand Interactions ◽  
Molecule Interactions ◽  
Antigen Presenting

Trogocytosis is an active process, in which one cell extracts the cell fragment from another cell, leading to the transfer of cell surface molecules, together with membrane fragments. Recent reports have revealed that trogocytosis can modulate various biological responses, including adaptive and innate immune responses and homeostatic responses. Trogocytosis is evolutionally conserved from protozoan parasites to eukaryotic cells. In some cases, trogocytosis results in cell death, which is utilized as a mechanism for antibody-dependent cytotoxicity (ADCC). In other cases, trogocytosis-mediated intercellular protein transfer leads to both the acquisition of novel functions in recipient cells and the loss of cellular functions in donor cells. Trogocytosis in immune cells is typically mediated by receptor–ligand interactions, including TCR–MHC interactions and Fcγ receptor-antibody-bound molecule interactions. Additionally, trogocytosis mediates the transfer of MHC molecules to various immune and non-immune cells, which confers antigen-presenting activity on non-professional antigen-presenting cells. In this review, we summarize the recent advances in our understanding of the role of trogocytosis in immune modulation.

scholarly journals Impact of transfusion of blood components on the recipient immune system

2021 ◽  
Vol 23 (6) ◽  
pp. 1307-1318
Author(s):  
T. V. Glazanova ◽  
E. R. Shilova ◽  
A. V. Chechetkin ◽  
L. N. Bubnova
Keyword(s):  
Immune System ◽  
Immune Modulation ◽  
Hla Antigens ◽  
Perioperative Period ◽  
Blood Component ◽  
Malignant Neoplasms ◽  
Blood Components ◽  
Transfusion Therapy ◽  
Storage Lesion

Transfusions of blood provide essential therapeutic measures in a number of pathological conditions. However, when carrying out blood component therapy, it is important to consider probability of post-transfusion complications. Most of them are immune-mediated side effects. The unfavorable consequences of blood transfusions can manifest at long-range time periods, and pathogenesis of these phenomena may be associated not only with the presence of alloantibodies. They may be caused by alloimmunization to HLA antigens, leukocyte factors, including cytokines, products of leukocyte degranulation, as well as storage-related erythrocyte damage («storage lesion»), immunomodulatory properties of extracellular vesicles or microparticles derived from blood components, and other factors. Despite significant number of publications on this issue, a lot of unresolved issues still remain, concerning transfusion-related effects of blood components on the immune system of recipients. The review article provides the results of current studies in this area. We present and discuss the results of current studies and the features of transfusion-mediated immunomodulation (TRIM) revealed over recent years, when transfusing different blood components. The role of plasma factors, microparticles, platelets and erythrocytes, HLA sensitization and microchimerism in the development of TRIM is highlighted, the data on occurrence and clinical features of TRIM in perioperative period are presented. A separate section of the review provides information about recent clinical studies, devoted to the issues of TRIM in different clinical cohorts, including newborns, patients with malignant neoplasms, immunocompromised patients after heart and vascular surgery. The data on TRIM incidence in the patients with exhausted immune system due to previous disease or treatment, severe comorbidity, extensive surgical thoracic/abdominal intervention and artificial circulation are also in scope. As based on the studies performed, the role of distinct measures, e.g., washing of erythrocyte concentrates, leukodepletion, and gamma irradiation are discussed in view of potential TRIM prevention. The results of published research do not allow us to draw definite conclusions about the effects of blood component transfusion on the immune system of recipients with respect to differences between the studied groups of patients, characteristics of the studied disorders and clinical situations, diversity of hemocomponents, as well as varying standards of transfusion therapy adopted in different countries. However, the systematic literature review may provide some guidance in transfusion-mediated immune modulation.

scholarly journals New insights suggesting a possible role of a heat shock protein 70-kD family-related protein in antigen processing/presentation phenomenon in humans

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2865-2871 ◽  
Author(s):  
GC Manara ◽  
P Sansoni ◽  
L Badiali-De Giorgi ◽  
G Gallinella ◽  
C Ferrari ◽  
...  
Keyword(s):  
Cell Surface ◽  
Antigen Processing ◽  
Potential Role ◽  
Related Protein ◽  
Functional Studies ◽  
Recall Antigen ◽  
Normal Human ◽  
Antigen Presenting ◽  
Antigen Processing And Presentation

Abstract A possible role of the peptide binding protein (PBP) 72/74 in antigen processing and presentation has been recently suggested in mice. In order to evaluate a possible analogous role of a PBP72/74-related protein in humans, immunoelectron microscope investigations, functional studies, and immunofluorescence analyses were performed on normal human peripheral antigen-presenting cells. We demonstrated that the determinant recognized by antiheat shock protein (HSP) 72/73 monoclonal antibody (MoAb) is constitutively expressed on the cell surface of monocytes as well as of B cells. Moreover, the capability of monocytes to present a recall antigen to T cells was significantly decreased when preincubated with an anti-HSP72/73 MoAb. These data add further strength to a potential role of a protein related to human PBP72/74 homologue in antigen processing and/or presentation. Finally, the capability of anti-HSP72/73 MoAb to impair the ability of fixed monocytes to present a synthetic peptide demonstrates that cell surface- localized PBP72/74-related protein could play a role in antigen presentation.

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