T-Cell Activation and Effector Function

Question 1

Activation of Naive T-Cells (General Process)

Answer 1

Antigen Presenting Cell (APC) delivers 3 signals to activate T-cell:

• TCR binds appropriate MHC/peptide complex
• B7 (AKA CD80 or CD86) on APC binds CD28 on T-Cell
• APC releases different cytokines which determine specific differentiation

Question 2

Which cells are the professional antigen presenting cells (APCs)?

Which APC delivers the best co-stimulation for activating naive T-Cells?

Answer 2

• Dendritic Cells
• Macrophages
• B-Cells

Dendritic Cells offer the best co-stimulation for activating naive T-Cells

Question 3

What are the 5 different subsets of CD4+ T-Cells?

Answer 3

• T helper 1 (Th1)
• T helper 2 (Th2)
• T helper 17 (Th17)
• T follicular helper (Tfh)
• T regulatory cells (CD25+Foxp3+ or Treg)

Question 4

Th1 Differentiation

Answer 4

• Response To: Intracellular Microbes
• Chemokine Activators: IL-12 and INF-y

Question 5

Th2 Differentiation

Answer 5

Response To: Parasites/Helminths

Chemokine Activators: IL-4

Question 6

Th17 Differentiation

Answer 6

Response To: Extracellular Fungi/Bacteria

Chemokine Activators: IL-1, IL-6, IL-23, and TGF-B

Question 7

Where do T-cellls differentiated into CD4+ or CD8+ T-cells?

Answer 7

In the Thymus

Question 8

Where do Helper T-Cells get actived into the different types of Helper T-Cells (Th1, Th2, Th17, Treg)

Answer 8

In the Lymph Node

Question 9

Th1 Role

Answer 9

Releases:

• IFN-y: Activates Macrophages to kill intracellular microbes
• IL-2: Activates Cytotoxic T-Cells and clonal expansion of CD4+ and CD8+ T-Cells

Activation of Macrophages to kill intracellulsar microbes:

• TCR binds specific MHC II/Peptide on Macrophage
• CD40L on Th1 binds CD40 on Macrophage
• IFN-y released by Th1 binds to receptor on Macrophage

Question 10

Th2 Role

Answer 10

Releases:

• IL-4: Activates B-cells to produce IgE antibodies
  
  • IgE Ab coats parasites
  • IgE also leads to Mast Cell Degranulation
• IL-5: Activates Eosinophils which bind Ab coated parasite and release enzymes that destroy the parasite
• IL-4 and IL-13:
  
  • Alternative macrophage activation (enhanced fibrosis/tissue repair)
  • Intestinal mucus secretion and peristalsis

Question 11

Th17 Role

Answer 11

Releases:

• IL-17: Inflammation and Neutrophil Recruitment/Activation
• IL-22: Increased Epithelial barrier integrity

IL-17 and IL-22 both cause Epithelial cells to release Anti-Microbial Peptides

Question 12

IL-2

Answer 12

Action: T-Cell proliferation; regulatory T-Cell survival

Source: Activated T-Cells

Question 13

IFN-y

Answer 13

Action: Activate Macrophages (classical pathway)

Source: Th1, Cytotoxic T-Cells, NK Cells

Question 14

IL-4

Answer 14

Action:

• Causes B-Cells to make IgE
• Macrophage activation (alternative pathway/tissue repair)

Source: Th2 and Mast Cells

Question 15

IL-5

Answer 15

Action: Activates Eosinophils

Source: Th2 and Mast Cells

Question 16

IL-13

Answer 16

Action:

• Causes B-Cells to make IgE
• Macrophage activation (alternative pathway/tissue repair)

Source: Th2 and Mast Cells

Question 17

IL-17

Answer 17

Action: Stimulates acute inflammation

Source: Th17

Question 18

IL-21

Answer 18

Action:

• B-Cell Activation
• Tfh differentiation

Source: Tfh

Question 19

IL-22

Answer 19

Action: Maintenance of epithelial barrier function

Source: Th17 and NK Cells

Question 20

CD8+ T-Cell (Cytotoxic T-Cell) Activation

Answer 20

• MHC I on APC binds specific TCR
• B7 on APC binds CD28 on T-Cell

A very good interaction of the above leads to activation; helper T-cells can assist with this process:

• Helper T-Cells produce cytokines (e.g. IL-2) that promotes CTL differentiation
• Helper T-Cells also enhance the ability of APCs to stimulate CTL differentiation

This licenses the CTL (Cytotoxic T-Lymphocyte) to kill

Question 21

How do activated Cytotoxic T-Lymphocytes kill their targets?

Answer 21

• TCR binds specific MHC I/Peptide complex
• This activates granule exocytosis
• These granules signal to the infected cell to undergo apoptosis

Question 22

How do CD4+ and CD8+ T-Cells cooperate to destroy intracellular microbes?

Answer 22

• Th1 activates macrophages to kill ingested microbes
• Cytotoxic T-Cells cause virally infected cells to undergo apoptosis

Question 23

T follicular helper (Tfh) role

Answer 23

Releases:

• IL-21: Leads to B-Cell and Tfh differentiation

Question 24

What can occur if Th2 cells become unregulated?

Answer 24

• Allergies

Question 25

What can occur if Th1 cells become unregulated?

Answer 25

• Autoimmunity
• Chronic inflammation

Question 26

What can occur if Th17 cells become unregulated?

Answer 26

• Autoimmunity

Question 27

Foxp3+ T regulatory cells (Treg) differentiation

Answer 27

TGF-B and IL-2 help CD4+ cells differentiate into Treg cells

Question 28

Treg role

Answer 28

• Suppress over-active T-Cell response
• Limit innate/inflammatory response
• Prevent autoimmunity

Releases:

• IL-10: Supresses macrophage function
• TGF-B: Induces generation of more Treg cells

Question 29

Memory CD4+ and CD8+ (General Concept)

Answer 29

• Can undergo rapid recall expansion in re-infection
• Immune memory is the principle for vaccine development