Adaptive immunity 2

Question 1

what is isotope switching mediated by?

when does it occur?

what is it regulated by?

Answer 1

switch sequences on the 5’ side of each C-gene

during an active immune response
-> T cells proliferate

cytokines secreted by antigen activated T-cells

Question 2

what is the purpose of isotope switching?

what is unaffected?

Answer 2

provides antibodies with different effector functions

doesn’t contribute to diversity of antigen binding
- still have the same antigen specificity

Question 3

what happens once a cell has switched?

Answer 3

it cannot switch back to original as DNA is lost from genome

Question 4

what are the 6 phases of B cell development?

Answer 4

1. repertoire assembly
2. negative selection
3. positive selection
4. searching for infection
5. finding infection
6. attacking infection

Question 5

describe repertoire assembly

Answer 5

generation of diverse + clonal expressed B cell receptors in the bone marrow

Question 6

describe negative and positive selection

Answer 6

alteration, elimination or inactivation of B cell receptors that bind to components of the human body

promotion of fraction of naive B cells to become mature B cells in secondary lymphoid tissues

Question 7

describe searching for infection

Answer 7

recirculation of mature B cells between lymph, blood and secondary lymphoid tissues

Question 8

describe finding infection

Answer 8

activation + clonal expansion of B cells by pathogen-derived antigens in secondary lymphoid tissues

Question 9

describe attacking infection

Answer 9

differentiation into antibody-secreting plasma cells + memory B cells in secondary lymphoid tissues

Question 10

what are the stages of B cell development marked by?

Answer 10

steps in rearrangement + expression of Ig genes

Question 11

what happens in the large pre-B-cell stage?

Answer 11

proliferate

all produce same heavy chain

-> produces populations of cells that rearrange light chains independently of each other

Question 12

describe a pre-B-cell receptor

Answer 12

pre-B has a surrogate light chain made up of 2 polypeptides
= VpreB + lambda 5

no variability in these polypeptides

associates with accessory proteins at cel surface
-> activates intracellular signalling to proliferate

Question 13

what is B-cell development dependent on?

what happens as stem cells mature into B cells?

Answer 13

non-lymphoid stromal cells
-> make contact with B-cells via adhesion molecules
+ secrete factors that influence development

start to produce different receptors
move towards bone marrow cavity

Question 14

give an example of a protein-protein interaction that drives B cell development

Answer 14

IL-7 receptor on cell binds to IL-7

Question 15

what are unproductive rearrangements?

what are productive rearrangements?

why are these important?

Answer 15

gene rearrangements that cannot be translated into protein
e.g. due to frame shift or stop codon

rearrangements that give rise to a functionalists immunoglobulin chain

only B-cells that produce functional immunoglobulin survive
- otherwise apoptosis

Question 16

how many chances do B cells have to produce functional chains?

what antibodies do the different light chain rearrangements produce?

Answer 16

2 chances to produce a functional heavy chain

4 chances to produce a functional light chain

kappa chain IgM
lambda chain IgM

Question 17

What is TdT?

What is its function?

When is it highly expressed?

Answer 17

Terminal deoxynucleotidyl transferase

N-nucleotide addition

only when heavy chain is been rearranged
- adds non-template nucleotides

Question 18

what do tolerance mechanisms involve?

why must this occur?

Answer 18

the removal/inactivation of self-reactive B cells
- i.e. those with Igs that bind to normal constituents of the body

to prevent autoimmune diseases

Question 19

what are the 2 types of tolerance and what’s the difference?

Answer 19

central tolerance
= in the bone marrow

peripheral B-cell tolerance
= continual low level antigen exposure could lead to anergy (non-responsiveness)

Question 20

what happens if there is a self-reactive B cell in bone marrow?

Answer 20

cell may undergo receptor editing:
continues to rearrange the light chain
-> makes new IgM with different specificity

if new receptor is self-reactive

• > continues rearranging light chain
• > if no further rearrangements possible = clonal deletion + apoptosis

if new IgM is not self-reactive
= B cell leaves bone marrow

Question 21

what do naive B cells compete for once they are circulating in the blood?

why?

Answer 21

access to primary lymphoid follicles

to receive survival signals from follicular dendritic cells
-> naive immature B cells become naive mature B cells (half life ~100days)

if immature B cells don’t receive signals
= half life ~ 3-5 days

Question 22

where do mature B cells encounter a specific antigen?

what then happens?

Answer 22

secondary lymphoid tissue

become activated by CD4 helper T cells
-> provide signals that activate B cells to proliferate + differentiate further

Question 23

what do B cells differentiate into once activated?

Answer 23

plasma cells

OR could migrate to primary follicle,

• > change morphology
• > become a secondary lymphoid follicle containing a germinal centre

Question 24

what happens to those B cells in the secondary lymphoid follicle?

Answer 24

become proliferating centroblasts

-> mature into isotope switched somatically hyper mutated non-dividing centrocytes

Question 25

how are B-cells with the highest affinity for an antigen selected?

what happens to cells that survive this state?

Answer 25

by affinity maturation

proliferate and differentiate into plasma cells + memory B cells (long-lived)
- express high affinity IgG, IgA or IgE

Question 26

how do antigens get to the lymph node?

Answer 26

via the afferent lymphatic vessel