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Related Concept Videos

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
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B Cell Activation and Differentiation01:24

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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The Two-State Receptor Model01:29

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The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
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T Cell Activation and Clonal Selection01:22

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Cells of the Adaptive Immune Response01:23

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy
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Spatial Stochastic Model of the Pre-B Cell Receptor.

Romica Kerketta, M Frank Erasmus, Bridget S Wilson

    IEEE/ACM Transactions on Computational Biology and Bioinformatics
    |April 28, 2022
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    Summary
    This summary is machine-generated.

    Immature B lymphocyte survival depends on pre-B cell receptor (pre-BCR) tonic signaling. Differences in receptor dynamics between B-ALL cell lines impact pre-BCR aggregation and downstream signaling.

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    Visualizing Surface T-Cell Receptor Dynamics Four-Dimensionally Using Lattice Light-Sheet Microscopy
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    Area of Science:

    • Immunology
    • Cell Biology
    • Computational Biology

    Background:

    • Immature B lymphocyte survival and proliferation rely on tonic signaling from the pre-B cell receptor (pre-BCR).
    • Ligand-independent tonic signaling is crucial for B cell development and implicated in precursor B acute lymphoblastic leukemia (B-ALL).
    • Understanding sustained signaling from transient receptor events and membrane landscape effects is critical.

    Purpose of the Study:

    • To investigate how repeated, transient pre-BCR interactions lead to sustained signaling.
    • To assess the impact of receptor accumulation and membrane dynamics on pre-BCR signaling.
    • To model spatial stochastic events of pre-BCR aggregation and downstream signaling.

    Main Methods:

    • Developed a spatial stochastic, rule- and agent-based model for pre-BCR signaling.
    • Incorporated novel parameters from single particle tracking of pre-BCR on B-ALL cell lines (697 and Nalm6).
    • Analyzed receptor dimer dissociation rates and diffusion coefficients using live cell tracking.

    Main Results:

    • Identified characteristic differences in pre-BCR dimer dissociation rates and diffusion coefficients between 697 and Nalm6 B-ALL cell lines.
    • Observed that Nalm6 cells exhibit lower off-rates and diffusion coefficients for pre-BCR compared to 697 cells.
    • Demonstrated that these dynamic differences lead to increased formation of higher-order pre-BCR oligomers and higher downstream phosphorylation levels in Nalm6 cells.

    Conclusions:

    • Receptor dynamics, specifically off-rate and diffusion, significantly influence pre-BCR aggregation and signal initiation.
    • The membrane landscape and receptor mobility play a key role in modulating tonic pre-BCR signaling.
    • These findings provide insights into B-ALL pathogenesis and potential therapeutic targets.