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Frontiers in Immunology 2022infection causes the most severe form of malaria. It has been hypothesized that directly suppresses host immune responses because sufficient acquired immunity is often... (Review)
Review
infection causes the most severe form of malaria. It has been hypothesized that directly suppresses host immune responses because sufficient acquired immunity is often not induced even by repeated infections in malaria-endemic areas. It is known that many kinds of -derived proteins are expressed on the surface of -infected erythrocytes (IEs), and these proteins have long been thought to be a key to the elucidation of the host immune evasion mechanisms. Our recent studies have revealed that the -derived erythrocyte surface antigen, RIFIN, the largest multiple gene family protein in the genome, suppresses host immune cell activation through direct interaction with human inhibitory immune receptors. In this review, we will discuss the molecular mechanisms for host immune evasion by -infected erythrocyte surface antigens. In addition, we will discuss the recently identified host immune response to using specialized antibodies that target host--derived molecule interactions.
Topics: Antigens, Protozoan; Antigens, Surface; Erythrocytes; Humans; Immune Evasion; Malaria; Malaria, Falciparum; Plasmodium falciparum; Protozoan Proteins
PubMed: 35784341
DOI: 10.3389/fimmu.2022.901864 -
International Journal of Molecular... Nov 2021Theranostics, a combination of therapy and diagnostics, is a field of personalized medicine involving the use of the same or similar radiopharmaceutical agents for the... (Review)
Review
Theranostics, a combination of therapy and diagnostics, is a field of personalized medicine involving the use of the same or similar radiopharmaceutical agents for the diagnosis and treatment of patients. Prostate-specific membrane antigen (PSMA) is a promising theranostic target for the treatment of prostate cancers. Diagnostic PSMA radiopharmaceuticals are currently used for staging and diagnosis of prostate cancers, and imaging can predict response to therapeutic PSMA radiopharmaceuticals. While mainly used in the setting of metastatic, castrate-resistant disease, clinical trials are investigating the use of PSMA-based therapy at earlier stages, including in hormone-sensitive or hormone-naïve prostate cancers, and in oligometastatic prostate cancers. This review explores the use of PSMA as a theranostic target and investigates the potential use of PSMA in earlier stage disease, including hormone-sensitive metastatic prostate cancer, and oligometastatic prostate cancer.
Topics: Antigens, Surface; Glutamate Carboxypeptidase II; Humans; Male; Neoplasm Metastasis; Precision Medicine; Prostate; Prostatic Neoplasms; Radiopharmaceuticals; Theranostic Nanomedicine
PubMed: 34829977
DOI: 10.3390/ijms222212095 -
ACS Chemical Biology Dec 2022Glycans attached to glycoproteins can contribute to stability, mediate interactions with other proteins, and initiate signal transduction. Glycan conformation, which is...
Glycans attached to glycoproteins can contribute to stability, mediate interactions with other proteins, and initiate signal transduction. Glycan conformation, which is critical to these processes, is highly variable and often depicted as sampling a multitude of conformers. These conformers can be generated by molecular dynamics simulations, and more inclusively by accelerated molecular dynamics, as well as other extended sampling methods. However, experimental assessments of the contribution that various conformers make to a native ensemble are rare. Here, we use long-range pseudo-contact shifts (PCSs) of NMR resonances from an isotopically labeled glycoprotein to identify preferred conformations of its glycans. The -terminal domain from human Carcinoembryonic Antigen Cell Adhesion Molecule 1, hCEACAM1-Ig1, was used as the model glycoprotein in this study. It has been engineered to include a lanthanide-ion-binding loop that generates PCSs, as well as a homogeneous set of three C-labeled -glycans. Analysis of the PCSs indicates that preferred glycan conformers have extensive contacts with the protein surface. Factors leading to this preference appear to include interactions between -acetyl methyls of GlcNAc residues and hydrophobic surface pockets on the protein surface.
