B Cells 6 Flashcards
what are the 3 main sources of diversity in adaptive immunity?
- HLA molecules
- TCRs
- BCRs/Ig
what are the 2 types of diversity in HLA molecules?
- polymorphism
- polygeny
what are the 3 types of diversity in TCRs?
- combinatorial diversity
- junctional diversity
- pairing (alpha + beta)
what are the 2 types of diversity in BCR/Ig?
- Primary diversification
- secondary diversification
what are the 3 types of primary diversification?
- combinatorial diversity
- junctional diversity
- combo of H and L chains
what are the 2 types of secondary diversification?
- somatic hypermutation
- class switching
what are the 2 zones of the germinal center?
- dark zone
- light zone
where are T_FH found in the germinal center? how do they get there?
T_FH found in the light zone –> migrate from T cell zone to germinal center
where are follicular DCs located?
what is their role?
what other type of cell are they similar to?
FDCs located in light zone
they retain Ag like SCS macrophages
what are the 2 properties of B cells that enter the germinal center?
- already undergone signal 1, 2, and proliferation
- can produce transmembrane IgM/IgD with baseline affinity
what happens to B cells in the germinal center?
they undergo somatic hypermutation or class switching
how does B cell specificity change with somatic hypermutation? with class switching?
Ag specificity always the same!!
what must happen before secondary diversification?
in the germinal center, B cell must receive signal 1 and 2 AGAIN
what occurs in the light zone of the germinal center?
primary site of plasma and memory cell differentiation
what occurs in the dark zone of the germinal center?
somatic hypermutation
what is the role of FDCs?
Ag concentration site for future selection and differentiation
what is the role of T_FH
T_FH provides conditions for differentiation and memory cell production
what happens to B cells in the dark zone?
undergo somatic hypermutation via point mutation in V region –> cells have higher affinity (same specificity)
what happens to B cells after they undergo somatic hypermutation?
they migrate to the light zone and compete to bind antigen on FDC
describe what happens to high and low affinity B cells when they compete for antigen on FDC
where does their affinity come from? what is the process called?
HIGH AFFINITY B CELLS –> bind Ag –> signal 1 (again)
LOW AFFINITY B CELLS –> don’t bind Ag –> die by apoptosis
affinity is due to somatic hypermutation, then the process of selecting HIGH AFFINITY B cells via binding to FDC is affinity maturation
what happens to the antigen when high affinity B cells bind it during affinity maturation?
Ag:BCR internalized then presented on MHC II
What happens when B cell presents Ag on MHC II?
interacts with T_FH via TCR and CD40 for linked recognition –> signal 2 (again)
what happens after B cells undergo a second signal 2?
B cells enter dark zone and undergo additional somatic hypermutation, as well, will receive cytokines from T_FH for class switching
what happens to plasma cells after they receive signal 1 and 2 a second time? (4)
- stop expressing high levels of BCR
- secrete Ig of same specificity but diff subtype as BCR of progenitor
- secreted Ig can be IgG, IgA, IgE
- should bind Ag with higher affinity
what happens to memory B cells after somatic hypermutation? (3)
- express high levels of BCR
- BCR has same specificity as progenitor B cell
- BCR should have higher affinity
what protein is responsible for somatic hypermutation?
AID –> activation-induced cytidine deaminase
what does AID do?
converts cytidine to uridine (i.e. deaminates it) and removes it
what happens after AID acts on cytidine?
mismatch repair pathway and error-prone polymerase activity produces individual, random point mutations in Ig heavy and light chain variable regions
are all point mutations helpful?
no, some will be a stop codon, cause improper folding, etc and will be degraded
where does somatic hypermutation mainly occur on the Ig?
in CDR loops of V regions
what is affinity maturation?
select B cells that can bind, process, and present more Ag to T cells for cytokine assistance
why does somatic hypermutation occur multiple times?
to increase the Ab affinity with increased exposure
where and when does class switching recombination occur?
occurs within the germinal center after SIGNAL 2 (#2)
what are the 2 signals required for class switching recombination?
- costimulatory signals from CD40
- cytokine signal from T_FH that determines the Ig isotype that will be produced
what changes during class switching?
constant region
where does class switching recombination occur on the mRNA? how does it work?
between switch regions, one after the VDJ region and one before/upstream of the constant region to be used
then cuts out every constant region in the middle, allowing a constant region further down the line (next to the switch region) to be recombined
describe the process of class switch recombination (6 steps)
- B cell receives cytokine signal –> transcription is activated in SWITCH regions
- TFs bind and allow the single strand DNA to be accessible to AID
- nicks made on DNA
- DS break repair machinery repairs the break by forming a loop and cutting out the DNA
- now, the selected constant region is adjacent to VDJ
what is protective immunity?
early reinfection is handled by pre-formed Abs/effector T cells that are primary (aka LEFT OVER) from the first response
what is the hallmark of adaptive immunity?
MEMORY!
what is left behind after the antigen is cleared from the primary response?
memory lymphocytes
what happens upon second exposure?
memory lymphocytes are re-stimulated
how does the secondary response compare to the primary response?
faster, more significant, and better response
does the memory or primary response last longer?
memory!
what are 2 ways you develop memory/resistance?
- having the exposure
- vaccinated
why is the memory response better?
- more Abs, more cells
- diff Abs w higher affinity, diff lymphocyte features
is it easier to detect/monitor for B or T cells? why?
B cells! bc Ab can be measured in serum, memory T cells are in tissue
what cytokines induce IgE?
TH2 cytokines (IL-4,5,13)
