Diebel- Cell mediated cytotoxicity Flashcards
What does cell mediated immunity do?
Recognizes pathogen infected cells/cells w/ genetic alterations and kills them
What are antigen non-specific effector cells?
NK cells:
Macrophages
Neutrophils
Eosinophils
What are antigen specific effector cells?
CD8 T cells
CD4 T cells
What are three ways to induce the cytotoxic response?
- Non-self recognition: CTL recognizes MCHI bound to non-self antigen
- Missing self recognition: NK binds to cell w/ activated ligand but lacks MCH I
- Recognition of stress induced ligands: NK receptor binds activating ligand and stress induced ligand
What are the two mechanisms CTLs and NK cells use to kill? How is this different from NK T cells?
Cytotoxic granules and FASL-FAS interactions
NK T cells use FASL interactions predominately but can also activate NK cells INDIRECTLY
What is a CTL-P? When does it mature?
Naive T cell
Matures after interaction w/ Th CD4 T cell
What are the three sequential signals necessary for CTL-P maturation?
- antigen specific signal- TCR recognizing MCH II
- costimulatory signal- CD28:B7
- Th1–> secretes IL-2–> proliferation and differentiation of CTL-P to CTL
What are the two ways to license a DC?
- Engagement w/ activated CD40L and Helper T
2. Indirect interaction w/ pathogen–TLR molecule
What control mechanism is used to prevent self recognition by CTLs?
An antigen is only presented to CTL-P through MCH I AFTER:
- APC has “found” an pathogen through a TLR
- A CD4 has “told” it that it has found a pathogen
Which type of DC licensing (CD4 or TLR) is better for optimal proliferation/memory generation?
CD4 T cell
What does a naive CTL-P express and what does it NOT?
CD45RA–(differentiates naive from mature)
Low levels of CD2 and LFA-1
NO IL-2 or IL-2R
NO cytotoxic activity
What type of IL-2R does a mature CTL express?
HIGH affinity IL-2 R that requires high levels of IL-2 to proliferate
What are other characteristics of CTLs in regards to IL-2, adhesion molecules, cytotoxicity, etc.?
Synthesizes LOW levels of IL-2
Expresses CD45RO
HIGH levels of CD2 and LFA-21
Exhibits cytotoxicity
What IL is required to reactivate a memory CTL?
LOW levels of IL-2 for memory cells to become mature effector cells
How do mature CTLs bind target cells?
- TCR recognizes MCH I on target cell
- LFA I on CTL binds ICAM on target cell
- Antigen activation converts LFA 1 from low to high affinity state for better binding
- After 5-10 mins LFA-1 returns to low affinity state–> dissociation of CTL from target cell
What are the molecules used for CTL killing?
perforin, granzyme, fas, TNF
MOA: perforin
Forms pore >
granzyme molecules go through
MOA: granzyme
pass through pore formed by perforin>
activate apoptosis by cleavage of caspaces
MOA: Fas L
Membrane bound Fas L binds to Fas on membrane of target cell and initiates killing
Activates apoptosis by cleavage of caspaces