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Introduction to the immune system
MHC class I and MHC class II molecules
B-cell activation and differentiation
Cell-mediated immunity of CD4 cells
Cell-mediated immunity of natural killer and CD8 cells
Somatic hypermutation and affinity maturation
Contracting the immune response and peripheral tolerance
B- and T-cell memory
Anergy, exhaustion, and clonal deletion
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The adaptive immune response is highly specific for each invader, and that’s because the cells of the adaptive immune response have receptors that differentiate friendly bacteria and potentially deadly pathogens from their unique parts - called antigens.
And the antigen receptors for T cells and B cells have a lot of things in common, one of which is that they share the same mechanism - called VDJ rearrangement - to generate a massively diverse set of receptors.
VDJ stands for variability, diversity, and joining, respectively, and VDJ rearrangement has 4 key characteristics that help ensure that each antigen receptor is unique.
First, each individual inherits multiple V, D, and J gene segments; second, the V, D, and J gene segments randomly recombine - meaning that any V can pair with any D and any J; third, there’s recombinational inaccuracy - meaning that this process is purposefully error prone - which leads to additional variation; and fourth, there’s random reassortment of two chains - meaning that this process involves two different chains that come together to make the receptor.
First, let’s look at our antigen receptors. The B cell receptor, or BCR, is essentially an antibody, except that it has a transmembrane part that goes through the membrane and attaches the receptor to the surface of a B cell.
Just like antibodies, the B cell receptor has a heavy chain and a light chain.
There are two Fab regions on every B cell receptor.
Then there’s the constant region or fragment called the fragment - constant or Fc region, which is the part that determines what class of B cell receptor it will be - for example, IgM or IgD, and whether or not it will remain a membrane bound B cell receptor or if it will get secreted as a free floating antibody.
VDJ rearrangement is a process by which the genes responsible for encoding the variable region of the B-cell receptor and T-cell receptor are rearranged to create a diverse repertoire of receptors capable of recognizing a wide variety of antigens.
During VDJ rearrangement, DNA segments called V (variable), D (diversity), and J (joining) are rearranged to form the coding sequence for the receptor variable region. The process is mediated by recombination-activating genes (RAG1 and RAG2) and involves the introduction of double-strand breaks at specific recombination signal sequences (RSS) flanking the V, D, and J segments, followed by joining of the broken ends.
The resulting receptor variable region diversity is crucial for adaptive immunity, allowing the immune system to recognize and respond to a wide range of potential pathogens. However, errors in VDJ rearrangement can lead to autoimmune disease, immunodeficiency, or cancer.
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