L17_T-Cell Immunity

Question 1

What two signals does a naive T-cell need on a regular basis to stay alive?

Answer 1

Just a “tickle” from self MHC receptors (This wont be a strong binding because the TCR should not bind the self peptide strongly). Also all naive T-Cell express IL-7 receptor and this needs to be stimulated by IL 7 which is bound to the extra cellular matrix

Question 2

Describe the accessory molecules that help control routes of T Cell migration.

Answer 2

Selectins, integrins, and chemokine receptors control th emigration of naive t-cells in and out of lymph nodes and of effector and memory t-cell to sites of infection

Question 3

Describe how accessory molecules help strengthen the adhesion of T-cells to APCs and why this is so important.

Answer 3

Integrins help keep the T-cell in contact with an APC, the affinity of this reaction is increased by cytokines produced when the TCR recognizes its cognate antigen. This is important because a T-cell must stay in contact with an APC for 6-12 hours to be activated.

Question 4

name two different receptors on t-cells for costimulators expressed on APCs

Answer 4

CD28 (for B7) and CD40L (For CD40)

Question 5

Give an example of an integrin binding pair between a T-cell and an APC

Answer 5

T-cell- LFA1

APC- ICAM1

Question 6

What are the 2 signals that a T-cell must receive to be activated?

Answer 6

MHC peptide - makes sure reaction is antigen specific

Costimulatory B7- expressed by APCs only when a harmful microbe is present.

Question 7

Describe the difference between B7-1 and B7-2

Answer 7

B7-2 is constitutively expressed at low levels on unstimulated DCs and blood monocytes and is responsible for the initial interaction with CD28 on T-cells. B7-1 comes up later and is what sustains the interaction with T-cells if the expressed peptide is from a pathogenic source and dangerous to the host.

Question 8

Is CD28 mediated costimulation required for effector and memory T-cells?

Answer 8

No, only for initial interaction with naive t-cells

Question 9

What are the 3 types of effector T-cells?

Answer 9

Cytotoxic T Cells, Th1 Helper T-cells, Th2 Helper T-cells

Question 10

What is the basic job of a Killer T-cell (CD8+)

Answer 10

To induce apoptosis in infected cells

Question 11

What is the job of a Th1 helper T-cell?

Answer 11

Activates macrophages, induces B-cells to produce opsonizing antibody

Question 12

What is the job of a Th2 helper T-cell?

Answer 12

Activates B-cells to make neutralizing antibody and has various effects on macrophages.

Question 13

What does IL-2 do?

Answer 13

It is a T-cell growth factor (it may also have effects on B-cells and macrophages)

Question 14

When does a helper T-cell determine if it is Th1 or Th2?

Answer 14

After it recognizes its cognate antigen and replicates. Which destiny depends on the environment.

Question 15

What signals are required for a T-cell to activate a macrophage or B-cell?

Answer 15

MHC peptide and The T cell must present CD40L to bind to the CD40 receptor on both b-cells and macrophages. Once this happens specific cytokines are used to stimulate the cell to do various things

Question 16

List the cytokines that a Th1 helper T-cell releases and what the effects are

Answer 16

IFN-gamma and CD40L - activates macrophage to destroy engulfed bacteria
Fas Ligand of TNF beta - kills chronically infected cells releasing bacteria to be destroyed by fresh macrophages
IL2 - T-cell proliferation
IL3 and GM-CSF induced production of more macrophages in bone marrow
TNF alpha and beta activates endothelium to allow macrophages into infected site
CCL2- macrophage chemotaxis

Question 17

How would CD8 primary cells need help from CD4 cells?

Answer 17

CD4 cells are much better producers of IL2 and the CD8 may need this to proliferate to an effective level

Question 18

What cytotoxic effector molecules do CD8 Tcells express?

Answer 18

Perforin, granzymes, granulysin, Fas Ligand, IFN gamma, TNF alpha and Beta

Question 19

What is the fast killing route that CD8 T-cells use?

Answer 19

granzymes and perforin (induce apoptosis, rearranges excretory pathway to target specific direction of cell

Question 20

What are the slower routes that CD8 T-cells use?

Answer 20

Membrane TNF, fas ligand, IFN gamma

Question 21

How does a CTL avoid being killed by its own mechanisms?

Answer 21

It has Cathepsin B which coats its vesicles and it has protease inhibitors that prevent granzyme B from inducing apoptosis

Question 22

How is a T-cell response terminated?

Answer 22

CTLA 4 (which is not expressed in naive T-cells) begins to be expressed after activation. Eventually it outcompetes CD28 for B7 and sends down-regulating signals to the cell

Question 23

What are some other factors besides CTLA 4 that play a role in shutting down the immune response?

Answer 23

Elimination of antigen
Elimination of other stimuli
IL-2/IL-2R signaling (via T regulatory Cells)
Killing by immunoregulatory cells

Question 24

How does T-cell become anergic?

Answer 24

If it encounters it cognate andtigen MHC but does not receive costimulation.

Question 25

What are the B-cell activating effector molecules that TH2 T-cells produce?

Answer 25

IL4, IL5, CD40L