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
MOA:TNF
CTLS kill by TNF production and secretion
What are the two main pathways to apoptosis?
- Serine proteases (granzymes) cleave Bid and procaspace 3–> apoptosis
- FasL binds Fas and activates death domains that cleave caspace 8–> apoptosis
What do NK cells do?
Kill virus infected cells
intracellular pathogen infected cells
tumor cells
EARLY defense against virus
NK cells are induced by….
IFN, alpha, beta, gamma
TNF alpha
IL 15
NK cells produce…
IFN-y