Lecture 6A - Adaptive Immune Response to INTRAcellular Pathogens (Stiner) Flashcards
What type of cell produces IL-12?
macrophages.
what does IL-12 do?
one of its important functions is to tell NK cells to produce IFN-gamma (which activates macrophages)
NK cells have 2 types of receptors.
- Activating receptor
- binds to an NK cell ligand on a normal cell
- Inhibitory receptor
- binds to MHC I-self-peptide complex
How is an NK cell activated?
The ABSENCE of the inhibitor signal from the MHC I
-viruses can inhibit MHC I expression
What happens when an NK cell becomes activated?
degranulation of NK cell kills the infected cell.
Which cytokine helps switch a normal T cell into a Th1 cell?
IL-12
APCs secrete IL-12 in lymph nodes to switch T cells into…
Th1 cells
Where to APCs and T cells come into contact?
lymph nodes
What are the two steps of T cell activation?
- T cell receptor (TCR) binds w/ MHC on APC
- Costimulatory binding
- CD28 (on T cell) binds w/ B7 (on APC)
What does CD28 bind to?
B7
Where is CD28 located?
on T cell
Where is B7 located?
on APC
What two steps are involved when an T cell is activating a B cell?
- TCR binds w/ MHC on B cell
- Costimulatory binding
- CD40L (on T cell) binds w/ CD40 (on B cell)
Where is CD40L?
on a T cell that is working to activate a B cell
Where is CD40?
On a B cell (or a macrophage) that is being activated by a T cell
What are CD40 and CD40L involved in?
Activation of a B cell by a T cell
What do TNF-alpha and IL-1 do?
These cytokines activate endothelial cell sot express adhesion molecules.
_______ kill and ______ protect
macrophages; T cells
________ cells activate macrophages.
T cells activate macrophages by releasing IFN-gamma
Th1 immunity is induced by _______ infections.
viral (intracellular)
Th2 immunity is induced by ________ infections.
bacterial (extracellular)
What MHC does a CTL TCR recognize?
MHC 1
What are 2 accessory molecules on a CTL?
CD8
LFA-1
Where is LFA-1?
CTL
How does a CTL kill a target cell?
cytolytic GRANULOCYTES ENTER TARGET CELL and induce apoptosis
What 2 things does a CTL use to lyse a target cell?
Lytic Granules (Granzymes) Fas-FasL
Name 3 proteins inside a CTL granule and their functions
- Perforin = makes PORE
- Granzymes = PROTEASES
- Granulysin = APOPTOSIS
Do NK cells and CTL cells use the same mechanism for lysis of target cells?
yes
What induces apoptosis?
Granzyme B
What does Granzyme B do?
Induces apoptosis by activating caspases
What does granzyme B activate?
- Caspase 3, which then activates CAD.
- (or granzyme B activates CAD directly)
- Caspase 9, which also activates CAD
What does caspase 3 activate?
Caspase Activated DNAse (CAD)
What activates CAD?
Caspase 3, which was activated by granzyme B
What is Fas-FasL?
This is one of two mechanisms that CTLs use to kill target cells. The other mechanism is lytic GRANULES.
Where is Fas? Where is FasL?
Fas is on the target cell.
FasL is on the CTL
What happens when Fas (on the target cell) and FasL (on the CTL) interact?
Fas Associated Death Domain (FADD) leads to signaling domains that activate caspase 8 and 9, which activates CAD, which leads to DNA fragmentation.
Which caspases are involved in lytic granules of CTLs and target cell death?
Caspase 3 and 9
Which caspases are involved in Fas-FasL interaction between target cells and CTLs?
Caspase 8 and 9
Which T cells produce IFN-gamma to activate macrophages?
CD4+ T cells
How do pathogens fight back? (4)
- inhibit cell proteosomes (can’t present antigen)
- remove MHC 1 from ER (where it is produced)
- Block MHC synthesis
- Produce “decoy” molecules that bind to MCH 1 and prevent CD8+ cell from recognizing the cell as infected
