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The New England Journal of Medicine Feb 2023
Review
Topics: Humans; Acute-Phase Proteins; Immunity, Humoral; Immunity, Innate
PubMed: 36724330
DOI: 10.1056/NEJMra2206346 -
Frontiers in Immunology 2022Since the onset of the COVID-19 pandemic, the medical field has been forced to apply the basic knowledge of immunology with the most up-to-date SARS-CoV-2 findings and... (Review)
Review
Since the onset of the COVID-19 pandemic, the medical field has been forced to apply the basic knowledge of immunology with the most up-to-date SARS-CoV-2 findings and translate it to the population of the whole world in record time. Following the infection with the viral antigen, adaptive immune responses are activated mainly by viral particle encounters with the antigen-presenting cells or B cell receptors, which induce further biological interactions to defend the host against the virus. After the infection has been warded off, the immunological memory is developed. The SARS-CoV cellular immunity has been shown to persist even 17 years after the infection, despite the undetectable humoral component. Similar has been demonstrated for the SARS-CoV-2 T cell memory in a shorter period by assessing interferon-gamma levels when heparinized blood is stimulated with the virus-specific peptides. T cells also play an irreplaceable part in a humoral immune reaction as the backbone of a cellular immune response. They both provide the signals for B cell activation and the maturation, competence, and memory of the humoral response. B cell production of IgA was shown to be of significant influence in mediating mucosal immunity as the first part of the defense mechanism and in the development of nasal vaccines. Here, we interpret the recent SARS-CoV-2 available research, which encompasses the significance and the current understanding of adaptive immune activity, and compare it among naive, exposed, and vaccinated blood donors. Our recent data showed that those who recovered from COVID-19 and those who are vaccinated with EMA-approved vaccines had a long-lasting cellular immunity. Additionally, we analyze the humoral responses in immunocompromised patients and memory mediated by cellular immunity and the impact of clonality in the SARS-CoV-2 pandemic regarding breakthrough infections and variants of concern, both B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants.
Topics: COVID-19; COVID-19 Vaccines; Humans; Immunity, Humoral; Pandemics; SARS-CoV-2; Vaccination
PubMed: 35603211
DOI: 10.3389/fimmu.2022.848582 -
Journal of Pharmaceutical Sciences Jan 2020Antibody-based proteins have become an important class of biologic therapeutics, due in large part to the stability, specificity, and adaptability of the antibody... (Review)
Review
Antibody-based proteins have become an important class of biologic therapeutics, due in large part to the stability, specificity, and adaptability of the antibody framework. Indeed, antibodies not only have the inherent ability to bind both antigens and endogenous immune receptors but also have proven extremely amenable to protein engineering. Thus, several derivatives of the monoclonal antibody format, including bispecific antibodies, antibody-drug conjugates, and antibody fragments, have demonstrated efficacy for treating human disease, particularly in the fields of immunology and oncology. Reviewed here are considerations for the design of antibody-based therapeutics, including immunological context, therapeutic mechanisms, and engineering strategies. First, characteristics of antibodies are introduced, with emphasis on structural domains, functionally important receptors, isotypic and allotypic differences, and modifications such as glycosylation. Then, aspects of therapeutic antibody design are discussed, including identification of antigen-specific variable regions, choice of expression system, use of multispecific formats, and design of antibody derivatives based on fragmentation, oligomerization, or conjugation to other functional moieties. Finally, strategies to enhance antibody function through protein engineering are reviewed while highlighting the impact of fundamental biophysical properties on protein developability.
Topics: Animals; Antibodies, Monoclonal; Communicable Diseases; Drug Design; Humans; Immunity, Humoral; Immunoconjugates; Immunoglobulin G; Neoplasms; Protein Engineering; Receptors, Fc
PubMed: 31173761
DOI: 10.1016/j.xphs.2019.05.031 -
Nature Reviews. Immunology Mar 2015Humoral immunity depends on the germinal centre (GC) reaction during which somatically mutated high-affinity memory B cells and plasma cells are generated. Recent... (Review)
Review
Humoral immunity depends on the germinal centre (GC) reaction during which somatically mutated high-affinity memory B cells and plasma cells are generated. Recent studies have uncovered crucial cues that are required for the formation and the maintenance of GCs and for the selection of high-affinity antibody mutants. In addition, it is now clear that these events are promoted by the dynamic movements of cells within and between GCs. These findings have resolved the complexities of the GC reaction in greater detail than ever before. This Review focuses on these recent advances and discusses their implications for the establishment of humoral immunity.
