T-cell Immunity

Question 1

Kinetics to T cell response

Answer 1

Pathogen introduced, initially have NAIVE TCs that have not recognized Ag and have not become activated

• once recognition occurs–>clonal expansion occurs
• now have high #’s of TCs specific for Ag
• They undergo EFFECTOR response
• Once no longer needed they decline and only a few remain as memory cells

Question 2

What do DC do?

Answer 2

They take up bacterial Ag in the skin and then move to enter the draining lymphatic vessel

• here DC waits in TC area of LN–> wait fro TCs that are traveling from the lymph/blood to LN
• TCs sample the DC for expression of Ag that it responds to

Question 3

What causes DC to home into LN?

Answer 3

They express receptor CCR7, and LN express ligand for receptor

Question 4

Ways DC process/present Ag

Answer 4

Multiple ways

–>can activate all effector TCs

Question 5

Naive TCs

Answer 5

If TC doesnt encounter Ag it will leave and remain in circulation until correct Ag present

Question 6

What controls migration of naive T-cells?

Answer 6

They express homing receptors

Question 7

What are the requirements for ACTIVATING naive TCs?

Answer 7

Two Signals

1. Ag recognition
2. Co-stimulatory signal –> B7(APC)-CD28(TC)
   - ->needs to be high for TC to become activated

Question 8

What occurs if only Ag recognition occurs?

Answer 8

Unresponsiveness or ANERGY

Question 9

What occurs if only co-stimulation occurs?

Answer 9

No effect

Question 10

B7

Answer 10

Expression primarily limited to APCs

Activation of APCs induces B7 expression @ high levels

Question 11

When isn’t CD28 co-stimulation not required?

Answer 11

gamma/delta TCs
CD8+ T cells
In presence of strong signal 1
High avidity responses
**EFFECTOR AND MEMORY TCs

Question 12

What are the diff APCs?

Answer 12

DC (express MHC 2), MO (MHC1), and B-cells(MHC2)

Question 13

Are all APCs equal in presenting Ag?

Answer 13

NO!
DC- activate a broad range of TCs
MO and BCs - activate effector and memory cells

Question 14

Proliferation/Differentiation of activated naive TCs is driven by?

Answer 14

IL2

• naive TCs express low affinity IL2R
• activated TCs express high affinity IL2R and secrete IL2
• binding of IL2 to high aff receptor sends signal to TC
• signal induces TC proliferation

Question 15

Do other cell surface (besides IL2) change after TC activation?

Answer 15

Yes

Question 16

What directs activated TC to distinct anatomical sites?

Answer 16

Differential expression of adhesion molecules

• receptors on TCs act as homing signals to guide TCs to diff places
• target organ will express ligand for receptor

Question 17

What are the functional classes of effected CD4+ TCs? (5)

Answer 17

They all start out as THo–>and based on environement they will differentiate into certain ones

• Th1
• Th2
• Th17
• Tfh
• Treg

Question 18

What is the importance of **CD40 ligand (TC)?

Answer 18

Critical to the ability of **CD4+ TCs to activate other cells

• • in order to have effector response and activate target they have to have a COGNATE INTERACTION
• MO–>cell mediated immunity
• BCs–>humoral immunity

Question 19

What is cognate interaction?

Answer 19

Interaction of BC with TC w/ specificity for the SAME Ag

Question 20

What controls whether CD4+ cell become Th1 or Th2?

Answer 20

Cytokine exposure after activation

Question 21

What determines the outcome of intracellular infections?

Answer 21

The balance between Th1 and Th2

-Th1 - cell mediated

Question 22

CD8+ cells are..

Answer 22

Cytotoxic TCs or CTLs

Question 23

CD8+ TCs activated?

Answer 23

Recognize Ag presented by MHC C1 and after co-stimulation they become activated and produce diff cytotoxins/cytokines

Question 24

How are **CD8+ TCs activated?

Answer 24

Activated by **CD28/B7

-may require additional help (from cytokines)

Question 25

What is the CTL killing mechanism?

Answer 25

- Granule Exocytosis is the predominant PW (FAST) - ->**granzymes and perforin - Expression of cell surface TNF-fammily effector molecules (SLOW) - Secretion of soluble toxic cytokines (SLOW)

Question 26

What is the granule exocytosis model?

Answer 26

Their is activation-induced re-orientation of granules to site of interaction - release of granzymse/perforin-->form pores - induces apoptosis in target cell

Question 27

Can CTLs kill targets in succession?

Answer 27

Yes, after killing they can disengage to kill new target cell --re-synthesis granules

Question 28

How does TC response get shut off?

Answer 28

* *Interaction w/ CTLA4-->**antagonist of CD28 turns off activation of TC - inhibitory receptor for B7 - Expressed on activated TCs

Question 29

How does CTLA4 regulate TC activation?

Answer 29

BINDS with higher affinity to B7 then CD28 does - outcompetes CD28 binding to B7 - leads to anergy

Question 30

What can occur if defect in CTLA4?

Answer 30

Autoimmune diseases

Question 31

What are some additional factors in ending the TC response?

Answer 31

Elimination of Ag Elimination of other stimuli T reg cells - express CTLA4 Killing by immunoregulatory cells - shrinking TC pop so only memory cells remain