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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
B-cell specificity is conferred by the B-cell receptor (BCR) (Figure 2.12), which can be expressed as a membrane-bound receptor or in a soluble form as an antibody (Ab) or immunoglobulin (Ig). The human immune system can produce a highly diverse repertoire of B-cell receptors and antibodies through combinatorial rearrangements of multiple gene segments and somatic mutation. Each antibody clone can bind a specific target epitope, exerting immune functions by blocking or neutralising the target antigen, or flagging it for destruction by other immune cells.
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.
AI and Autoimmunity
Published in Louis J. Catania, AI for Immunology, 2021
For the first time, scientists at the Human Vaccines Project are combining systems biology with artificial intelligence to understand one of the most significant remaining frontiers of human health, the human immune system.45 Perhaps the most exciting application of AI in immunology is found in the Human Vaccines Project. Researchers are comprehensively sequencing the human immune system, a system billions of times larger than the human genome. The goal is to encode the genes responsible for circulating B-cell receptors. This can provide potential new antibody targets for vaccines and therapeutics that work across populations. The Project seeks to define the genetic underpinnings of people’s ability to respond and adapt to an immense range of diseases.46 The SARS-CoV-2 COVID-19 pandemic will certainly expedite further progress on this critical area of clinical research. The study specifically looked at one part of the adaptive immune system, the circulating B-cell receptors that are responsible for the production of antibodies, considered the primary determinant of immunity in people. The receptors form unique sequences of nucleotides known as receptor “clonotypes.” This creates a small number of genes that can lead to an incredible diversity of receptors, allowing the immune system to recognize almost any new pathogen.
Nanomaterials in tuberculosis DNA vaccine delivery: historical perspective and current landscape
Published in Drug Delivery, 2022
Xing Luo, Xiaoqiang Zeng, Li Gong, Yan Ye, Cun Sun, Ting Chen, Zelong Zhang, Yikun Tao, Hao Zeng, Quanming Zou, Yun Yang, Jieping Li, Hongwu Sun
The delivery of protein expressed as an adjuvant molecule with plasmid DNA causes enhanced protective efficacy against a challenge infection with M. tuberculosis H37Rv, emphasizing the significant role of CD4+ helper T cells (Th1-type) in protection (Tanghe et al., 2001, Yang et al., 2011). Figure 7 shows self-assembled protein nanoparticles in vaccine design. B- and T-cell stimulation and activation, and the subsequent secretion of antigen-specific antibodies by plasma cells depend on the effective cross-linking between B-cell surface immunoglobulins (B-cell receptors, BCRs) and recognition patterns presented by the pathogen. The high-density and structurally ordered antigenic array presented by nanoparticle vaccines facilitate multiple binding events to occur simultaneously between the self-assembling protein nanoparticles and host-cell BCRs (Lopez-Sagaseta et al., 2016). Several paradigms have been reported for the design of TB DNA-vaccine delivery vectors using protein-backbone engineering. The synthetic antimicrobial peptide KLKL5KLK exhibits effective immunostimulant properties that enhance and prolong immune responses against M. tuberculosis in combination with DNA vaccines (Li et al., 2008). Therefore, these self-assembled peptide and protein nanomaterials represent novel TB DNA-vaccine delivery systems with immense application prospects.
Paediatric-type follicular lymphoma arising in conjunction with pregnancy
Published in Acta Oncologica, 2021
Stefano Fratoni, Pasquale Niscola
The case of PTNFL was observed by us in a young female. This particularly rare lymphoma typically presents with isolated lymphadenopathy in the head and neck. Despite the ‘blastoid’ features on histological examination, PTNFL has an extremely indolent clinical behaviour, being surgical excision alone virtually curative [5–6]. Nonetheless, exceptional cases of transformation in high-grade B-cell lymphoma may occur [7]. The differential diagnosis of PTNFL may be quite troublesome. The recognition of this particularly rare lymphoma is important for hematopathologist, given that overlap with florid reactive follicular hyperplasia (RFH) may be a practical problem. Reliable criteria for its diagnosis have been previously illustrated [8]. In this setting the immunohistochemical expression of forehead box protein P1 FOXP-1 may be a useful tool to distinguish PTNFL from RFH [9]. Nonetheless, establish clonality by B-cell receptor studies is mandatory in the diagnostic work up. On the other hand, purely follicular large B-cell lymphoma with IRF4 rearrangement may mimic PTNFL. The strong nuclear expression of IRF4/MUM1 along with rearrangement of IRF4 with an IGH locus, usually allows the distinction between the two [10].
Nanovesicles released by OKT3 hybridoma express fully active antibodies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Mariantonia Logozzi, Rossella Di Raimo, Francesca Properzi, Stefano Barca, Daniela F. Angelini, Davide Mizzoni, Mario Falchi, Luca Battistini, Stefano Fais
An important feature of antibodies is that they are present in two forms, each with different features: (i) soluble secreted immunoglobulins, which contribute to the body’s immune surveillance; (ii) membrane-bound immunoglobulins which form B-cell Receptors and are responsible for maturation, activation, and differentiation of B cells. These latter forms, expressed in membranes, could be more functional. For example, other transmembrane type II receptors such as Fas ligand, may exert different functions when expressed on either a membrane or in its soluble form18–20. It is conceivable that also antibodies may be more active when expressed on a plasmamembrane. In fact, it has been shown as some monoclonal antibodies are more active in triggering cellular functions (e.g. activation, proliferation and cytokine release) when immobilised on a surface21–23.