BIOL 435 Ch. 12 p.2 (Effector Responses)

Question 1

3 subsets of cytotoxic effector cells

Answer 1

1. CTLs
2. NK T cells
3. NK cells

Question 2

cytotoxic effector cells

Answer 2

• can eliminate infected cells and abnormal tumor cells
• each has slightly different killing mechanism triggers
• each induces apoptosis in targets

Question 3

effector CTL generation

Answer 3

• 3 signals

- APCs get help from T cells to up regulate stimulation molecules

Question 4

signal 1 (CTL)

Answer 4

-TCR binds peptide presented by APC on MHC Class I

Question 5

signal 2 (CTL)

Answer 5

-costimulatory signal transmitted by CD28-B7 interaction between T cell and APC

Question 6

signal 3 (CTL)

Answer 6

-provided by IL-2

>induces proliferation and differentiation into CTL-form

Question 7

CTL response

Answer 7

-recognize and kill infected or tumor cells via T cell receptor activation

Question 8

best CTL activation acheived when

Answer 8

-APC used can present peptides on both types of MHC molecules
>not all cells can do that though
*cross presentation

Question 9

cross presentation

Answer 9

-allows DC to acquire Ag from non-APCs and present them on both types of MHC molecules
>solves the problem
>provides best stimulation for CTL activation

Question 10

Tc1

Answer 10

• secrete IFN-gamma but not IL-4

- can use perforin and Fas-mediated death induction

Question 11

Tc2

Answer 11

• differentiate in presence of IL-4
• secrete IL-4 and IL-5
• appear to only use perforin death-induction strategies

Question 12

2 mechanisms of CTLs

Answer 12

1. Directional release of granule contents
   >perforin/granzyme pathways
2. Fas/FasL pathways
   *both induce apoptosis in target cell
   *require immediate contact: “kiss of death”

Question 13

directional release

Answer 13

1. Granules developed once activated
2. Cytoplasmic rearrangement
   >Golgi repositiions to “aim” at target
3. Granule exocytosis

Question 14

granzyme/perforin mediated cytolysis

Answer 14

-when stimulated, CTLs release granule contents
*both taken up by endocytoic process
>then punch holes in membranes and induce apoptosis from the inside

Question 15

perforin

Answer 15

-pore forming protein

Question 16

granzyme

Answer 16

-sereine proteases

Question 17

Fas-FasL mediated cytolysis

Answer 17

-Fas bound by FasL initiates a death signal leading to apoptosis

Question 18

NK cells functions

Answer 18

• recognize and kill infected cells and tumor cells by their absence of MHC Class I
• help regulate innate/adaptive immunity by cytokine secretion

Question 19

NK cells properties

Answer 19

• make up 5-10% of circulating lymphocytes
• lack specific Ag receptors
• proliferate earlier in infection than CTLs

Question 20

phenotype of NK cells

Answer 20

-lymphoid cells derived from CLPs in bone marrow
>thymus not required for NK development
-do not undergo receptor gene rearrangements

Question 21

defining trait of NK cells

Answer 21

-expression of a set of activating and inhibiting NK receptors
>these receptors determine whether to kill a target or not

Question 22

normal cells present a

Answer 22

1. Ligand for activating (killing) receptor on NK cells
2. An MHC class I ligand for the inhibitory receptor
   * tolerance

Question 23

missing self model

Answer 23

• when viruses infect cells, some may inhibit MHC class I expression to evade detection and elimination by CTLs
• loss of MHC molecule expression promotes killing of altered self cell

Question 24

balanced signals model

Answer 24

• balance of inhibitory vs activating signals determines whether NK is activated or not
• up regulation of stress-induced ligands promotes killing of altered self-cell

Question 25

how NK cells induce apoptosis?

Answer 25

-once activating signal molecules are engaged, NK cells use mechanisms very similar to CTLs to induce target cell death

Question 26

NK ‘licensing’ and regulation

Answer 26

-NK cell don’t automatically posses killing potential
-“licensed” to kill by a prior interaction with a healthy cell through MHC class I/inhibitory receptor interactions
>gives “license”

Question 27

gives “license”

Answer 27

-only to those NK cells that can exhibit restraint when encountering a healthy, normal cell

Question 28

NK cell memory

Answer 28

• some evidence suggest they can

- very new idea

Question 29

NKT cells

Answer 29

-bridge innate/adaptive immune systems
-can act as helper cells or killer cells
>killing seems dependent on Fas-FasL interactions
-don’t form memory cells

Question 30

NKT cell properties

Answer 30

• posses a TCR, but it is invariant
• include both CD4+ and CD4- cell types
• posses NK surface proteins rather than T-cell varieties

Question 31

TCR NKT cells

Answer 31

-recognizes glycolipids presented by nonpolymorphic CD1d (not MHC)