B cell immunity Flashcards
What are the two types of B cell activation?
T-dependent and T-independent responses
What is a T-dependent B cell response?
A response where B cells require help from T helper cells CD4+ for antibody production
What is a T-independent B cell response?
A response where B cells are activated directly by antigens without T cell help producing mainly IgM - this is faster than a T-dependant response which can be useful for microbial antigens
Where does B cell activation occur?
In secondary lymphoid tissues like lymph nodes and spleen
What is the role of B cell receptors BCRs?
They bind antigens and initiate B cell activation
What happens when a B cell binds an antigen (in terms of T cells)?
The antigen is internalized degraded to short polypeptides and bind to an MHC class II molecule, which presents the antigen fragments to T helper cells
What is linked recognition?
A process where B cells and T cells recognise different epitopes of the same antigenic complex and interact - they must have both come into contact with the same antigen for this to occur
How do T helper cells activate B cells?
By the binding of CD40 ligand to the CD40 on the B cell and by production of cytokines that stimulate B cell proliferation antibody production somatic hypermutation and class switching
What is somatic hypermutation?
A process where point mutations occur in the antibody genes, where the mutations that occur in the variable region of the antibody increase antibody affinity.
What is affinity maturation?
The selection of B cells producing high-affinity antibodies during somatic hypermutation in germinal centers
What enzyme is required for somatic hypermutation?
Activation-Induced Cytidine Deaminase AID
What is class switch recombination?
A process that changes the antibody class produced for example from IgM to IgG IgA or IgE while retaining antigen specificity
How does class switching occur?
Through recombination of the heavy chain constant region guided by switch regions and regulated by T cell cytokines
What are switch regions in class switching?
GC-rich DNA regions that are about 2-10 kb long, near constant region genes that enable recombination during class switching
What is the role of cytokines in class switching?
Cytokines produced by T cells regulate which antibody class is produced for example IL4 promotes IgE, Transforming Growth Factor Beta and IL5 promotes IgA1, Inteferon Gamma produces IgG3
What is the primary antibody response?
The initial response to an antigen characterized by IgM production with lower affinity
What is the secondary antibody response?
A faster stronger response with higher antibody affinity and different classes mainly IgG
What are germinal centers?
Structures in lymphoid tissues where B cells undergo somatic hypermutation affinity maturation and class switching
What are plasma B cells?
B cells that are specialized for antibody production often migrating to the bone marrow or inflamed tissues
What is the importance of immunological memory?
It allows for a faster and more effective secondary response to previously encountered antigens
What are the two types of T-independent antigens?
TI1 bacterial LPS activating through TLR4 and TI2 repeated antigen structures causing BCR cross-linking
What is the basis of conjugate vaccines?
Attaching polysaccharides to protein carriers to promote T-dependent B cell responses
What is the role of AID in class switching?
It introduces mutations in switch regions to facilitate recombination/loop out parts of the DNA resulting in antibody class change
What happens in the dark zone of germinal centers?
B cells undergo somatic hypermutation leading to affinity maturation (an increase in the affinity of the antibody molecule for antigen)
What is the role of MHC class II in B cell activation?
It presents processed antigens to T helper cells facilitating their interaction and activation
What type of antibody is primarily produced in T-independent responses?
IgM which has lower affinity compared to T-dependent responses
What is a naïve B-cell?
B-cells that have matured but not encountered the antigen yet are considered naïve B-cells.
What are the two phases of the Primary B cell response?
Phase 1: B cells that encounter antigen and activated by T cells form a primary focus
Leads to production of plasma cells and prompt secretion of IgM
Phase 2: Some activated B cells form germinal centres, - which are areas of proliferating B-cells and a small number of T-cells; This results in B-cell modifications such as somatic hypermutation and class switching to produce a more effective immune response
Why do plasma cells have large amounts of endoplasmic reticulum?
Endoplasmic reticulum is key to production of proteins which is what makes up antibodies.
What is the proportion of B to T cells in the Germinal centres?
90% proliferating B cells, 10% T cells
What causes swollen lymph nodes/tonsils?
Germinal centres are dynamic and can grow when there is an infection.
What occurs in the light zone of the Germinal Centres?
Class-switching.
How is the affinity of an antibody increased for an antigen?
Hypermutation of the Variable regions of the antibody via single nucleotide/amino acid changes via AID
What is the role of AID in Somatic Hypermutation?
AID changes the cytosine in DNA to uracil by deamination, which triggers base pair mismatch and repair.
What does Somatic Hypermutation require for testing?
Requires antigen which is delivered to the germinal centre, B-cell antibodies are tested against antigen and the B-cell that produces the highest affinity antibody is selected.
What is looping out?
The DNA for different antibody classes is all on one gene, looping out is the removal of the beginning genes to reach the gene that produces the desired class.
