Lecture # 20 B Cell Activation and Effector Function

Question 1

Why do CD8 cells require more co-stimulation?

Answer 1

Because they are destructive

Question 2

LFA-1

Answer 2

Receptor on the surface of T cells, binds to ICAM-1 on an infected cell or APC

Question 3

Immunological synapse

Answer 3

The point of contact between a CD8+ cell and its APC; outer ring adhesion molecules; inner ring: signaling molecules. granules behind the synapse align with cytoskeleton once binding occurs

Question 4

What are the two compounds that CD8 cell produce to induce apoptosis?

Answer 4

Perforin and Granzymes

Question 5

Perforin

Answer 5

Pore forming protein-aids in delivering contents of granules into the target cells

Question 6

Granzymes

Answer 6

serine proteases-activate apoptosis once inside the target cell; activate caspases–GrB cleaves and activates caspase 3; acts on mitochondrial proteins and eventually activates CAD that fragments DNA and leads to cell death.

Question 7

Serglycin

Answer 7

a part of the perforin/granzyme complex; may play an important role in protecting the CD8 cell from damage.

Question 8

What dictates follicular B Cell location in the LN?

Answer 8

The expression of CXCL13 and CXCR5.

Question 9

How many signals do B cells require for full activation?

Answer 9

Two signals: Signal #1 T microbial antigen binding to BCR; #2 PRR engagement or complement by R (PRR engagement is T independent) T dependent require interaction with CD40L

Question 10

Thymus Independent Responses type 1

Answer 10

TI-1; some TI-1 antigens are called B cell mitogens; LPS can induce polyclonal activation, non specific antibodies at high concentrations-activates TLR4

Question 11

Thymus Independent Responses type 2

Answer 11

TI-2; Ags are characterized by having multiple identical epitopes: polysaccharides; B1 cells and marginal zone B cells important for TI-2 responses;Usually IgM produced but some cases switching to IgG

Question 12

What is signal # 2 for T-dependent Antigens?

Answer 12

Signal 2 is provided by CD40:CD40L and cytokines

Question 13

CXCR5

Answer 13

Present on lymphocytes. Is up-regulated after CCR7 is down-regulated;purpose is to aid in migration to the follicle; is a receptor for CXCL13 (chemokine)

Question 14

Ki67

Answer 14

proliferating cell marker (centroblasts); present on actively proliferating B cells

Question 15

FDC (anti-CD3)

Answer 15

Help to retain Ag in the GC secretes CXC13;

Question 16

What happens as B-Cells move through GCs?

Answer 16

they undergo somatic hypermutation, affinity maturation and isotype switching

Question 17

IgM function

Answer 17

Complement activation

Question 18

IgG function

Answer 18

opsonization, phagocytosis, complement activation, neonatal immunity

Question 19

IgE, IgG4 function

Answer 19

Immunity against helminths, mast cell degranulation (immediate hypersensitivity); Th2 cell induced

Question 20

IgA function

Answer 20

mucosal immunity (transport of IgA through epithelia)

Question 21

Receptors on B cell (for T cell interaction)

Answer 21

(B7-1 and B7-2); CD40; MHC II or I

Question 22

Receptors on T cell (for B cell interaction)

Answer 22

(CD28 reacts with B7-1/2) CD40L

Question 23

Class switching

Answer 23

Activated by cytokines inducing transcription of switch region upstream of C region; lies in intron b/w J region and C u and upstream of all other C genes; Th1-> IgG1, IgG3, while Th2 -> IgG4 and IgE

Question 24

Process of class switching

Answer 24

Occurs after B cells encounter Ag; RNA-DNA hybrids for in the switch region; AID (activation induced cytidine deaminase) converts cytidine to uracil; UNG removes the uracil leaving abasic sites APE1 cleaves abasic sites leaving a nick in the DNA, ds breaks are repaired by normal ds break repair mechanisms.

Question 25

Somatic Hypermutation

Answer 25

mechanism to induce point mutation in the V regions of existing BCR; mutations occur 1000x; AID also plays a huge role; result is a multitude of B cells with different affinity receptors. Those BCRs that bind with high affinity receive survival signals. (selection occurs by follicular DCs)

Question 26

Where do the point mutations in somatic hypermutation accumulate?

Answer 26

Point mutations accumulate in the BCRs of the VH and VL chains.

Question 27

Which Co-receptor is necessary for the Th activation?

Answer 27

CD28 not CTLA-4 binds to B7-1/B7-2 for activation. CTLA-4 binds to B7-1/2 with higher affinity and tells the cell to stop proliferating and limits the binding of CD28 and B7-1/2

Question 28

CTL binding and destruction of target cells depends on:

Answer 28

antigen presentation on the surface of the target cells.

Question 29

Antigen binds to T cells first and divide in response to IL-2 and then differentiate into effector helper or cytotoxic cells (T/F)

Answer 29

T (CD8 and CD4 proliferate in repsonse to IL-2) and then other cytokines cause differentiation

Question 30

Only viral or bacterial infected cells are susceptible to CTL-mediated apoptosis (T/F)

Answer 30

T (CTL-mediated apoptosis only occurs on virally infected cells; non-infected cells are spared)

Question 31

Conventional DCs secrete high levels of IFN-b in response to viral infection (T/F)

Answer 31

F CDCs secrete IL-12; uptake antigen; migrate from sites from infection to lymph nodes; involved in presentation