Topics: Humans; Antigens, CD; Cell Adhesion Molecules; Glycoproteins; Polysaccharides; Protein Conformation
PubMed: 36417668
DOI: 10.1021/acschembio.2c00714 -
Journal of Biosciences 2020The hallmarks of the adaptive immune response are specificity and memory. The cellular response is mediated by T cells which express cell surface T cell receptors (TCRs)... (Review)
Review
The hallmarks of the adaptive immune response are specificity and memory. The cellular response is mediated by T cells which express cell surface T cell receptors (TCRs) that recognize peptide antigens in complex with major histocompatibility complex (MHC) molecules on antigen presenting cells (APCs). However, binding of cognate TCRs with MHC-peptide complexes alone (signal 1) does not trigger optimal T cell activation. In addition to signal 1, the binding of positive and negative costimulatory receptors to their ligands modulates T cell activation. This complex signaling network prevents aberrant activation of T cells. CD28 is the main positive costimulatory receptor on naı¨ve T cells; upon activation, CTLA4 is induced but reduces T cell activation. Further studies led to the identification of additional negative costimulatory receptors known as checkpoints, e.g. PD1. This review chronicles the basic studies in T cell costimulation that led to the discovery of checkpoint inhibitors, i.e. antibodies to negative costimulatory receptors (e.g. CTLA4 and PD1) which reduce tumor growth. This discovery has been recognized with the award of the 2018 Nobel prize in Physiology/Medicine. This review highlights the structural and functional roles of costimulatory receptors, the mechanisms by which checkpoint inhibitors work, the challenges encountered and future prospects.
Topics: Antigen-Presenting Cells; CD28 Antigens; CTLA-4 Antigen; Costimulatory and Inhibitory T-Cell Receptors; Humans; Immune Checkpoint Inhibitors; Lymphocyte Activation; Neoplasms; Programmed Cell Death 1 Receptor; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 32345776
DOI: No ID Found -
Protein Science : a Publication of the... Sep 2021T-cell co-stimulation through CD28/CTLA4:B7-1/B7-2 axis is one of the extensively studied pathways that resulted in the discovery of several FDA-approved drugs for...
T-cell co-stimulation through CD28/CTLA4:B7-1/B7-2 axis is one of the extensively studied pathways that resulted in the discovery of several FDA-approved drugs for autoimmunity and cancer. However, many aspects of the signaling mechanism remain elusive, including oligomeric association and clustering of B7-2 on the cell surface. Here, we describe the structure of the IgV domain of B7-2 and its cryptic association into 1D arrays that appear to represent the pre-signaling state of B7-2 on the cell membrane. Super-resolution microscopy experiments on heterologous cells expressing B7-2 and B7-1 suggest, B7-2 form relatively elongated and larger clusters compared to B7-1. The sequence and structural comparison of other B7 family members, B7-1:CTLA4 and B7-2:CTLA-4 complex structures, support our view that the observed B7-2 1D zipper array is physiologically important. This observed 1D zipper-like array also provides an explanation for its clustering, and upright orientation on the cell surface, and avoidance of spurious signaling.
Topics: Amino Acid Sequence; Animals; B7-1 Antigen; B7-2 Antigen; Binding Sites; CD28 Antigens; CTLA-4 Antigen; Cell Line, Tumor; Gene Expression; Humans; Mice; Models, Molecular; Neurons; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protein Multimerization; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid
PubMed: 34191384
DOI: 10.1002/pro.4151 -
The Journal of Veterinary Medical... Apr 2022Understanding the immune dynamics in the respiratory mucosa of calves is necessary for a good management of bovine respiratory disease. Immune dynamics in the...
Understanding the immune dynamics in the respiratory mucosa of calves is necessary for a good management of bovine respiratory disease. Immune dynamics in the respiratory mucosa in humans and experimental animals has been assessed by flow cytometric analysis of bronchoalveolar lavage fluid (BALF); however, few reports have addressed this subject in calves. The aim of this study was to establish a universal method to analyze bronchoalveolar lavage fluid (BALF) by flow cytometry and to obtain basic knowledge of bovine respiratory mucosal immune dynamics. We investigated the immune cell populations in BALF and evaluated the surface antigen expression of alveolar macrophages in calves using flow cytometer. To further analyze the surface antigen variation observed in alveolar macrophages in detail, stimulation assays were performed in vitro. BALF cells were separated into three distinct populations based on their light scatter plot, which were considered to be macrophages, lymphocytes, and neutrophils. In most individuals, most of the BALF immune cells were alveolar macrophages, but an increased proportion of lymphocytes and neutrophils was observed in some individuals. Analysis of each surface antigen expression in alveolar macrophages showed that CD21 and MHC class II expression changed in response to changes in the leukocyte population. Moreover, when alveolar macrophages were stimulated with interferon-γ in vitro, the expression of CD21 was drastically reduced and MHC class II was increased, suggesting that functional changes in alveolar macrophages themselves are involved in the immune dynamics.
