Assignment #9-w/o review objectives

Question 1

CD8+ cytotoxic T lymphocytes emerge from the the thymus as what precursor cells?

Answer 1

pCTL

Question 2

what tissue does the differentiation of pCTL to CTL happen in?

Answer 2

secondary lymphoid tissues (endocytosis, processing and presentation happen en route to this tissue)

Question 3

what antigen presenting cells are involved in differentiation of pCTL to CTL?

Answer 3

dendritic cells present peptide-MHC class II to CD4+ Thp that secrete IL-2

Question 4

what cytokine is involved in clonal expansion of pCTL to CTL?

Answer 4

IL-2 binding to IL-2R (CD25) and IFNgamma

Question 5

what is the role of IL-2 in pCTL to CTL differentiation?

Answer 5

IL-2:IL-2(R) interaction leads to proliferation of the activated pCTL

Question 6

what is the number of days required for maturation from pCTL to CTL?

Answer 6

7-10 days and again IL-2 and IFNgamma are required

Question 7

Interaction of IL-2 to IL-2R (CD25) leads to clonal expansion. what is clonal expansion?

Answer 7

clonal expansion = proliferation

and proliferation again leads to activation of the pCTL

Question 8

Conjugate formation between the target cell and the pCTL is stabilized by high avidity interaction of what adhesion molecules?

Answer 8

CD2 with LFA-3 and LFA-1 with ICAM (1-2)

Question 9

Dendritic cell presents antigenic peptide-MHC to CD4+ Thp cells and to CD8+ pCTL. what are the steps leading up to presentation of Thp cells? Each card will go through a step. Step 1

Answer 9

1) endocytosis of exogenous antigen into the endosome

Question 10

step 2 in presentation to Thp?

Answer 10

2) lysosomes fuse with endosome; enzymes degrade antigen

Question 11

step 3 in presentiation to Thp?

Answer 11

3) Endosome-lysosome vesicle fuse with vesicle transporting class II/MHC/invariant chain in vesicle; Lysosomal enzymes degrade invariant chain

Question 12

step 4 in presentation to Thp?

Answer 12

4) peptides bind to groove in MHC class II; vesicles migrate to cell surface

Question 13

step 5 in presentation to Thp?

Answer 13

5) vesicles fuse with outer membrane

Question 14

step 6 in presentation to Thp?

Answer 14

6) peptide-MHC class II complex expressed on cell surface

Question 15

Dendritic cell presents antigenic peptide-MHC to CD8+ pCTL as well. what are the steps to pCTL presentation? Again each card with go through a step. step one

Answer 15

1) endocytosis of exogenous antigen into the endosome

Question 16

step 2 in presentation to pCTL?

Answer 16

2) cross presentation of exogenous antigen (unknown mechanism)

Question 17

step 3 in presentation to pCTL?

Answer 17

3)binding of peptide to MHC class I in a vacuole and transport to the cell surface.

Question 18

step 4 in presentation to pCTL?

Answer 18

4) Peptide-MHC class I complex expressed on cell surface

Question 19

step 5 in presentation to pCTL?

Answer 19

5) presentation to pCTL= cross priming

Question 20

what are target cells?

Answer 20

are cells that have antigenic peptide-MHC class 1 molecules on their cell surface

Question 21

what are the steps in antigen processing and presentation by a target cells in the periphery? each card will go through one step. step one

Answer 21

1) Antigen must be present in target cell cytosol. Antigen is then destroyed by proteasome, fragments presented to TAP-1 and TAP-2, bind MHC class I in ER, golgi vesicle transports complex to cell membrane.

Question 22

step two in target cell?

Answer 22

2) the MHC class I peptide is now expressed on target cell surface and is recognized by circulating CTLs

Question 23

step three in target cell?

Answer 23

3) interaction of the CTL with target cell leads to destruction of target cell (termed lethal hit)

Question 24

what armamentarium present in the granules extruded by the CTL?

Answer 24

the polarized release of lytic granules containing perforin and granzymes ensures specificity of killing (killing of target cells but not the CTL itself)

Question 25

once the CTL molecule delivers this lethal hit, what happens to it?

Answer 25

CTL is unimpaired by the lytic process and once it has delivered this lethal hit, it detaches and continues its function of immunological surveillance

Question 26

This lethal hit leads to release of granules containing perforin and granzymes. Perforin is a pore forming protein that inserts into the target cell membrane. There are two models in regards to the mechanism behind death of the target cell. what is the first model?

Answer 26

1) the pores allow entry of granzymes that trigger activation of caspases and apoptosis of the cells

Question 27

second model?

Answer 27

2) this model, which is calcium dependent, insertion of perforin leads to colloidal swelling and osmotic lysis.

Question 28

After elimination of virally infection cells, the antigenic stimulus for expansion of the specific CD8+ T cell pool disappears. What happens to the T cells now?

Answer 28

1) many activated T cells will die
2) others will become dormant and are referred to as memory cells. (now if patient is reinfected the infection can be destroyed much sooner)

Question 29

Memory CD8+ T cells can occur anywhere that the T cell encounters a cell expressing what?

Answer 29

the same class I MHC peptide that triggered its activation

Question 30

For the most part viruses are sequestered within cells; however during infectivity or release from cells it is vulnerable to attack by the immune system. What components of the immune system are activated when the virus is outside the cell?

Answer 30

when viruses are extracellular they are targets for immune processes that include phagocytes, antigen presenting cells, B cells and antibodies.

Question 31

Viral infection initiates processes that lead to secretion of IFNgamma. Neighboring cells bind IFNgamma via constitutively expressed receptors. what are the steps in the mechanism that lead to this receptor ligand interaction that facilitates control of the viral infection. Each card will go through a step

Answer 31

1) IFNgamma binds to cognate receptors on neighboring cells-signaling leads to the production of 2,5-oligoadenylate synthase (2,5-OAS)

Question 32

step 2 in IFNgamma?

Answer 32

(2,5-OAS) leads to activation of RNase L, which degrades viral and cellular RNA

Question 33

step 3 in IFNgamma?

Answer 33

3) Once inside the cell host defenses take action NK cells (innate) and Cytotoxic T cells (adaptive)

Question 34

If a dendritic cell is directly infected, what happens??

Answer 34

It will become a target cell and not a professional antigen presenting cell

Question 35

what is the impact of increased MHC class I expression on killing of virally infected cells by CTLs?

Answer 35

1) Reduces the likelihood that the infected cell will be destroyed by NK cells
2) Strengths the likelihood of destruction by CTLs

Question 36

what is the impact of increased MHC class II expression on killing of virally infected cells by CTLs?

Answer 36

1) Strengthens the likelihood that the infected cell will be destroyed by NK cells
2) Reduces the likelihood that it will be destroyed by CTLs.

Question 37

In an HIV infection gp120 on HIV binds to CD4 on what target cells?

Answer 37

CD4+ T cells, Dendritic cells, and macrophages

Question 38

What are two coreceptors on target cells in an HIV infection?

Answer 38

CXCR4 required by T tropic strains of HIV

CCR5 required by M tropic strains of HIV

Question 39

why does a decline in the CD4+ T cell numbers leads to non antigen specific immunosuppression?

Answer 39

CD4+ T cells are the main target of HIV infection, regardless of their antigenic specificity. This produces a decline in the CD4+ T cell numbers and a non antigen specific immunosuppression.