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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).
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.
The immune and lymphatic systems, infection and sepsis
Published in Peate Ian, Dutton Helen, Acute Nursing Care, 2020
Michelle Treacy, Caroline Smales, Helen Dutton
B cells or B lymphocytes are responsible for humoral or antibody-mediated immunity and form part of the adaptive immune response. There are two types of B cell: Plasma cells, which produce antibodies; the primary response.Memory B cells, stored in lymph nodes, which remember pathogens, allowing a much faster response to a second or subsequent exposure to the pathogen; the secondary response (see Figure 12.7) (Colbert et al. 2012).
IgG4 related disease and aortitis: an up-to-date review
Published in Scandinavian Journal of Rheumatology, 2023
N Jayachamarajapura Onkaramurthy, SC Suresh, P Theetha Kariyanna, A Jayarangaiah, G Prakash, B Raju
Extensive evidence on the disease response to B-cell-depleting therapy confirms a major role of B cells in disease pathogenesis. Short-lived oligoclonal expanded antibody-producing cells with active B-cell surface antigens CD20−, CD19+, CD38+, and CD27+ identifying plasmablasts were increased in the peripheral blood of a patient with IgG4-RD (21). Extensive hypermutation in the hypervariable and framework region of immunoglobulin genes were found in the circulating plasmablasts (22). Furthermore, the levels of plasmablasts in the circulation are found to be correlated with the disease activity and organ involvement irrespective of serum IgG4 concentration, indicating a pathogenic significance (23, 24). Hence, plasmablasts may serve as a biomarker of disease activity, response to therapy, and relapse.
Memory B cells and long-lived plasma cells in AMR
Published in Renal Failure, 2022
Wenlong Yue, Jia Liu, Xiaohu Li, Luman Wang, Jinfeng Li
Plasma cells are differentiated from activated B cells. As the final B cells to be produced, plasma cells can be classified into short-lived plasma cells and long-lived plasma cells from GC [60]. Long-lived plasma cells produce high-affinity, class-switched antibodies, while memory B cells have broader antigen specificity. Therefore, when antigens enter the human body, long-lived plasma cells produce neutralizing antibodies against antigens in the first phase of immune response. In the second phase of immune response, memory B cells play important roles by rapidly producing antibodies with high affinity against various pathogens [50,55]. In terms of surface marker expression, CD38 and CD138 generally colocalize on the plasma cell surface [61]. Garimalla et al. [62] reported ASCs, including plasma cells and long-lived plasma cells, in peripheral blood 7 days after tetanus vaccination. These ASCs lacked CD20 expression. CD20 is specifically expressed in the late stage of B-cell development, and the failure to detect CD20 may be an indication of successful B- cell conversion into plasma cells [63,64]. After clinical transplantation, mature GC B cells and memory B cells can be eliminated from patients with AMR with drugs targeting CD20 (such as rituximab), but this treatment cannot effectively reduce the concentration of DSAs, which is consistent with the absence of CD20 molecules on the surface of plasma cells.
Does standard pharmacotherapy still have a major role in the treatment of aggressive B-cell malignancies?
Published in Expert Opinion on Pharmacotherapy, 2022
Dominika Kabiesz, Piotr Smolewski
Aggressive B-cell lymphomas comprise a heterogeneous group of malignancies that arise at different stages of B-cell development via various mechanisms of neoplastic transformation. The most common forms include diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), B lymphoblastic lymphoma (B-LBL), and mantle cell lymphoma (MCL) with its blastoid variant. The widely applicable standard regimen, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) provides effective treatment results in two-thirds of patients with the most frequently diagnosed lymphoma, DLBCL. Relapsed/refractory (R/R) patients have a poor prognosis, which necessitates the development of new treatment modalities. Despite the evolution of new biological therapies, including biologically targeted agents, novel monoclonal antibodies or chimeric antigen receptor T-cell therapy (CAR-T), standard-of-care polychemotherapy (SOP) still remains the base for extending the survival of aggressive B-cell lymphoma patients. This review provides a brief overview of the current significance of SOP and new synthetic therapeutic agents for this group of malignancies.