Topics: Animals; Antigens, Surface; Bronchoalveolar Lavage Fluid; Cattle; Cattle Diseases; Flow Cytometry; Macrophages, Alveolar; Respiratory Mucosa
PubMed: 35153256
DOI: 10.1292/jvms.21-0522 -
Journal of Epidemiology and Global... Dec 2022Estimating the prevalence of infectious diseases, including viral hepatitis, among refugees is important for evaluating their health needs and predicting the burden on...
BACKGROUND
Estimating the prevalence of infectious diseases, including viral hepatitis, among refugees is important for evaluating their health needs and predicting the burden on the health system of the host country. This study aimed at estimating the seroprevalence of viral hepatitis among refugees in Egypt.
METHODS
This cross-sectional study involved a heterogeneous group of 501 refugees. Enzyme-linked immunosorbent assays were used to detect IgG antibodies against hepatitis A virus (HAV), B virus (HBV) surface antigen (anti-HBsAg), C virus (HCV), and HBV surface antigen (HBsAg).
RESULTS
Anti-HAV was the most prevalent marker (n = 482, 96.2%), followed by anti-HBs (n = 142, 28.3%) and HBsAg (n = 21, 4.2%), while only four refugees (0.8%) had positive anti-HCV IgG. Anti-HBs was higher in males (p < 0.05). Older refugees and non-working subjects had significantly higher seropositive rates of anti-HAV (p = 0.051 and p = 0.023, respectively), while students and those below 15 years of age had higher rates of anti-HBs (p < 0.05). Positive HBsAg results were associated with history of hepatitis (p < 0.001). Obese participants were more likely to be positive for HBsAg (p = 0.025) and anti-HBs (p < 0.05). Sudanese refugees had significantly higher rates of anti-HAV antibodies (p = 0.049), while Yemini refugees had significantly higher rates for HBsAg (p = 0.019) positivity. Residents of Dakahlia had significantly higher rates of anti-HAV (p = 0.008) and anti-HBs (p < 0.05). None of the studied risk factors was significantly associated with anti-HCV.
CONCLUSION
Refugees in Egypt have poor immunity against HBV with intermediate to high HBV and low HCV prevalence rates. Despite that 65% of refugees received the HAV vaccine, almost all had IgG anti-HAV, denoting previous infection.
Topics: Humans; Male; Antigens, Surface; Cross-Sectional Studies; Egypt; Hepatitis A; Hepatitis A Antibodies; Hepatitis B Antibodies; Hepatitis, Viral, Human; Immunoglobulin G; Refugees; Seroepidemiologic Studies; Hepatitis B; Hepatitis C
PubMed: 36107333
DOI: 10.1007/s44197-022-00060-6 -
PloS One 2022Myelodysplastic syndrome (MDS) is a heterogeneous hematopoietic stem cell disorder with thrombocytopenia. Flow cytometric immunophenotyping of blood cells has been...
OBJECTIVES
Myelodysplastic syndrome (MDS) is a heterogeneous hematopoietic stem cell disorder with thrombocytopenia. Flow cytometric immunophenotyping of blood cells has been instrumental in diagnosis as co-criteria, but the data regarding platelets remains lacking. This study aims to determine if there is a difference in surface antigen levels on platelets by comparing surface antigen levels in MDS patients and healthy control subjects. Concurrently, as flow cytometric gating can reveal the diameter of cells, this study will investigate differences in giant platelet percentage by comparing these percentages in high- and low-risk MDS patients.
STUDY DESIGN
Twenty newly diagnosed MDS patients were enrolled in this study. Platelet surface antigen levels were determined by measuring the binding capacity of antibodies with flow cytometry.
RESULTS
Platelets of MDS patients were shown to have a lower level of CD61 and higher levels of CD31 and CD36 than healthy controls. Judged by forward scatter (FSC), MDS patients' platelets appeared to be larger than those of healthy control subjects, whereas the MFI adjusted by diameter (MFI/FSC ratio) of CD31, CD41a, CD42a, CD42b and CD61 on platelets were lower in MDS patients than in healthy control subjects. There was a significant quantity of giant platelets found in MDS patients, and the high-risk MDS patients tended to have a higher percentage of giant platelets than low-risk patients. Conclusions: All the results indicate that MDS patients exhibit a lower antigen presentation (MFI) adjusted by diameter on platelets than healthy controls and the giant platelets detected by flow cytometry might correlate with the condition of MDS.
