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

1
Q

What are the two MHC restriction paradoxes?

A

Alloreactivity and Superantigens

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2
Q

Describe alloreactivity

A

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)

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3
Q

Describe superantigens

A

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

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4
Q

Bacterial superantigens are responsible for

A

toxic shock syndrome

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5
Q

Do superantigens need to be processed?

A

No

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6
Q

T/F Superantigens are Class I dependent

A

F. They are Class II dependent

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7
Q

Where to superantigens bind??

A

Outside of groove in MHC/TCR complex

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8
Q

What is an example of a bacterial superantigen?

A

Staphylococcal enterotoxin (SE); TSST-1

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9
Q

What is the difference between bacterial and viral superantigens?

A

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

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10
Q

Signal 1

A

TCR and MHC –> antigen-specific

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11
Q

Signal 2

A

Co-stimulation from antigen-independent receptor

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12
Q

Where are costimulatory molecules expressed?

A

APC’s

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13
Q

What are adjuvants?

A

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

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14
Q

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

A

CD28!!!

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15
Q

3 properties of CD28

A
  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)
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16
Q

B7-1 is also called

A

CD80

17
Q

B7-2 is also called

A

CD86

18
Q

What happens when TCR and costimulatory signals are seen?

A

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

19
Q

Name the 3 binding motifs associated with CD28

A
  1. PI3K
  2. Grb2
  3. Irk
    NO ITAM
20
Q

what happens when CD28 is the only signal

A

Nothing except for activation of PI3K

21
Q

What are some other costimulatory molecules?

A

ICOS; CD40; 4-1BB

22
Q

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

A

T

23
Q

What induces ICOS signal?

A

CD28 costimulation!

24
Q

What does ICOS bind to?

A

LICOS aka ICOSL aka B7RP-1

25
Q

What is ICOS important for?

A

IL-4 production

26
Q

APC or T cell

CD40, 4-1BBL

A

APC

27
Q

APC or T cell

CD40L, 4-1BB

A

T cell

28
Q

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

A

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

29
Q

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

A

FINE TUNE response

30
Q

Name an inhibitory co-stimulatory molecule

A

CTLA-4

31
Q

How does CTLA-4 inhibit activation?

A

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

32
Q

Why do we need CTLA-4

A

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

33
Q

What induces CTLA-4 expression?

A

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

34
Q

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

A

ANERGY

35
Q

Why do we have anergenic T cells?

A

damp down autoimmune reactions; regulatory type T cells

36
Q

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

A
  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
37
Q

What molecules facilitate reorganization of T cell?

A

Vav- a GED

WASp–> activates Arp2/3 complex –> critical for actin cytoskeleton reorientation