Lecture 13

Question 1

Describe the percentage of total T cells in the blood that the following T cell types are responsible for.

Helper T cells:

Cytotoxic T cells:

Answer 1

Helper T cells: 66%
(have TCR and CD4 markers)

Cytotoxic T cells: 33%
(Have TCR and CD8 markers)

Question 2

CD8+ T cells are class ___ MHC-restricted. Explain what Naive CD8+ T cells recognize and where this recognition occurs.

Answer 2

CD8+ T cells are class 1 MHC-restricted

Naive CD8+ T cells recognize peptide Ags that are presented by DC’s in the lymph nodes

Question 3

After a naive CD8+ T cell is activated, where does it go and what does it do?

Answer 3

Activated CD8+ T cells enter circulation in order to migrate to the the site of Ag acquisition

Then they recognize the Ag in the tissue and “kill the target cells where the Ag is being produced”.

Question 4

Naive CD8+ cells require 2 signals in order to become an effector CTL. State these 2 signals.

Answer 4

1. recognition of Ag

2. CD28-CD80 costimulation

Question 5

Which cell contains granules full of perforin and granzymes to kill other cells? what macrophage-stimulating cytokine do these cells secrete? lastly, which transcription factor regulates the genetic expression of this cell type?

Answer 5

CTL’s

They secrete IFN-gamma (to recruit macrophages to come clean up the mess the CTL’s make)

Transcriptional factor T-bet

Question 6

True or False:

CTL’s will not be recognize antigens that are presented through peptides of the Class II MHC. explain.

Answer 6

False

While CTL’s normally react to antigens that are presented through the Class I MHC, “Cross-presentation” is a method by which Class II MHC presentation can still activate a CTL.

After and extracellular (usually isn’t a CTL antigen) antigen is phagocytosed into a DC, some of the antigen can leak out into the cytoplasm of the DC and are then presented through the class I MHC process (NOW CTL’s react)

Question 7

CD4+ Effector cells react about 2 days prior to CD8+ cells react. Explain why.

Answer 7

DC cells, which are crucial for CD8+ effector cells to recognize antigens, need time to be “licensed/educated”

Question 8

Explain the mechanism of DC cell licensing

Answer 8

A CD4+ T cell (which has already been activated by a different DC cell via the TCR/MHCII complex) provides the first signal (1) through CD40L/CD40 signaling

The same CD4+ T cell will also give the second signal (2) via IFN-gamma production

The CD40L/CD40 and IFN-gamma signals upregulate CD80/CD86 in the DC cell in order to increase cross-presentation activity in the DC
(this allows the DC to effectively stimulate CD8+ cells)

Question 9

Compare the levels of responses in terms of their strength based on the 3 following scenarios: (which of these is considered to be a licenced DC?)

1. DC secretes IL-12 (IL-15 also works) AND DC costimulates a CD8+ T cell
2. CD4+ secretes IL-2 AN DC costimulates a CD8+ T cell
3. CD4+ secretes IFN-gamma (and the DC secretes IL-12) AND enhances the ability of the DC to stimulate CTL differentiation

Answer 9

1. Low activation level (suboptimal response)
2. Moderate activation level (potentiated response)
3. Highest activation level (potentiated response)

Question 10

Describe the function of the following cytokine:

IL-2:

Answer 10

IL-2: promotes proliferation/differentiation of CD8+ T cells (NOT naive CD8+ cells) into CTL’s and effector cells

Question 11

Describe the function of the following cytokine:

IL-12 and IFN-gamma:

Answer 11

IL-12 and IFN-gamma: stimulate the “differentiation” (not proliferation) of NAIVE CD8+ T cells into CTLs

(Naive CD8+ T cells proliferate in response to TCR and CD28 signals but NEED IL-12 or IFN-gamma to develop effector functions)

Question 12

Describe the function of the following cytokine and what cells make it.

