Lecture 16

Question 1

What two types of T-cells can have CD8?

Answer 1

Cytotoxic T-lymphocytes or CD8+ (memory) cells

Question 2

T/F: CD8 T-cells recognize their antigen from MHC II receptors.

Answer 2

False - CD8 cells recognize their antigen from MHC I receptors

Question 3

What is apoptosis?

Answer 3

Programmed cell death or cell suicide. Involves controlled dismantling of the target cell.

Question 4

What are the two major pathways of apoptosis?

Answer 4

1. Intrinsic or mitochondrial pathway
2. Extrinsic or death receptor pathway

Question 5

What is a caspase?

Answer 5

Endopeptidases that are important in maintaining homeostasis through regulating apoptosis and inflammation.

Question 6

List the initiator caspases and what their function is.

Answer 6

2,8,9,10,14; Activated by multimolecular death complexes.

Question 7

List the effector caspases and what their function is.

Answer 7

3,6,7; Break down cellular structures.

Question 8

List the inflammatory caspases and what their function is.

Answer 8

1,4,5,11; Activated my multimolecular inflammasomes.

Question 9

Describe the steps of the intrinsic pathway.

Answer 9

1. Cell stress or DNA damage occurs, releasing granzymes as well as acting on bcl-2 proteins.
2. Granzymes enter the cell through transmembrane proteins called perforins.
3. The granzymes then acto on the mitochondrion and release cytochrome C.
4. Cytochrome C then leads to apoptosome, activating Caspas-9.
5. Which then activates the effector caspases (3,6,7).
6. Leading to DNA fragmentation, cytoskeletal disruption, and chromatin disruption.
7. Apoptosis

Question 10

Describe the steps of the Extrinsic pathway.

Answer 10

1. CD95 ligand binds to the CD95 receptor, which is attached to a DISC (death inducing signaling complex)
2. Activated Caspas-8
3. Which then activates the effector caspases (3,6,7).
4. Leading to DNA fragmentation, cytoskeletal disruption, and chromatin disruption.
5. Apoptosis

Question 11

What are the morphological features of a cell going through apoptosis?

Answer 11

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

Question 12

What are the 5 stages of cytotoxic T cell responses?

Answer 12

1. Activation of naive CTL
2. Proliferation and differentiation of activated CTL into daughter cells
3. Differentiation of pre-CTL in an inflammatory site into an armed CTL
4. Activation of the armed CTL
5. CTL-mediated destruction of the target cell

Question 13

What is the difference between activation of naive T cells and armed CTL’s?

Answer 13

Armed CTL’s need engagement by only a single TCR by a single specific pMHC; whereas naive T cells also need costimulation.

Question 14

What is the interaction between the CTL and the target cell called?

Answer 14

Immunological synapse

Question 15

What interaction occurs in the inner adhesion ring of the immunological synapse?

Answer 15

CD2/CD48

Question 16

What interactions occurs in the central zones of the immunological synapse?

Answer 16

• CD95-ligand, perforins
• TCR/CD3, CD28/CD80

Question 17

Which area of the immunological synapse contains the lethal actions from the CTL?

Answer 17

Inner adhesion ring

Question 18

What are the steps in the Perforin pathway of cell killing?

Answer 18

1. Cytoskeleton of the CTL reorganizes to bring cytotoxic granules to the site of CTL-target cell contact.
2. The granules fuse with CTL membrane and their contents are directionally exocytosed towards the target cell membrane.
3. Perforin & granzymes are major contents of these granules.

Question 19

T/F: Naive cytotoxic T cells do not expresses Fas-ligand, it is only after activation and conjugate formation that FasL is expressed.

Answer 19

True

Question 20

What is the result of Fas engagement on a target cell bu FasL or CD95L?

Answer 20

Death of the target cell by apoptosis.

Question 21

List the major immune pathways of killing target cells.

Answer 21

1. CTL - perforins and granzymes - MHC restricted
2. Macrophage - cytolytic enzymes and NO - not MHC restricted
3. Neutrophil - ADCC - not MHC restricted
4. NK cell - perforins - not MHC restricted

Question 22

Which of the major immune pathways is the most efficient at killing the target cell?

Answer 22

CTL - perforins and granzymes - MHC restricted

Question 23

Describe the process of macrophage activation using a Th1 cell.

Answer 23

1. Phagocytosis of an antigen
2. Antigen processing
3. Antigen presentation
4. Co-stimulation
5. Th1 cell produces IFN-y and IL-2
6. Activated macrophage

Question 24

Describe the process of macrophage activation using a NK cell.

Answer 24

1. Phagocytosis of an antigen
2. IL-12 and TNF -a production
3. NK cell produces IFN-y
4. Activated macrophage

Question 25

Which pathway produces a fully activated macrophage?

Answer 25

Th1 pathway

Question 26

What is the classical activation process of a macrophage?

Answer 26

1. Th1 cells produce IFN-y, TNF-a, and IL-12
2. Activates a M1 macrophage
3. Increased IL-1, IL-6, IL-12, IL-23, NO, and iNOS
4. Increased antimicrobial activities

Question 27

What is the alternative activation of a macrophage?

Answer 27

1. Th2 cells and Treg cells secrete IL-4, IL-10, and IL-13.
2. Activates a M2 macrophage
3. Increased IL-1RA, IL10, Arginase, and TGF-B
4. Stimulates wound healing and immune regulation