Topics: Antibody Affinity; B-Lymphocytes; Germinal Center; Humans; Immunity, Humoral; Plasma Cells
PubMed: 25656706
DOI: 10.1038/nri3804 -
Nature Immunology Jul 2017Biologists, physicians and immunologists have contributed to the understanding of the cellular participants and biological pathways involved in inflammation. Here, we...
Biologists, physicians and immunologists have contributed to the understanding of the cellular participants and biological pathways involved in inflammation. Here, we provide a general guide to the cellular and humoral contributors to inflammation as well as to the pathways that characterize inflammation in specific organs and tissues.
Topics: Acute Disease; Chronic Disease; Communicable Diseases; Humans; Immunity, Cellular; Immunity, Humoral; Inflammation
PubMed: 28722720
DOI: 10.1038/ni.3790 -
The Journal of Experimental Medicine Jul 2023B cells develop from hematopoietic stem cells in the bone marrow. Once generated, they serve multiple roles in immune regulation and host defense. However, their most... (Review)
Review
B cells develop from hematopoietic stem cells in the bone marrow. Once generated, they serve multiple roles in immune regulation and host defense. However, their most important function is producing antibodies (Ab) that efficiently clear invading pathogens. This is achieved by generating memory B cells that rapidly respond to subsequent Ag exposure, and plasma cells (PCs) that continually secrete Ab. These B cell subsets maintain humoral immunity and host protection against recurrent infections for extended periods of time. Thus, the generation of antigen (Ag)-specific memory cells and PCs underlies long-lived serological immunity, contributing to the success of most vaccines. Our understanding of immunity is often derived from animal models. However, analysis of individuals with monogenic defects that disrupt immune cell function are unprecedented models to link genotypes to clinical phenotypes, establish mechanisms of disease pathogenesis, and elucidate critical pathways for immune cell development and differentiation. Here, we review fundamental breakthroughs in unraveling the complexities of humoral immunity in humans that have come from the discovery of inborn errors disrupting B cell function.
Topics: Animals; Humans; B-Lymphocytes; Plasma Cells; Cell Differentiation; Immunity, Humoral; B-Lymphocyte Subsets; Antibodies
PubMed: 37273190
DOI: 10.1084/jem.20221105 -
Drug Discovery Today. Technologies Dec 2020Carbohydrate adjuvants are safe and biocompatible compounds usable as sustained delivery systems and stimulants of ongoing humoral and cellular immune responses, being... (Review)
Review
Carbohydrate adjuvants are safe and biocompatible compounds usable as sustained delivery systems and stimulants of ongoing humoral and cellular immune responses, being especially suitable for the development of vaccines against intracellular pathogens where alum is useless. The development of new adjuvants is difficult and expensive, however, in the last two years, seven new carbohydrate-based adjuvants have been patented, also there are twelve ongoing clinical trials of vaccines that contain carbohydrate-based adjuvants, as well as numerous publications on their mechanism of action and safety. More research is necessary to improve the existent adjuvants and develop innovative ones.
Topics: Adjuvants, Immunologic; Animals; Carbohydrates; Clinical Trials as Topic; Drug Development; Drug Evaluation, Preclinical; Humans; Immunity, Cellular; Immunity, Humoral; Models, Animal; Vaccination
PubMed: 33388128
DOI: 10.1016/j.ddtec.2020.09.005 -
Immunity Oct 2022Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on...
Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on secondary challenges remain unclear. Here, using preclinical SARS-CoV and HIV mouse models, we demonstrated that the antibodies elicited during primary humoral responses shaped the naive B cell recruitment to GCs during secondary exposures. The antibodies from primary responses could either enhance or, conversely, restrict the GC participation of naive B cells: broad-binding, low-affinity, and low-titer antibodies enhanced recruitment, whereas, by contrast, the high titers of high-affinity, mono-epitope-specific antibodies attenuated cognate naive B cell recruitment. Thus, the directionality and intensity of that effect was determined by antibody concentration, affinity, and epitope specificity. Circulating antibodies can, therefore, be important determinants of antigen immunogenicity. Future vaccines may need to overcome-or could, alternatively, leverage-the effects of circulating primary antibodies on subsequent naive B cell recruitment.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Antigens; B-Lymphocytes; Epitopes; Germinal Center; Immunity, Humoral; Mice
PubMed: 35987201
DOI: 10.1016/j.immuni.2022.07.020 -
Frontiers in Cellular and Infection... 2022Leishmaniasis presents different types of clinical manifestations that can be divided into cutaneous leishmaniasis and visceral leishmaniasis. The host's immune system,... (Review)
Review
Leishmaniasis presents different types of clinical manifestations that can be divided into cutaneous leishmaniasis and visceral leishmaniasis. The host's immune system, associated with genetic and nutritional factors, is strongly involved in the evolution of the disease or parasite escape. Humoral immunity is characterized by the production of antibodies capable of promoting neutralization, opsonization, and activation of the complement system. In this scenario, B lymphocytes produce antibodies that play an important role in Leishmania infection although neglected for a long time. Thus, relevant aspects in the establishment of Leishmania infection will be addressed, highlighting the importance of humoral immunity during the entire process of Leishmania infection.
Topics: Humans; Leishmaniasis; Leishmaniasis, Visceral; Leishmaniasis, Cutaneous; Immunity, Humoral; Antibodies
PubMed: 36579347
DOI: 10.3389/fcimb.2022.1063291 -
Oncoimmunology Mar 2021Pancreatic ductal adenocarcinoma (PDAC) has traditionally been thought of as an immunologically quiescent tumor type presumably because of a relatively low tumor...
Pancreatic ductal adenocarcinoma (PDAC) has traditionally been thought of as an immunologically quiescent tumor type presumably because of a relatively low tumor mutational burden (TMB) and poor responses to checkpoint blockade therapy. However, many PDAC tumors exhibit T cell inflamed phenotypes. The presence of tertiary lymphoid structures (TLS) has recently been shown to be predictive of checkpoint blockade response in melanomas and sarcomas, and are prognostic for survival in PDAC. In order to more comprehensively understand tumor immunity in PDAC patients with TLS, we performed RNA-seq, single and multiplex IHC, flow cytometry and predictive genomic analysis on treatment naïve, PDAC surgical specimens. Forty-six percent of tumors contained distinct T and B cell aggregates reflective of "early-stage TLS" (ES-TLS), which correlated with longer overall and progression-free survival. These tumors had greater CD8 T cell infiltration but were not defined by previously published TLS gene-expression signatures. ES-TLS tumors were enriched for IgG1 class-switched memory B cells and memory CD4 T cells, suggesting durable immunological memory persisted in these patients. We also observed the presence of active germinal centers (mature-TLS) in 31% of tumors with lymphocyte clusters, whose patients had long-term survival (median 56 months). M-TLS-positive tumors had equivalent overall T cell infiltration to ES-TLS, but were enriched for activated CD4 memory cells, naive B cells and NK cells. Finally, using a TCGA-PDAC dataset, ES-TLS tumors harbored a decreased TMB, but M-TLS with germinal centers expressed significantly more MHCI-restricted neoantigens as determined by an neoantigen prediction method. Interestingly, M-TLS tumors also had evidence of increased rates of B cell somatic hypermutation, suggesting that germinal centers form in the presence of high-quality tumor neoantigens leading to increased humoral immunity that confers improved survival for PDAC patients. TLS: tertiary lymphoid structures; GC: germinal center(s); PDAC: pancreatic ductal adenocarcinoma; RNA-seq: RNA sequencing; BCRseq: B cell receptor sequencing; HEV: high endothelial venule; PNAd: peripheral node addressin; TMB: tumor mutational burden; TCGA: the cancer genome atlas; PAAD: pancreatic adenocarcinoma; FFPE: formalin fixed paraffin embedded; TIME: tumor immune microenvironment.
Topics: Adenocarcinoma; Germinal Center; Humans; Immunity, Humoral; Pancreatic Neoplasms; Survivorship; Tertiary Lymphoid Structures; Tumor Microenvironment
PubMed: 33796412
DOI: 10.1080/2162402X.2021.1900635