IL-15:

Answer 12

IL-15: stimulates the survival of memory CD8+ T cells

it is produced by DC’s and Resident tissue macrophages

Question 13

Describe the function of the following cytokine and what cells make it

IL-21:

Answer 13

IL-21: plays a role in the induction of CD8+ memory cells and prevention of “T cell exhaustion” (plays a potentiating role in many cells)

it is produced by activated CD4+ T cells

Question 14

What 2 cytokines share a gamma chain with IL-2 and can therefore activate the IL-2 receptor on activated CD8+ T cells?

Answer 14

IL-15 and IL-21

Question 15

Which cytokine has a key feature of an “autocrine loop” process where it causes CD4+ T cells basically up regulate the production of itself and its receptors? Describe the paracrine type of signaling that this cytokine can conduct as well.

Answer 15

IL-2

IL-2 secreted by CD4+ cells can activate nearby CD8+ cells
para = affects other cells ; auto = affects its own cells

Question 16

Which Cytokine is a potent activator of resident tissue macrophages and is released by Th1 cells, CTL’s and activated NK cells? This cytokine favors the development of Th1 cells, which causes B cells to undergo class switching from which 2 antibodies?

Answer 16

IFN-gamma

It causes class switching away from IgE and towards IgG

Question 17

IFN-gamma can increase the expression of Class I MHC molecules and the expression of Class II MHC molecules in APC’s ONLY. Why might this occur?

Answer 17

It is an important component of antiviral protection.

(since it up regulates the Ag presentation of viral targets within an infected cell ; makes intracellular Ag’s stand out more)

Question 18

When IFN-gamma causes B cells to conduct class switching from IgE to IgG, what might an advantage of this be?

Answer 18

IgG (compared to IgE which is more involved with mast cell degranulation) is much more specific and effectively enhances the responses of phagocytes to its corresponding the Ag

Question 19

True or False:

B cells, like all other APC’s, secrete IL-12 in order to stimulate CD4+ T cells after the CD4+ T cell has activated it with an Ag. explain.

Answer 19

False

only Professional APC’s (DCs and resident tissue macrophages) produce IL-12 after they are activated by a CD4+ T cell.

(B cell’s are “selfish” and “forget” about CD4+ T cells after they have be activated, while DCs and Resident tissue macrophages return the favor to CD4+ T cells by secreting IL-12)

Question 20

Describe the relationship between IL-12, IFN-gamma, and TNF-Beta.

Answer 20

IL-12 stimulates the production of proinflammatory cytokines (IFN-gamma and TNF-beta) by CD4+ and CD8+ T cells

Question 21

State the 2 main effects that IL-12 stimulated CD8+ T cells have when compared to CD8+ T cells that are stimulated by IFN-gamma

Answer 21

IL-12 CD8+ T cells are more effective in “controlling tumors” (bc they will maintain higher numbers/function)

And IL-12 prevents CD8+ T “cell exhaustion”

Question 22

True or False:

IL-12 activates NK cells. explain.

Answer 22

True

doesn’t need to be explained

Question 23

Name 2 cytokines with very similar biological properties and then state which subunit of theirs is different from one another.

Answer 23

IL-12 and IL-15 have similar biological properties

IL-12 and IL-15 have the SAME Beta subunit but DIFFERENT alpha subunits

Question 24

Which cell does IL-15 have more of an affect on, CD8+ or Cd4+ T cells? describe how IL-15 serves as a chemoattractant in human blood.

Answer 24

CD8+ T cells

T cells will follow IL-15 gradient’s to the area of highest concentration in human blood (like a shark smelling blood)

Question 25

State the adaptive immunity cell types that IL-21 stimulates a potentiating response (IL-21 is always a potentiating response, not inhibitory but there are 5 cell types to be listed here)

Answer 25

CD4 cells CD8 cells Tfh cells Th17 cells NKT cells

Question 26

Which cytokine is a well known pleiotropic cytokine? what types of diseases can high levels of this cytokine cause?

