Lecture 32 Flashcards
Diversification of HLA molecules
1) Polymorphism
2) Polygeny
Diversification of TCRs
1) Combinatorial diversity
2) Junctional diversity
3) Pairing (alpha and beta)
Primary diversification of BCR/Igs
1) Combinatorial diversity
2) Junctional diversity
3) Combination of H and L chains
Secondary diversification of BCR/Igs
1) Somatic hypermutation
2) Class switching
Zones of Germinal Center
Dark and Light zone
What is found within the Light zone of Germinal Centers
TFH, FDC (follicular dendritic cells)
Main role of Follicular dendritic cells (FDCs)
Found in germinal center light zone
Retain antigen like SCS macrophages
Lots of receptors for complement protein, not much phagocytosis
Characteristics of B cells first entering germinal center
1) Encountered antigen (signal 1) and have been activated by a T cell at the B-T border (signal 2) and proliferated
2) Can produce IgM/IgD of a baseline affinity (transmembrane)
Class switching in germinal center
Same antigen specificity
IgM/IgD–>IgG, IgA, OR IgE
Light zone is the site of…
Plasma and memory cell differentiation
Dark zone is the site of…
Somatic hypermutation
Function of FDCs in germinal center
Serve as antigen concentration site for future selection and differentiation
Function of TFH in germinal center
Interact with B cells to provide conditions for differentiation and memory cell production
Requirement for B cells to interact with TFH
Linked recognition
B cell must process antigen and present it on MHC II
Plasma Cell outcome after germinal center
1) Stop expressing high levels of BCR
2) Secrete Ig of same specificity as BCR of their progenitor B cell
3) Bind antigen with higher affinity
4) Secreted Ig can be IgG, IgA, or IgE
Memory cell outcome after germinal center
1) Express high levels of BCR
2) BCR has same specificity as progenitor B cell
3) BCR has higher affinity
What is AID
Activation-induced cytidine deaminase
Protein responsible for somatic mutations–>deaminate cytidine residues is ssDNA
Mechanism of AID
Produces point mutations in Ig heavy and light chain V regions
cytidine–>uridine
Some changes are non-productive
Where does somatic hypermutation mainly occur
In CDR loops of V regions
When does class switching occur
After antigen contact (signal 2 for a second time) in germinal center
Signal required to initiate class switch recombination (CSR)
B cells MUST receive costimulatory signals from CD40 to engage in CSR
Cytokine signal received determine which isotype is produced
Where are switch regions located
1) 1 after VDJ region
2) 1 upstream of the constant region to be recombined
Pathway of class switch recombination
B cell + cytokine signal–>transcription upstream of constant region–>DNA is now accessible to AID–>point mutations occur on ssDNA–>nicks are made on both DNA strands (irreversible)–> double stranded DNA breaks upstream of constant region are recombined–>DNA repaired by cutting out intervening DNA–>selected region now adjacent to VDJ region
What is found in the dark zone of the germinal center
Mainly B cells
What handles early reinfection (protective immunity)
Pre-formed antibodies and effector T cells from primary response
What handles late reinfection (immunological memory)
Immune memory B and T cells
What is immunological memory
Ability of immune system to respond more rapidly and more effectively on a second encounter with an antigen
(resistance to re-exposure)
Characteristics of immunological memory
1) Antigen specific
2) Memory responses occur after primary response by lymphocytes generated during late primary response
3) Long-lived
in comparison to primary responses, memory responses have…
1) More antibodies and cells
2) Different antibodies with higher affinity
3) Different lymphocyte features
Where can antibodies be measured
In serum
Which lymphocyte is easier to detect/monitor immunological memory
B cells
Where do Memory T cells reside
In tissue
