Exam 2: Dr. Pinchuk T-cell Mediated Immunity 2

Question 1

What does the third signal for Tc cell activation come from?

Answer 1

The APC in the form of IL-12

The cytokine strongly directs immune responses toward CD8-Tc cell response

Question 2

What are cytotoxins? Examples?

Answer 2

Protein in the granules of cytotoxic T cells

Perforin, granzymes, and granulysin

Question 3

What is the action of perforin on target cells?

Answer 3

Aids in delivering contents of granules into the cytoplasm of target cell

Question 4

What is the action of granzymes on target cells?

Answer 4

Serine proteases, which activate apoptosis once in the cytoplasm if the target cells

Question 5

What is the action of granulysin on target cells?

Answer 5

It has antimicrobial action and it can induce apoptosis

Question 6

What cytokines can cytotoxins produce?

Answer 6

IFN-γ
LT-α
TNF-α

Question 7

Because cytotoxins can produce cytokines, what does that men?

Answer 7

Cytotoxins can activate macrophages

Question 8

What happens upon specific antigen recognition by cytotoxic T cells to cytotoxins?

Answer 8

The delivery of cytotoxins is aimed directly at the target cell

Question 9

What is the life cycle of a Tc cell?

Answer 9

Naive CD8 T cell has antien recognition and goes through activation. Then, there is clonal expansion. These all occur in lymphoid organs. After that, the cell differentiates into a memory CD8 T cell or effector CD8 T cell in peripheral tissues.

Question 10

What are the effector functions of the effector CD8 T cell?

Answer 10

Killing of infected target cells

Macrophage activation

Question 11

What must T cells see in order to perform effector function?

Answer 11

Self-MHC

Question 12

What are cytotoxic T cells?

Answer 12

Selective and serial killers of target cells

Question 13

How does a cytotoxic T cell kill a target cell?

Answer 13

CTL recognizes virus-infected
CTL programs target cell to die
CTL moves to another target cell
First target cell dies

Question 14

What is apoptotic cell death?

Answer 14

Programmed cell death

Question 15

What T cells become natural regulatory T cells?

Answer 15

T cells specific for self antigen recognized in the thymus

Question 16

What T cells become induced regulatory T cells?

Answer 16

T cells specific for self or commensal microbiota antigen recognized in presence of TGF-β in the periphery

Question 17

What do cytokines produced by Treg cells do?

Answer 17

Inhibit other self-reactive T cells

Question 18

What makes up regulatory T cells?

Answer 18

FOXP3+ CD4+ CD25+ Tregs

Question 19

What do regulatory T cells do?

Answer 19

Suppress the proliferation and IL-2 production of naive cells
Could suppress CD4 and CD8 cells

Question 20

What are the effector mechanisms of Tregs

Answer 20

Surface molecules have a constitutive expression of CTLA-4 which suppresses autoreactive T cells
Cytokines, IL-10, TGF-β are potent immunomodulatory cytokine that have anti-inflammatory function
Cytotoxins, perforin, gransyme A, and Fas-FasL

Question 21

What does CTLA-4 bind?

Answer 21

B7-1 and B7-2

Question 22

What is IL-10?

Answer 22

Potent immunomodulatory cytokine

Question 23

What are functions of IL-10?

Answer 23

Anti-inflammatory*
Down-regulates production of Th1-type cytokines
Decreases the expression of MHC class II and co-stimulatory molecules on DCs (tolerogenic state)*
Regulates the activation and function of mast cells
Regulates cytokine production by eosinophils
Directly suppresses T cell proliferation*

Question 24

What is the triadic function of TGF-β?

Answer 24

Acts as a SWORD to paralyze cell activation and differentiation to suppress immune response
Acts as a WAND to convert naive T cells into iTregs and Th17 to aid in their combat against inflammation and infection
Acts as a SHIELD to protect and maintain Tregs against apoptosis and destabilization when surrounded by inflammation and consistent stimulation

Question 25

What is the physiologic role of Th17 cells in the immune system?

Answer 25

Protective function against microbial pathogens

Question 26

What do Th17 cells represent?

Answer 26

A pro-inflammatory subset that contributes to autoimmunity and tissue damage

Question 27

What is the non-pathogenic subset of Th17 cells incapable of?

Answer 27

Promoting autoimmune inflammation and might even act anti-inflammatory

Question 28

What are highly pathogenic Th17 cells from?

Answer 28

Naive precursor cells that occur independently of TGF-β signaling in the presence of IL-23, IL-6, and IL-1β

Question 29

What is the function of Th17 cells?

Answer 29

To attract neutrophils and monocytes

Question 30

What are the Th17 and Treg developmental pathways like?

Answer 30

Reciprocally interconnected implicating a balance between both cell types which influences the outcome of the immune response

Question 31

What does the shared requirement of TGF-β and reciprocal regulation of the transcription factor between Th17 and Tregs provide?

Answer 31

Phenotypic and functional plasticity in both populations allowing differentiated cells to re-differentiate

Question 32

What kind of effect do Tregs have?

Answer 32

An antagonistic effect, which in failure contributes to the same diseases as excess Th17

Question 33

What does the Th17/Treg balance provide?

Answer 33

A basis for understanding the immunological mechanisms that induce and regulate autoimmunity and chronic inflammation

Question 34

When does inflammation occur?

Answer 34

FOXP3 is blocked by IL-6 and IL-21 which causes more Tregs (FOXP3)

Question 35

When does tolerance occur?

Answer 35

FOXP3 inhibits the expression of RORc causing Tregs and Th17 to be balanced

Question 36

When are T cells anergic?

Answer 36

In the absence of the co-stimulatory signal

Question 37

What are the immunologically privileged sites?

Answer 37

``` Brain Eye Testis Uterus (fetus) Hamster cheek pouch ```

Question 38

What is the most import form of tolerance?

Answer 38

Non-reactivity to self antigens

Question 39

What is it called when an antigen induces tolerance?

Answer 39

Tolerogen

Question 40

Describe cyctotoxic T cells

Answer 40

CD8 T cells | Kill infected cells by inducing apoptosis

Question 41

What is Th17 involved with?

Answer 41

Inflammation

Question 42

What do Tregs do?`

Answer 42

Either kill DCs or make them tolerogenic

Question 43

What are the mechanisms of central tolerance?

Answer 43

Negative selection in the thymus | Autoimmune regulator

Question 44

What are mechanisms of peripheral tolerance?

Answer 44

Absence of co-stimulatory signal Immunological privileged sites Regulatory T cells