T-Cell Activation and Effector Function Flashcards
Activation of Naive T-Cells (General Process)
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
Which cells are the professional antigen presenting cells (APCs)?
Which APC delivers the best co-stimulation for activating naive T-Cells?
- Dendritic Cells
- Macrophages
- B-Cells
Dendritic Cells offer the best co-stimulation for activating naive T-Cells
What are the 5 different subsets of CD4+ T-Cells?
- T helper 1 (Th1)
- T helper 2 (Th2)
- T helper 17 (Th17)
- T follicular helper (Tfh)
- T regulatory cells (CD25+Foxp3+ or Treg)
Th1 Differentiation
- Response To: Intracellular Microbes
- Chemokine Activators: IL-12 and INF-y
Th2 Differentiation
Response To: Parasites/Helminths
Chemokine Activators: IL-4
Th17 Differentiation
Response To: Extracellular Fungi/Bacteria
Chemokine Activators: IL-1, IL-6, IL-23, and TGF-B
Where do T-cellls differentiated into CD4+ or CD8+ T-cells?
In the Thymus
Where do Helper T-Cells get actived into the different types of Helper T-Cells (Th1, Th2, Th17, Treg)
In the Lymph Node
Th1 Role
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
Th2 Role
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
Th17 Role
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
IL-2
Action: T-Cell proliferation; regulatory T-Cell survival
Source: Activated T-Cells
IFN-y
Action: Activate Macrophages (classical pathway)
Source: Th1, Cytotoxic T-Cells, NK Cells
IL-4
Action:
- Causes B-Cells to make IgE
- Macrophage activation (alternative pathway/tissue repair)
Source: Th2 and Mast Cells
IL-5
Action: Activates Eosinophils
Source: Th2 and Mast Cells
IL-13
Action:
- Causes B-Cells to make IgE
- Macrophage activation (alternative pathway/tissue repair)
Source: Th2 and Mast Cells
IL-17
Action: Stimulates acute inflammation
Source: Th17
IL-21
Action:
- B-Cell Activation
- Tfh differentiation
Source: Tfh
IL-22
Action: Maintenance of epithelial barrier function
Source: Th17 and NK Cells
CD8+ T-Cell (Cytotoxic T-Cell) Activation
- 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
How do activated Cytotoxic T-Lymphocytes kill their targets?
- TCR binds specific MHC I/Peptide complex
- This activates granule exocytosis
- These granules signal to the infected cell to undergo apoptosis
How do CD4+ and CD8+ T-Cells cooperate to destroy intracellular microbes?
- Th1 activates macrophages to kill ingested microbes
- Cytotoxic T-Cells cause virally infected cells to undergo apoptosis
T follicular helper (Tfh) role
Releases:
- IL-21: Leads to B-Cell and Tfh differentiation
What can occur if Th2 cells become unregulated?
- Allergies