Answer 26

IL-21 Autoimmune diseases (clinical trials on IL-21 inhibitors to treat autoimmune diseases have begun)

Question 27

True or False: IL-21 ALONE has been found to effectively treat solid tumors. explain.

Answer 27

True IL-21 alone or in combination with other cytokines has been shown to effectively treat solid tumors

Question 28

In an acute viral infection, CD8+ T cells differentiate into what type of cell in order to eliminate the infected cells?

Answer 28

CTL's

Question 29

Briefly describe the role of CD8+ and CD4+ T cells in a viral infection

Answer 29

CD8+ T cells produce chemokines and cytokines in order to eliminate virally infected cells (dunks the oop ; Lebron) CD4+ T cells help to stimulate CD8+ T cells and DC's (throws the oop ; D Wade)

Question 30

Explain the significance of PD1 and CTLA-4 in terms of their relationship to CTLs (which are CD8+ T cells). How is this related to CD8+ T cell exhaustion?

Answer 30

PD-1 and CTLA-4 are inhibitory signals that block the activation of CTLs Exhausted CD8+ T cells show reduced production of IFN-gamma and increased expression of PD-1 inhibitory receptors

Question 31

What is it called when the initial responses of CD8+ T cells are initiated but then gradually decline in a chronic viral infection such as HIV or Hepatitis C?

Answer 31

cell exhaustion

Question 32

Compare the FasL mediated apoptosis and Granzyme mediated apoptosis mechanisms that CTL's can conduct

Answer 32

BOTH begin by the formation of the immunological synapse between the cytotoxic T cell and the target cell FasL mediated apoptosis: FasL is expressed on activated CTLs and engages with the Fas (receptor) on the target cell to signal for apoptosis to occur Granzyme mediated apoptosis: the CTL releases complexes of perforin, which penetrates the target cell PM to allow granzymes to enter and granzymes that trigger apoptosis once inside the cytoplasm of the target cell

Question 33

Type I cells such as thymocytes and Type II cells such as virus-infected cells carry out Fas-FasL apoptosis via different mechanisms. Describe each of these.

Answer 33

Type I cells: Mito independent Caspase 8 DIRECTLY cleaves Caspase 3 Caspase 3 degrades ICAD (inhibitor of caspase-activated DNase) which allows CAD to degrade DNA and begin apoptosis Type II cells: Mito dependent Caspase 8 cleaves Bid which causes cytochrome C release from the mito Cytochrome C, Apaf-1, and ATP work together to activate Caspase 9, which then activates Caspase 3 Caspase 3 degrades ICAD (inhibitor of caspase-activated DNase) which allows CAD to degrade DNA and begin apoptosis

Question 34

Which apoptosis type was discovered by studying the type of apoptosis that occurs during embryologic changes in humans and is known as the "clean way" bc there is no inflammation that occurs?

Answer 34

Type I apoptosis (mito independent)

Question 35

True or False: During granzyme-mediated apoptosis, granzymes and perforins are only released in the area of the immunological synapse so that only the target cell and CTL are damaged. explain.

Answer 35

False Yes, granzymes and perforins are only released in the area of the synapse (this process cannot occur without the formation of the immunological synapse) to prevent them from causing random damage. CTL's are not damaged by granzyme-mediated apoptosis, only the target cell is

Question 36

Granzymes A, B, and C are all serine proteases that are released by CTL's. Which of these is REQUIRED for CTL cytotoxicity and what exactly does it do once it enters the target cell?

Answer 36

Granzyme B once inside the target cell, Granzyme B activates Caspase 3 to induce apoptosis.

Question 37

Perforin is a membrane-preturbing molecule that is homologous to which complement protein? Explain the mechanism by which perforin insertion in the membrane of a target cell occurs

Answer 37

C9 Perforin insertion causes a compensatory membrane repair process that leads to the internalization of BOTH perforin and granzymes