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An Introduction to the Immune System and Vaccines
Published in Patricia G. Melloy, Viruses and Society, 2023
In the human body, we have two major branches to the immune system, the innate branch and the adaptive (acquired) branch. The two branches can communicate. Scientists refer to the two aspects of adaptive immune response as humoral immunity (older term referring to bodily fluids) and cell-mediated immunity. Humoral immunity involves two kinds of white blood cells: the B cells that make antibodies and the T cells that are responsible for cell-mediated immunity. Many good reviews or books of the immune system are available (Lostroh 2019; Coico and Sunshine 2015; Nicholson 2016; Marshall et al. 2018; Chaplin 2010).
The Inducible Defense System: The Induction and Development of the Inducible Defence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Michael A. Hickey, Diane Wallace Taylor
Each B and T cell expresses an antigen-specific receptor on its surface that allows it to interact with a single epitope on an antigen. The receptor on B cells is called the B cell receptor (BcR). This receptor, which was discussed in the previous chapter, is made up of a membrane-bound antibody molecule which is associated with two transmembrane proteins, Igα and Igβ (Figure 8.2). The B cell receptor directly binds to epitopes expressed on antigens that can be made up of proteins, carbohydrates, lipids, as well as many organic compounds.
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
B cells are a fundamental component of the body’s immune system. However, like most cells in the body, B cells can become cancerous leading to such diseases as non-Hodgkin’s lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). Targeting B-cell surface antigens that are highly expressed in B-cell malignancies with monoclonal antibodies is an ideal treatment strategy as both the B cells and antibodies can come into immediate contact in the bloodstream, and the antibodies can be designed to be highly specific for the individual surface antigens. Antibodies have been developed for several surface antigens including the “cluster of differentiation” or “CD” glycoproteins, found primarily on the surface of B cells (Figure 7.10). Examples include CD20 (targeted by ofatumumab and rituximab) and CD52 (targeted by alemtuzumab). B-lymphocyte surface antigens have also been targeted by Antibody-Drug Conjugates (ADCs) such as ibritumomab tiuxetan and tositumomab (i.e., CD20), brentuximab vedotin (i.e., CD30), and gemtuzumab ozogamicin (i.e., CD33) (see Section 7.3). As discussed above, interaction of the naked antibodies described in this section with their corresponding antigens can lead to cell death through both the ADCC and CDC effects, and also a direct apoptotic effect.
Current therapies for chronic lymphocytic leukemia: risk and prophylaxis strategies for secondary/opportunistic infections
Published in Expert Review of Hematology, 2023
Lucia Diella, Davide Fiore Bavaro, Giacomo Loseto, Crescenza Pasciolla, Carla Minoia, Daniela Di Gennaro, Alessandra Belati, Maria Stella De Candia, Francesco Di Gennaro, Annalisa Saracino, Attilio Guarini
At the initial presentation patients with CLL are often asymptomatic, but in some cases B symptoms can occur, such as fever for more than two weeks with no evidence of infection, unintentional weight loss (more than 10% of body weight over the last six months), drenching night sweats with no evidence of infection, extreme fatigue and early satiety [3]. Another important concern of CLL is the impairment of both innate and adaptative immunity, leading to a condition of immune dysregulation, independently from therapies. Indeed, B-CLL cells impairment affect the activity of innate immunity cells, including macrophages, dendritic cells, neutrophils and natural killers, resulting in tolerance toward neoplastic cells and increased infection risk [4]. Nevertheless, even adaptative immunity disruption is expected in course of CLL, regarding T and B cells activity. In particular, upregulation of PD-1 on T cell (CD4+ and CD8+) is observed in CLL, and is associated with higher incidence of infectious complication, regardless of other prognostic factors [5]. Finally, lack of functional B cells decreases the ability to produce antibodies for immune responses, resulting in hypogammaglobinemia, which eventually leads to an increased risk of infection, even in early stage of disease [6].
Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group
Published in Amyloid, 2023
Ashutosh D. Wechalekar, M. Teresa Cibeira, Simon D. Gibbs, Arnaud Jaccard, Shaji Kumar, Giampaolo Merlini, Giovanni Palladini, Vaishali Sanchorawala, Stefan Schönland, Christopher Venner, Mario Boccadoro, Efstathios Kastritis
The B-cell maturation antigen (BCMA) is another cell surface molecule ubiquitously expressed on plasma cell as well as their B-cell progenitors. There have been several unique targeting strategies demonstrating clear anti-plasma cell activity in multiple myeloma [82]. To date, however, the experience specifically in AL amyloidosis is limited. A novel antibody-drug conjugate, Belantamab mafodotin, combines the potent mafodotin toxin with plasma cell targeting anti-BCMA monoclonal antibody [83]. It has demonstrated excellent single agent activity in advanced relapsed and refractory multiple myeloma. Combination studies with various immunomodulating agents and proteasome inhibitors are ongoing. A prospective EMN study (NCT04617925) is examining Belantamab in relapsed AL amyloidosis. An important consideration with this agent is the unique ocular toxicity in the form of keratopathy which has proven to be a challenge in the delivery of this agent. In AL amyloidosis, with the often-lower clonal burden, less frequent and finite dosing strategies built around response adapted approaches may help limit this issue without compromising efficacy.
HSC70 is a novel binding partner involved in the capture of immunoglobulins on B cells in the NOD mouse
Published in Autoimmunity, 2022
Emma Renman, Rifat Ekici, Mia Sundström, Kristina Lejon
B cells are essential in the humoral immune defense with a prime role to secrete antibodies that are distributed peripherally in order to neutralise and opsonise foreign antigens. In addition, the B cell subtypes follicular B cells and, in particular, marginal zone B cells can capture and transport antigen-immunoglobulin immune complexes (ICs) through surface expression of complement receptors [1,2]. Marginal zone B cells can further shuttle between the marginal zone and follicles in the spleen [3] and deliver ICs to follicular dendritic cells for further activation of the immune system [1]. Studies have also shown that B cells are involved in the endocytosis of foreign antigen-antibody complexes through an Fc(αμ)R-dependent mechanism [4] and activated B cells can through membrane transfer share their B cell receptors with bystander B cells [5]. Thus, the role of B cells in the immune system is undoubtedly versatile and indispensable for a balanced immune homeostasis.