B-lymphocytes Flashcards
What is the difference between the types of epitopes recognised by B cells and T cells?
T cells = sequences (linear epitope)
B cells = structure (tertiary)
What are the types of adaptive immune response?
Humoral : B cells- antibodies
Cell-mediated: T cells-cytokines, killing
Describe the structure of the B cell receptor and how it transmits signals into the cell.
The BCR is a membrane-anchored antibody It is associated with two transmembrane domains that are di-sulphite linked heterodimers called Ig-alpha and Ig-beta which have cytoplasmic tails that are long enough to transmit a signal to the inside of the cell Antigen binding to the BCR causes a conformational change, which drives signalling via the Ig-alpha Ig-beta heterodimer
What is the process by which B cells and T cells generate the variety in their receptors/antibodies?
Immunoglobulin Gene Rearrangement
How are each BCR receptor chain encoded?
By separate multi gene families on different chromosomes.
During B cell maturation these segments are rearranged and brought together.
Describe the generation of variation in the light chain.
There are 70 variable unit- 40 in kappa and 30 in lambda
- The B cell begins with germline DNA (immature B cell) -As B cell develop, they get rid of most of the variable unit and leave a few Variable and Joining regions ((this is random)
- This means that there is a large number of different combinations of segments forming a large number of different antigen specificities.
How does further variation arise?
Different splicing patterns give rise to more variation
What enzyme is involved in the removal of unused segments of DNA, which gene codes for this and what disease is caused by deficiency of this gene/enzyme?
- the unused DNA is looped out and removed
- V(D)J recombinase- enables DNA recombination.
- Rag genes code for this : deficiency leads to SCID
Describe the generation of variation in the heavy chain.
- start off with germline DNA
- the different regions shuffle and rearrange via recombination
- a few V,D and J regions are passed down
- the constant region determines the type (class) of antibody
- AlSO get variation in splicing
What determines the class of the immunoglobulin?
The constant region of the heavy chain
In what order does the gene rearrangement take place?
The heavy chain undergoes VDJ rearrangement before the light chain
What three things can happen to B cells once they’ve recognised their antigens?
- Affinity Maturation: antibody response improves
- Memory cell: becomes stored for later exposure to the same infection
- Plasma cell: B cells which physically make the antibody
What is the general rule about B cell and T cell activation?
Naive antigen-specific lymphocytes cannot be activated by antigen alone. It needs co-stimulation to be activated – antigen alone is not enough.
What accessory signal do B cells need?
- Directly from microbial constituents
- T helper cell
What are the two pathways by which B cell production is achieved?
Thymus dependent and Thymus independent
Describe the T independent pathway and which immunoglobin class can do this
ONLY IgM
This is associated with long polysaccharides with a repeating subunit
The repeating unit can bind to several BCRs and drive cross-linking
Secondary signal is required.There will also be PAMPs such as LPS that provide co-stimulation ( accessory signal)
Describe the T dependent pathway.
All Ig classes
Antigen has to be taken up by Dendritic cells and B cells at the same time
B cells process and present the antigen on MHC Class II
Dendritic cells also present the SAME antigen on MHC Class II to a T helper cell which recognises it through TCR.
The T helper cell becomes activated and undergoes clonal selection .The T helper cell then moves to the lymph nodes, and binds with the B cell which has the same class MHC class II,and activates it. This provides the second signal.
certain molecules on the T cell activates the B cell which then becomes a plasma cell.
What happens after T helper cells bind to the antigen?
- T helper cells secrete lymphokines after recognition of the antigenic/self complex on the surface of the B cell.
- B cell enters the cell cycle and develops into a clone of cells with identical BCRs.
Describe the process of immunoglobulin class switching.
T helper cells (once bound to the B cell) can release various cytokines – depending on the cytokine released, the immunoglobulin class can be switched. Variable region stays the same and you switch out different exons to give you a different constant region.
What drives the improvement of the immune response between primary and secondary exposures?
Somatic Hypermutation and Affinity Maturation ( the antibodies you produce the second time are better than the ones you generate on first exposure)
Describe the process of somatic hypermutation.
Point mutations are induced in the VDJ regions by (Activation-induced deaminase – AID) which cause slight conformational changes in the antigen-binding site. If the change is beneficial and improves the binding between antibody and antigen then it survives Otherwise the B cells are killed by apoptosis.
