Exam 3: Costimulation, T Cell Anergy, Immunological. Synapse

Question 1

What are the two MHC restriction paradoxes?

Answer 1

Alloreactivity and Superantigens

Question 2

Describe alloreactivity

Answer 2

When foreign MHC complex is recognized by T cells (1-10% od T cells react this way). T cells view very similar structure (whether peptide dominant or MHC dominant)

Question 3

Describe superantigens

Answer 3

bacterial and viral proteins that can activate 2-20% of all T cells (all T cells expressing VB gene segments)

Question 4

Bacterial superantigens are responsible for

Answer 4

toxic shock syndrome

Question 5

Do superantigens need to be processed?

Answer 5

No

Question 6

T/F Superantigens are Class I dependent

Answer 6

F. They are Class II dependent

Question 7

Where to superantigens bind??

Answer 7

Outside of groove in MHC/TCR complex

Question 8

What is an example of a bacterial superantigen?

Answer 8

Staphylococcal enterotoxin (SE); TSST-1

Question 9

What is the difference between bacterial and viral superantigens?

Answer 9

Viral superantigens (often from retroviruses) are membrane bound (APC cell membrane); bacterial are soluble

Question 10

Signal 1

Answer 10

TCR and MHC –> antigen-specific

Question 11

Signal 2

Answer 11

Co-stimulation from antigen-independent receptor

Question 12

Where are costimulatory molecules expressed?

Answer 12

APC’s

Question 13

What are adjuvants?

Answer 13

substance that induce APC to upregulate ligands for co-stim receptors on T cells

Question 14

What is the most important co-stim molecule expressed on T cells?

Answer 14

CD28!!!

Question 15

3 properties of CD28

Answer 15

1. member of immunoglobulin superfamily (IgV domain)
2. Expressed on almost all T cells (all mouse cells; 80% of human T cells) as a disulfide-linked dimer
3. Binds to B7-1 (CD80) and B7-2 (CD86) expressed on APC’s (also Ig superfamily members containing one IgV and one IgC domain)

Question 16

B7-1 is also called

Answer 16

CD80

Question 17

B7-2 is also called

Answer 17

CD86

Question 18

What happens when TCR and costimulatory signals are seen?

Answer 18

proliferation and IL-2 production; followed by self-signaling via IL-2

Question 19

Name the 3 binding motifs associated with CD28

Answer 19

1. PI3K
2. Grb2
3. Irk
   NO ITAM

Question 20

what happens when CD28 is the only signal

Answer 20

Nothing except for activation of PI3K

Question 21

What are some other costimulatory molecules?

Answer 21

ICOS; CD40; 4-1BB

Question 22

T/F ICOS is expressed after activation of naive T cells

Answer 22

T

Question 23

What induces ICOS signal?

Answer 23

CD28 costimulation!

Question 24

What does ICOS bind to?

Answer 24

LICOS aka ICOSL aka B7RP-1

Question 25

What is ICOS important for?

Answer 25

IL-4 production

Question 26

APC or T cell | CD40, 4-1BBL

Answer 26

APC

Question 27

APC or T cell | CD40L, 4-1BB

Answer 27

T cell

Question 28

How are CD40/CD40L and 4-1BB/4-1BBL and ICOS/LICOS similar?

Answer 28

Help define differentiation of T cell determine which cytokines are used effector or memory cells sustain T cell activation

Question 29

CD28 initiates activation, ICOS, CD40, 4-1BB ___

Answer 29

FINE TUNE response

Question 30

Name an inhibitory co-stimulatory molecule

Answer 30

CTLA-4

Question 31

How does CTLA-4 inhibit activation?

Answer 31

outcompetes CD28 and binds to B7-1 and B7-2

Question 32

Why do we need CTLA-4

Answer 32

negative feedback helps prevent too much of an immune response. CTLA-4 amounts high after TCR + CD28 stimulation.

Question 33

What induces CTLA-4 expression?

Answer 33

activation of naive T cells over time when balance is tipped. Allows immune system to shut down when pathogen is mostly cleared

Question 34

What is the inactive/tolerant state when T cells are activated without costim?

Answer 34

ANERGY

Question 35

Why do we have anergenic T cells?

Answer 35

damp down autoimmune reactions; regulatory type T cells

Question 36

What two things are required for Immunologic Synapse that facilitates T cell response to APC/target cell?

Answer 36

1. Reorganization of the T cell to have organelles facing APC 2. Lipid raft reorganization so small lipid rafts condense to form larger lipid rafts to facilitate adhesion molecules (ICAM) to provide signaling complex

Question 37

What molecules facilitate reorganization of T cell?

Answer 37

Vav- a GED | WASp--> activates Arp2/3 complex --> critical for actin cytoskeleton reorientation