B-lymphocytes

Question 1

What is the difference between the types of epitopes recognised by B cells and T cells?

Answer 1

T cells = sequences (linear epitope)

B cells = structure (tertiary)

Question 2

What are the types of adaptive immune response?

Answer 2

Humoral : B cells- antibodies

Cell-mediated: T cells-cytokines, killing

Question 3

Describe the structure of the B cell receptor and how it transmits signals into the cell.

Answer 3

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

Question 4

What is the process by which B cells and T cells generate the variety in their receptors/antibodies?

Answer 4

Immunoglobulin Gene Rearrangement

Question 5

How are each BCR receptor chain encoded?

Answer 5

By separate multi gene families on different chromosomes.

During B cell maturation these segments are rearranged and brought together.

Question 6

Describe the generation of variation in the light chain.

Answer 6

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.

Question 7

How does further variation arise?

Answer 7

Different splicing patterns give rise to more variation

Question 8

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?

Answer 8

• the unused DNA is looped out and removed
• V(D)J recombinase- enables DNA recombination.
• Rag genes code for this : deficiency leads to SCID

Question 9

Describe the generation of variation in the heavy chain.

Answer 9

• 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

Question 10

What determines the class of the immunoglobulin?

Answer 10

The constant region of the heavy chain

Question 11

In what order does the gene rearrangement take place?

Answer 11

The heavy chain undergoes VDJ rearrangement before the light chain

Question 12

What three things can happen to B cells once they’ve recognised their antigens?

Answer 12

• 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

Question 13

What is the general rule about B cell and T cell activation?

Answer 13

Naive antigen-specific lymphocytes cannot be activated by antigen alone. It needs co-stimulation to be activated – antigen alone is not enough.

Question 14

What accessory signal do B cells need?

Answer 14

• Directly from microbial constituents

- T helper cell

Question 15

What are the two pathways by which B cell production is achieved?

Answer 15

Thymus dependent and Thymus independent

Question 16

Describe the T independent pathway and which immunoglobin class can do this

Answer 16

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)

Question 17

Describe the T dependent pathway.

Answer 17

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.

Question 18

What happens after T helper cells bind to the antigen?

Answer 18

• 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.

Question 19

Describe the process of immunoglobulin class switching.

Answer 19

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.

Question 20

What drives the improvement of the immune response between primary and secondary exposures?

Answer 20

Somatic Hypermutation and Affinity Maturation ( the antibodies you produce the second time are better than the ones you generate on first exposure)

Question 21

Describe the process of somatic hypermutation.

Answer 21

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.