Lecture 9: Activation of T Lymphocytes

Question 1

The proliferation of T lympohcytes and their differentiation into effector and memory cells reuires what three signals

Answer 1

• Ag recognition (signal 1)
• Costimulation (signal 2)
• Cytokines (signal 3)

Question 2

Activation of naive T cells requires recognition of Ag presented by ____ meanwhile effector T cells can recognize Ags presented by ____ and _____

Answer 2

Naive T cells require DCs

Effector T cells can recognize Ags presented by Tissue macrophages and B cells

Question 3

Superantigens (Sags) bind simultaneously

Answer 3

• MHC class II molecules (not in the peptide-binding groove) and the V region of the beta subunit of the TCR
• this leads to T cells produce massive amounts of cytokines (such as TNF-alpha, IL-1beta, and IL-2) which may lead to shock

Question 4

The best characterized costimulatory pathway in T cell acitvation

Answer 4

• T cell surface receptor CD28
• binds costimulatory molecules B7-1 (CD80) and B7-2 (CD86) expressed on activated APCs
• B7 costimulators are regulated and ensure that T lympocyte responses are initiated only when needed.

Question 5

CTLA-4-mediated immune checkpoint is induced in naive T cells at the time

Answer 5

of their intial response to Ag

Question 6

The stronger the stimulation through the TCR and CD28 the greater the amount of ___ that is deposited on the T cell surface from the inracellular vesicles

Answer 6

CTLA4

Question 7

Inflammatory signals in the tissues have what effect on expression of PD1 ligands

Answer 7

• induce expression of PD1
• this is a way to downregulate the activity of T cells and thus limit collateral tissue damage in response to a microorganism infection in that tissue.

Question 8

Question 9

Question 10

Question 11

Question 12

No other cytokine can replace ____ for the mainenance of functional Treg cells

Answer 12

IL-2

Question 13

CD69 binds to and reduces surface expression fo the ________ receptor _____

Answer 13

• Sphingosine-1-phosphate receptor S1PR1
• as a result, activated T cells are retained in the LNs long enough to receive the signals that initiate their proliferation and differentiation into effector and memory cells

Question 14

IL-2Ralpha is also known as CD___

Answer 14

CD25

Question 15

What are the inhibitory receptors on T cells

Answer 15

• CTLA4
• PD-1

Question 16

various regulatory mechanisms contribute to the normal contraction of T cells, such as:

Answer 16

• The inhibitory receptors CTLA4 and PD-1
• Apoptosis induced by death receptors TNFRI and Fas
• Treg cells
• (not that IL-2 secretion decreases as well)

Question 17

The vast majority of memory T cells reside in

Answer 17

tissue sites, including lymphoid tissues, intestines, lungs and skin

Question 18

What transcription factor promotes the generation of T memory cells

Answer 18

Blimp-1

Question 19

The number of memory T cells specific for any Ag is ____ than the number of naive cells specific for the same Ag

Answer 19

greater (typically 10-100 fold more than the pool of naive cells)

Question 20

What cytokines induce the expression of anti-apototic proteins and stimulate low-level proliferation of memory cells

Answer 20

IL-7 and IL-15

Question 21

memory T cells pass through what three distinct phases

Answer 21

• Memory generation
• memory homeostasis
• immunosenescence

Question 22

What are the phenotypic markers for memory T cells

Answer 22

• IL-7R
• CD45
• CD27

Question 23

The central memory T cells (T_cmcells) express the chemokine receptor ____ and _____ and home mainly to

Answer 23

• The central memory T cells (T_cmcells) express the chemokine receptor CCR7 and L-selectin and home mainly to LNs, spleen, and circulate in the blood
  
  • Proliferate (high production of IL-2) and generate many effector cells on Ag challenge

Question 24

Effector memory T cells (T_EMcells) circulate in the blood. They do not proliferate but produce

Answer 24

• IFN-gamma and TNF or become cytotoxic

Question 25

Resident tissue memory T cells (T_RMcells) reside in epithelial barrier tissues at the interface between the host and environment. They produce

Answer 25

IFN-gamma and TNF and are specific for pathogens and other Ags that have been encountered previously though that barrier epithelium

Question 26

Question 27

CD69 binds to and reduces surface expression of the

Answer 27

• sphingosin 1-phosphate receptor (S1PR1)
  
  • As a result, activated T cells are retained in the LNs long enough to receive the signals that initiate their proliferation and differentiation into effector and memory cells

Question 28

Expression of CD40L (CD154) is highly increased in activated T cells within ___ to ___ hours after Ag recognition

Answer 28

• 24-48 hours