Lecture 23: Effector Mechanisms in Cell-mediated (T cell) Responses

Question 1

Describe the immune response to a viral infection.

Answer 1

1. virus infects and replicates within the epithelium
2. DC activation
3. T and B cell priming in the lymph node
4. adaptive immunity

Question 2

What happens if a patient lacks RAG genes?

Answer 2

there will be a lack of pathogen control

Question 3

How do DCs initiate T cell responses?

Answer 3

antigen presentation -> T cell priming

T cell priming = activation -> clonal expansion and differentiation

Question 4

What are the specific instructions DCs provide to T cells?

Answer 4

TCR activation, co-stimulation and cytokines

Question 5

What is the role of cytokines secreted by DCs onto T cells?

Answer 5

migration imprinting and functional polarisation (T cell responses are tailored to distinct pathogens)

Question 6

What happens when a skin-resident dendritic cell engages with a T cell and vitamin D is present?

Answer 6

results in upregulation of particular ligands which equips the T cell in the lymph node to home back to the skin

Question 7

What happens when a skin-resident dendritic cell engages with a T cell and retinoic acid is present (converted to retinoic acid from vitamin A)?

Answer 7

upregulates integrins such as a4b7 and certain chemokine receptors such as CCR9 on the T cell

Question 8

What is homing potential programmed by?

Answer 8

tissue-specific cues
TCR stimulation strength
inflammation in SLOs and peripheral tissues

Question 9

What do cytotoxic T cells target?

Answer 9

viruses

Question 10

What do Th1, Th17 and Th2 cells target?

Answer 10

Th1: intracellular bacteria and viruses
Th17: extracellular bacteria and fungi
Th2: parasites

Question 11

How do CD8+ T cells kill infected cells?

Answer 11

cytokines release, granule release and FasL / Fas interactions (death receptors)

Question 12

What is the process of CD8+ T cell cytotoxicity?

Answer 12

non-specific adhesion -> specific recognition and cytoskeletal changes -> granule release

Question 13

What is the role of perforin?

Answer 13

forms pores in target cell membrane and aids delivery of granzymes into target cell cytoplasm

Question 14

What are granzymes?

Answer 14

family of serine proteases

Question 15

What is the role of granzymes?

Answer 15

initiates apoptotic cell death in target cells

Question 16

What is the role of granulsyin?

Answer 16

antimicrobial actions

initiates apoptotic cell death in target cells

Question 17

What is the role of serglycin?

Answer 17

scaffold

forms complex with perforin and granzymes

Question 18

What are characteristics of apoptotic cell death?

Answer 18

immunologically silent, no inflammation, pathogen containment

Question 19

What are cytotoxic CD8+ T cells associated with?

Answer 19

IFNy production

Question 20

Which cytokines are secreted by Tc1 CD8+ T cells?

Answer 20

IFNy and TNFa

Question 21

What do “exhausted” CD8 T cells exhibit?

Answer 21

reduced functionality (reduced secretion of cytokines)

Question 22

What does persistent antigen exposure and chronic TCR stimulation lead to?

Answer 22

T cell dysfunction

Question 23

What is T-bet?

Answer 23

the major regulator that is upregulated in either a Tc1 or Th1 and is linked to the production of IFNy

Question 24

What are the effector functions of Th1 cells?

Answer 24

macrophage activation, killing, proliferation, hematopoiesis, endothelial activation and chemotaxis

Question 25

What is the role of RORyt?

Answer 25

regulates the development of Th17 cells

Question 26

What are the effector functions of Th17 cells?

Answer 26

epithelial protection, epithelial turnover, neutrophil production and chemotaxis

Question 27

What is the role of GATA-3?

Answer 27

regulates the development of Th2 cells