Lecture 17: T Cells I

Question 1

What are some of the different roles of the different effector T cells?

Answer 1

1) Some help active B cells.
2) Some help activate macrophages.
3) Some kill infected cells directly.

Question 2

How do T cells travel to the site of infection?

Answer 2

• efferent lymphatic vessels -> thoracic duct -> blood stream.

Question 3

What is Signal 3 in T-cell activation, and what is its role?

Answer 3

1) Signal 3 = Cytokines directing T-cell differentiation into distinct effector cell types.

2) All 3 signals trigger intracellular signaling leading to:
- Activation
- Proliferation
- Survival
- Differentiation

Question 4

What are the two key outcomes of lymphocyte activation?

Answer 4

(1) Proliferation (in response to IL-2)
(2) Differentiation into distinct T cell types

Question 5

What do activated T cells differentiate into?

Answer 5

• CD4+ T helper cells differentiate from TH0 into:
  TH1
  TH2
  TFH (T follicular helper)
  TH17
  Other subtypes
• CD8+ T cells differentiate into:
  Cytotoxic T lymphocytes (CTL)
• Some T cells differentiate into:
  Regulatory T cells (Tregs)

Question 6

What are effector T cells, and where do they come from?

Answer 6

Effector T cells are differentiated T cells that arise from activated T cells. They:
-> Are classified based on transcription factors, cytokine profile, and function
-> Do not require co-stimulation once activated
-> Their fate is determined by cytokines

Question 7

What do naïve CD8+ T cells differentiate into?

Answer 7

They differentiate into cytotoxic T lymphocytes (CTLs), which kill infected or cancerous cells.

Question 8

What are the 5 main effector T cell subtypes?

Answer 8

1) TH1
2) TH2
3) TH17
4) TFH (T follicular helper)
5) Treg (Regulatory T cells)

Question 9

How do effector T cells influence adaptive immunity?

Answer 9

• Different cytokines = different functions
• They impact other immune cells
• They help clear different microorganisms

Question 10

How do APCs trigger the release of polarizing cytokines?

Answer 10

(1) APCs bind PAMPs using PRRs.
(2) This triggers cytokine secretion.
(3) Different PAMPs engage different PRRs, leading to different cytokines produced.

Question 11

What are polarizing cytokines, and what do they do?

Answer 11

Polarizing cytokines = Signal 3 cytokines that guide T helper cells into specific effector subsets (e.g., TH1, TH2, etc.).

Question 12

Give an example of how pathogens influence polarizing cytokines and T helper differentiation.

Answer 12

• Viruses → stimulate IL-12 → induces TH1 subset
• Worms/helminths → stimulate IL-4 → induces TH2 subset

Question 13

How does Signal 3 (polarizing cytokines) influence T cell differentiation?

Answer 13

• Cytokines bind cytokine receptors
• This triggers signaling through STAT proteins
• Phosphorylated STAT proteins act as transcription factors
• STAT proteins drive expression of a Master Transcriptional Regulator
• This Master TF binds promoter regions for genes encoding specific effector cytokines
• This determines the fate and function of the differentiated T cell subtype

Question 14

What is the role of STAT proteins in T cell differentiation?

Answer 14

• STAT proteins are activated by cytokine signaling
• Phosphorylated STATs act as transcription factors
• They promote expression of a Master Transcriptional Regulator, which defines the effector T cell subtype.

Question 15

What is the Master Transcriptional Regulator and why is it important in T cell differentiation?

Answer 15

• It is a key transcription factor produced in response to Signal 3 cytokines.
• It binds promoter regions of genes for effector cytokines.
• This controls which effector T cell subtype develops and what functions it will perform.