Adaptive immunity 2 Flashcards
(26 cards)
what is isotope switching mediated by?
when does it occur?
what is it regulated by?
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
what is the purpose of isotope switching?
what is unaffected?
provides antibodies with different effector functions
doesn’t contribute to diversity of antigen binding
- still have the same antigen specificity
what happens once a cell has switched?
it cannot switch back to original as DNA is lost from genome
what are the 6 phases of B cell development?
- repertoire assembly
- negative selection
- positive selection
- searching for infection
- finding infection
- attacking infection
describe repertoire assembly
generation of diverse + clonal expressed B cell receptors in the bone marrow
describe negative and positive selection
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
describe searching for infection
recirculation of mature B cells between lymph, blood and secondary lymphoid tissues
describe finding infection
activation + clonal expansion of B cells by pathogen-derived antigens in secondary lymphoid tissues
describe attacking infection
differentiation into antibody-secreting plasma cells + memory B cells in secondary lymphoid tissues
what are the stages of B cell development marked by?
steps in rearrangement + expression of Ig genes
what happens in the large pre-B-cell stage?
proliferate
all produce same heavy chain
-> produces populations of cells that rearrange light chains independently of each other
describe a pre-B-cell receptor
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
what is B-cell development dependent on?
what happens as stem cells mature into B cells?
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
give an example of a protein-protein interaction that drives B cell development
IL-7 receptor on cell binds to IL-7
what are unproductive rearrangements?
what are productive rearrangements?
why are these important?
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
how many chances do B cells have to produce functional chains?
what antibodies do the different light chain rearrangements produce?
2 chances to produce a functional heavy chain
4 chances to produce a functional light chain
kappa chain IgM
lambda chain IgM
What is TdT?
What is its function?
When is it highly expressed?
Terminal deoxynucleotidyl transferase
N-nucleotide addition
only when heavy chain is been rearranged
- adds non-template nucleotides
what do tolerance mechanisms involve?
why must this occur?
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
what are the 2 types of tolerance and what’s the difference?
central tolerance
= in the bone marrow
peripheral B-cell tolerance
= continual low level antigen exposure could lead to anergy (non-responsiveness)
what happens if there is a self-reactive B cell in bone marrow?
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
what do naive B cells compete for once they are circulating in the blood?
why?
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
where do mature B cells encounter a specific antigen?
what then happens?
secondary lymphoid tissue
become activated by CD4 helper T cells
-> provide signals that activate B cells to proliferate + differentiate further
what do B cells differentiate into once activated?
plasma cells
OR could migrate to primary follicle,
- > change morphology
- > become a secondary lymphoid follicle containing a germinal centre
what happens to those B cells in the secondary lymphoid follicle?
become proliferating centroblasts
-> mature into isotope switched somatically hyper mutated non-dividing centrocytes