Topics: Humans; Immunophenotyping; Blood Platelets; Pilot Projects; Myelodysplastic Syndromes; Antigens, Human Platelet; Antigens, Surface
PubMed: 36409726
DOI: 10.1371/journal.pone.0278040 -
BMJ Open May 2021The association between ABO blood group and risk of liver cancer is unclear, although few studies have reported positive results. This study examined the relationship...
OBJECTIVE
The association between ABO blood group and risk of liver cancer is unclear, although few studies have reported positive results. This study examined the relationship between ABO blood group and liver cancer in hepatitis B surface antigen (HBsAg)-positive individuals.
DESIGN
A high-risk population-based cohort study.
SETTING
The study was started in 2007 and closed in 2019; the number of observed person-years as obtained by ABO blood group.
PARTICIPANTS
The study included 3663 individuals with positive HBsAg, including men aged 30-70 and women aged 40-70.
OUTCOME MEASURES
The frequencies of ABO group in the cohort population and patients with liver cancer were calculated, respectively. χ test was used to compare differences, and the relative risk (95% CI) for development of liver cancer was evaluated.
RESULTS
The frequency distribution of blood types A, B, O and AB was 1118 (30.52%), 1073 (29.29%), 1104 (30.14%) and 368 (10.05%), respectively, among 3663 cohort individuals. In the cohort, patients with liver cancer (n=336) were of the following frequencies: type A: 104 (30.95%); type B: 97 (28.87%); type O: 95 (28.27%); and type AB: 40 (11.90%). No significant difference was found between patients with liver cancer and other individuals. The annual incidence rate of liver cancer was 906.34 per 100 000 person-years, and for blood type A, B, O and AB the rates were 917.76, 893.78, 846.02 and 1093.43 per 100 000 person-years, respectively. The relative risk (95% CI) was 0.97 (0.74 to 1.29), 0.92 (0.70 to 1.22) and 1.19 (0.82 to 1.72) for blood types B, O and AB, respectively, compared with blood type A.
CONCLUSION
There were no significant differences in the frequency distribution of ABO blood groups in patients with liver cancer within this high-risk cohort, which demonstrates lack of positive association between ABO blood group and risk of liver cancer.
Topics: ABO Blood-Group System; Cohort Studies; Female; Hepatitis B Surface Antigens; Humans; Liver Neoplasms; Male; Prospective Studies; Risk Factors
PubMed: 33980521
DOI: 10.1136/bmjopen-2020-044039 -
Science China. Life Sciences Oct 2023Monkeypox was declared a global health emergency by the World Health Organization, and as of March 2023, 86,000 confirmed cases and 111 deaths across 110 countries have...
Monkeypox was declared a global health emergency by the World Health Organization, and as of March 2023, 86,000 confirmed cases and 111 deaths across 110 countries have been reported. Its causal agent, monkeypox virus (MPV) belongs to a large family of double-stranded DNA viruses, Orthopoxviridae, that also includes vaccinia virus (VACV) and others. MPV produces two distinct forms of viral particles during its replication cycles: the enveloped viron (EV) that is released via exocytosis, and the mature viron (MV) that is discharged through lysis of host cells. This study was designed to develop multi-valent mRNA vaccines against monkeypox EV and MV surface proteins, and examine their efficacy and mechanism of action. Four mRNA vaccines were produced with different combinations of surface proteins from EV (A35R and B6R), MV (A29L, E8L, H3L and M1R), or EV and MV, and were administered in Balb/c mice to assess their immunogenicity potentials. A dynamic immune response was observed as soon as seven days after initial immunization, while a strong IgG response to all immunogens was detected with ELISA after two vaccinations. The higher number of immunogens contributed to a more robust total IgG response and correlating neutralizing activity against VACV, indicating the additive potential of each immunogen in generating immune response and nullifying VACV infection. Further, the mRNA vaccines elicited an antigen-specific CD4 T cell response that is biased towards Th1. The mRNA vaccines with different combinations of EV and MV surface antigens protected a mouse model from a lethal dose VACV challenge, with the EV and MV antigens-combined vaccine offering the strongest protection. These findings provide insight into the protective mechanism of multi-valent mRNA vaccines against MPV, and also the foundation for further development of effective and safe mRNA vaccines for enhanced protection against monkeypox virus outbreak.
Topics: Animals; Mice; Mpox (monkeypox); Antigens, Surface; Vaccinia virus; Membrane Proteins; Immunity; Immunoglobulin G; Antibodies, Viral
PubMed: 37300753
DOI: 10.1007/s11427-023-2378-x