Lecture 32

Question 1

Diversification of HLA molecules

Answer 1

1) Polymorphism
2) Polygeny

Question 2

Diversification of TCRs

Answer 2

1) Combinatorial diversity
2) Junctional diversity
3) Pairing (alpha and beta)

Question 3

Primary diversification of BCR/Igs

Answer 3

1) Combinatorial diversity
2) Junctional diversity
3) Combination of H and L chains

Question 4

Secondary diversification of BCR/Igs

Answer 4

1) Somatic hypermutation
2) Class switching

Question 5

Zones of Germinal Center

Answer 5

Dark and Light zone

Question 6

What is found within the Light zone of Germinal Centers

Answer 6

TFH, FDC (follicular dendritic cells)

Question 7

Main role of Follicular dendritic cells (FDCs)

Answer 7

Found in germinal center light zone
Retain antigen like SCS macrophages
Lots of receptors for complement protein, not much phagocytosis

Question 8

Characteristics of B cells first entering germinal center

Answer 8

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)

Question 9

Class switching in germinal center

Answer 9

Same antigen specificity
IgM/IgD–>IgG, IgA, OR IgE

Question 10

Light zone is the site of…

Answer 10

Plasma and memory cell differentiation

Question 11

Dark zone is the site of…

Answer 11

Somatic hypermutation

Question 12

Function of FDCs in germinal center

Answer 12

Serve as antigen concentration site for future selection and differentiation

Question 13

Function of TFH in germinal center

Answer 13

Interact with B cells to provide conditions for differentiation and memory cell production

Question 14

Requirement for B cells to interact with TFH

Answer 14

Linked recognition
B cell must process antigen and present it on MHC II

Question 15

Plasma Cell outcome after germinal center

Answer 15

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

Question 16

Memory cell outcome after germinal center

Answer 16

1) Express high levels of BCR
2) BCR has same specificity as progenitor B cell
3) BCR has higher affinity

Question 17

What is AID

Answer 17

Activation-induced cytidine deaminase
Protein responsible for somatic mutations–>deaminate cytidine residues is ssDNA

Question 18

Mechanism of AID

Answer 18

Produces point mutations in Ig heavy and light chain V regions
cytidine–>uridine
Some changes are non-productive

Question 19

Where does somatic hypermutation mainly occur

Answer 19

In CDR loops of V regions

Question 20

When does class switching occur

Answer 20

After antigen contact (signal 2 for a second time) in germinal center

Question 21

Signal required to initiate class switch recombination (CSR)

Answer 21

B cells MUST receive costimulatory signals from CD40 to engage in CSR
Cytokine signal received determine which isotype is produced

Question 22

Where are switch regions located

Answer 22

1) 1 after VDJ region
2) 1 upstream of the constant region to be recombined

Question 23

Pathway of class switch recombination

Answer 23

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

Question 24

What is found in the dark zone of the germinal center

Answer 24

Mainly B cells

Question 25

What handles early reinfection (protective immunity)

Answer 25

Pre-formed antibodies and effector T cells from primary response

Question 26

What handles late reinfection (immunological memory)

Answer 26

Immune memory B and T cells

Question 27

What is immunological memory

Answer 27

Ability of immune system to respond more rapidly and more effectively on a second encounter with an antigen
(resistance to re-exposure)

Question 28

Characteristics of immunological memory

Answer 28

1) Antigen specific
2) Memory responses occur after primary response by lymphocytes generated during late primary response
3) Long-lived

Question 29

in comparison to primary responses, memory responses have…

Answer 29

1) More antibodies and cells
2) Different antibodies with higher affinity
3) Different lymphocyte features

Question 30

Where can antibodies be measured

Answer 30

In serum

Question 31

Which lymphocyte is easier to detect/monitor immunological memory

Answer 31

B cells

Question 32

Where do Memory T cells reside

Answer 32

In tissue