Lecture 18 - T cell function and destruction of cell associated invaders

Question 1

Two CD8 functions

Answer 1

1. cytotoxic/regulatory
2. memory

Question 2

Cytotoxic T lymphocytes are CD_

Answer 2

CD8+

Question 3

What do CD8+ T cells recognize antigens on

Answer 3

MHC I

Question 4

What happens once CD8+ T cells recognize antigen on MHCI

Answer 4

clonally expand, differentiate, and develop a killing machinery in their cytoplasm

Question 5

When do CD8+ T cells kill a cell

Answer 5

kill cells that have the antigen it recognizes bound to an MHC I molecule

Question 6

CD8+ T cells are important in

Answer 6

protection from intracellular microbes that cause the synthesis of foreign proteins in the cytoplasm such as viruses

Question 7

Apoptosis

Answer 7

programmed cell death or cell suicide that involves the controlled dismantling of intracellular components while avoiding inflammation and damage to surrounding cells

Question 8

Initiator caspases activate

Answer 8

executioner caspases that subsequently coordinate their activities to demolish key structural proteins and activate other enzymes

Question 9

What are the morphological hallmarks of apoptosis

Answer 9

DNA fragmentation and membrane blebbing

Question 10

What are the hallmarks of necrosis

Answer 10

membrane degradation, release of cytoplasmic contents, inflammation, involvement of larger area

Question 11

2 major pathways of apoptosis

Answer 11

1. intrinsic or mitochondrial
2. extrinsic or death receptor pathway

Question 12

What is the role of caspases in inflammation and apoptosis

Answer 12

endopeptidases that are important in maintaining homeostasis through regulating apoptosis and inflammation

Question 13

What do initiator caspases do

Answer 13

activated by multimolecular death complexes

Question 14

What do effector caspases do

Answer 14

break down cellular structures

Question 15

What do inflammatory caspases do

Answer 15

activated by multimolecular inflammasomes

Question 16

What are the initiator caspases

Answer 16

2, 8, 9, 10, 14

Question 17

What are the effector caspases

Answer 17

3, 6, 7

Question 18

What are the inflammatory caspases

Answer 18

1, 4, 5, 11

Question 19

How does caspase get activated intrinsically

Answer 19

cell stress, DNA damage->granzymes->release cyt c from mitochondrion->apoptosome->activate caspase 9->activate effector caspase->DNA frag, cytoskeleton disruption, chromatin disruption->apoptosis

Question 20

How does capsase get activated extriniscally

Answer 20

CD95L->DISC->caspase 8 activation->activate effector caspase->DNA frag, cytoskeleton disruption, chromatin disruption->apoptosis

Question 21

List the characterisitcs of apoptosis in order

Answer 21

1. normal cell
2. clumping of chromatin, blebbing, loss of organelles
3. nuclear fragmentation, apoptotic bodies
4. apopotic bodies

Question 22

Steps of apoptosis with cytotoxic T cell responses

Answer 22

1. antigen recognition and binding of CTL to target cell
2. CTL activation and granule exocytosis
3. apoptosis of target cell

Question 23

Cytotoxic T cell responses occur in 5 stages:
1. Activation of ______ by a DC in _____
2. ___ and ____ of the activated CTL cell into daughter cells called ____
3.____ of a pre-CTL in an inflammatory site into an “____” CTL
4. ______ of the armed CTL by encounter with specific _____ presented by _____ on a target cell
5. ______ of the target cell as well as other cells displaying the identical _____

Answer 23

1. naive CTL, secondary lymphoid tissue
2. Proliferation, differentiation, Pre-CTLs
3. armed
4. Activation, non-self peptide, MHC Class I
5. CTL-mediated destruction, pMHC

Question 24

Unlike naive T cells, to activate armed CTL, what is needed and what is NOT needed

Answer 24

only engagement of single TCR by a single specific pMHC is needed, no costimulation needed

Question 25

Perforin pathway of cell killing 1. After conjugate formation, ___ of the CTL reorganizes to bring cytotoxic ___ to the site of ____ contact. * The granules fuse with ____ and their contents are directionally ___ towards the target cell membrane. * ___ & ___ are major contents of these granules. * Perforin is a ___ and the granzymes are a family of ____

Answer 25

1. cytoskeleton, granules, CTL-target cell 2. CTL membrane, exocytosed 3. perforin, granzymes 4. pore-forming protein, serine proteases

Question 26

What is CD95 or Fas

Answer 26

transmembrane death receptor that is widely expressed on mammalian cells

Question 27

What do naive cytotoxic T cells NOT express, what do they express after activation and conjugate formation

Answer 27

Fas-ligand (FasL/CD95L); FasL on CTL surface

Question 28

Engagedment of Fas on a target cell by FasL or CD95L expressed by armed CTL results in

Answer 28

death of the target cell by apoptosis

Question 29

What does the CD95L-CD95 system regulate

Answer 29

T cell survival

Question 30

What happens to do unwanted surplus or self-reactive T cells

Answer 30

eliminated once they have served their functions

Question 31

Killing target cells using immune pathways MHC restricted or not?? 1. cytotoxic T cell 2. Macrophage 3. Neutrophil 4. NK cell

Answer 31

1. yes 2. no 3. no 4. no

Question 32

What is the most efficient pathway of killing target cells

Answer 32

cytotoxic T cell

Question 33

What are activated macrophages capable of killing

Answer 33

resistant intracellular bacteria

Question 34

How can macrophages be activated

Answer 34

1. infection 2. phagocytosis 3. TNF a 4. IL-12->Th1 cell 5. IFNy, IL-2 6. fully activated macrophage

Question 35

What can lead to an incompletely activated macrophage vs a fully activated macrophage

Answer 35

NK cell; Th1 cell

Question 36

M1 macrophages are activated by what activation

Answer 36

classical activation

Question 37

Describe classical activation

Answer 37

1. Th1 cells 2. IFNy, TNF a, IL-2 3. M1 4. increases IL-1, 6, 12, 23, NO, INOS

Question 38

M2 macrophages are activated by what activation

Answer 38

alternative activation

Question 39

Describe alternative activation

Answer 39

1. Th2 cells, Treg 2. IL-4, 10, 13 3. M2 4. Increases IL-1RA, 10, Arginase, TGF B

Question 40

Function of M1 macrophages

Answer 40

increased antimicrobial activities

Question 41

Functions of M2 macrophages

Answer 41

wound healing and immune regulation

Question 42

Cytotoxic extrinsic pathway includes ___ while the instrinsic pathway includes ____

Answer 42

1. perforins, granzymes 2. Fas, ligand

Question 43

Some bacteria and parasites may evade destruction by living within the ____ of phagocytic cells, especially macrophages. The elimination of these intracellular organisms is mediated by activation of ___ macrophages by ____ produced by ___ cells.

Answer 43

1. endosomes 2. M2 3. IFNy 4. Th1