Antibody Mediated Humoral Immunity - Bowden (Completed)

Question 1

What are the co-receptors of a B cell? 6

Answer 1

CD19

CD81

CR2 (CD21)

Question 2

What are the two major subsets of B cells? 6

Answer 2

Follicular B cells

Marginal B cells

Question 3

What is a marginal B cell? 6

Answer 3

Resides in the spleen

Identifies blood-borne polysaccharide Ags

Question 4

What is a follicular B cell? 6

Answer 4

Recirculating B cells

Make up the majority of B cells

Question 5

What happens each time a naive B cell enters a lymph node? 7

Answer 5

They receive a survival signal (FDC), if they don’t receive this signal they degenerate

Question 6

What is the first B cell signal? 9

Answer 6

Ag binding to membrane-bound Igs

must occur with 2 or more BCRs to conduct the signal

Question 7

How B cell intracellular signaling differ from T cell intracellular signaling? 9

Answer 7

The ONLY difference is the initial Src kinase that interacts with Igα and Igβ

Lyn
Fyn
Blk

Question 8

Besides cross-linking with two membrane Ig’s how else can the first B cell signal be generated? 10

Answer 8

Cross-linking can occur between a mIg and CR2 (complement receptor)

Question 9

What changes does a B cell undergo after binding Ag w/ two BCRs? 11

Answer 9

Expression of survival proteins

Increased B7 expression

Increase cytokine receptor expression

Increased CCR7 expression (integrin)

Question 10

Newly activated B cells secrete low levels of what? 12

Answer 10

IgM

Question 11

In T-independent B cell activation what is lacking? 13

Answer 11

No class-switching

No memory formed

Question 12

What is the second signal for B cell activation? 14

Answer 12

CD40L - from T cell
Bound to
CD40 - from B cell
+ cytokines

Question 13

What happens first, class switching or affinity maturation in B cells? 16

Answer 13

They both happen at the same time

Question 14

After activation from T helper cell where do B cells head? 17

Answer 14

They change their chemokine receptors and head to the follicular area where germinal centers are established

Question 15

In reference to B cells, what are the two functions of T helper cytokine secretion? 18

Answer 15

To induce heavy chain class switching

Augment B cell differentiation and proliferation

Question 16

How does switch recombination happen in B cells? What causes this? 19

Answer 16

Caused by CD40:CD40L and cytokines

DNA of heavy chain is opened up and a different C region is expressed which will be a C region downstream because IgM/IgD are the first constant regions

Question 17

What is affinity maturation? 20

Answer 17

Introducing point mutations in variable regions to raise their affinity to specific Ags

Question 18

What enzyme facilitates affinity maturation (somatic hypermutation)? 20

Answer 18

AID - activation-induced deaminase

Question 19

What does activation-induced deaminase do in Somatic hypermutation? 20

Answer 19

AID converts cytosine to uracil allowing for Ape I to create ds breaks in DNA

Question 20

After a B cell is activated and undergoes somatic hypermutation how is it able to survive within the lymph node? 23

Answer 20

If they’re able to bind a follicular DC presenting they will receive survival signals

Question 21

Speaking to B cells, which recognizes protein vs polysaccharide? Which produces memory cells? 25

Answer 21

T-dependent B cells –> memory, recognizes proteins

T-independent B cells –> lack of memory, recognizes polysaccharides

Question 22

What changes does a Plasma cell make to its cluster differentiation expression? 26

Answer 22

Decrease: CD19, 20, and HLA Class II
-they aren’t APCs anymore

Increase: CD27, CD38, and CD138

Question 23

What is the effector molecule of the humoral immunity? 26

Answer 23

Abs

Question 24

How are memory B cells able to survive for such a long time period? 28

Answer 24

By expressing more Bcl-2 (anti-apoptotic protein)

Question 25

What are the surface markers for Memory B cells? 28

Answer 25

CD27 CD45R

Question 26

What happens if Ags are fully bound to secretory IgG (IgG>Ag)? 30

Answer 26

If the Fc regions of IgG binds a BCR it shuts down and inhibits the B cell Fc region bound by an Fc receptor on the B cell with a single ITIM

Question 27

What is the principle defense against extracellular pathogens? 32

Answer 27

Humoral immunity

Question 28

Which cells have Fc receptors on their cell surface? 34

Answer 28

NKs Macrophages B cells

Question 29

What is the primary Ab present in the blood? 34

Answer 29

IgG

Question 30

What Ab isotype is predominant in primary antibody response vs secondary? What about affinity? 35

Answer 30

Primary antibody response - first infection: Usually IgM>IgG with a lower average affinity Secondary antibody response - second infection: Usually >IgG (IgA or IgE) with a higher average affinity

Question 31

What are the effector functions of Abs? 36

Answer 31

Neutralizes microbes and toxins Opsonization & phagocytosis Ab-dependent cellular cytotoxicity (NKs) Inflammation Lysis of microbes

Question 32

What two distinct functions does the Fc region serve? 37

Answer 32

It delivers Ab to inaccessible anatomical sites Serve as a bridge between Ag and Effector cells for that Ags destruction

Question 33

What do C3b and IgG have in common? 38

Answer 33

Both act as opsonizer

Question 34

What FcRs have high affinity for Ig? What cells would these receptors be found on? 39

Answer 34

FcγRI (CD64) --> Macrophages, neutrophils, eosinophils FcεRI --> mast cells, basophils, eosinophils

Question 35

What is Ab neutralization? 40

Answer 35

The idea that Abs can inhibit toxins and microbes simply by binding to them and stopping them from: Binding receptors Moving through membranes

Question 36

How does complement fulfill the role of waste management? 42

Answer 36

Erythrocytes bind immune complexes containing C3b and C4b with its CR1 receptor Erythrocyte heads to spleen and liver Phagocytes within liver and spleen remove complexes and RBC re-enters circulation

Question 37

What transports IgG from maternal circulation, across the placenta, into fetal circulation? 50

Answer 37

IgG Fc receptor bound by FcRn of the endothelial cell

Question 38

What's the difference if the first signal for B cell activation comes from two membrane Igs or a membrane Ig and CR2? 10

Answer 38

If C3d (from C3b) binds CR2 and causes complement cross-linking the attached Ag will be 1000x more immunogenic (aka better activation of the immune system)

Question 38

What is one major way Abs resemble complement? 38

Answer 38

Abs bound to Ag can be bound by FcRs to act as opsonizers

Question 39

What FcRs have low affinity for Ig? 39

Answer 39

FcγRIIA (CD32) FcγRIIB (CD32) FcγRIIIA (CD16) - NK cells (Ab-dep. cellular cytotoxicity - ADCC)

Question 40

What does ADCC stand for? What state/condition is the body in when ADCC is active? 43

Answer 40

Antibody-dependent cellular cytotoxicity Active when the body is in an anti-viral state

Question 41

What is the most effective fixer of complement (C')? Why? 44

Answer 41

IgM becuase it contains five Fc regions that can be bound by CR receptors

Question 42

What is the therapeutic role of IVIg? How does it serve this role? 45

Answer 42

In treating autoimmune/inflammatory disease Engages the inhibitory FcγRIIB (B cell) and the FcR of DCs suppressing the immune response

Question 43

What two Abs are lacking at birth and have a lag time of 6-12 months leaving the infant immunocompetent? 51

Answer 43

IgG and IgA (newly synthesized)

Question 44

What are three mechanisms of humoral immune evasion? 52

Answer 44

Ag variation - Ag not recognized Inhibition of C' Blocking via Hyaluronic acid capsule