BIOL 435 Ch. 12 p.2 (Effector Responses) Flashcards
3 subsets of cytotoxic effector cells
- CTLs
- NK T cells
- NK cells
cytotoxic effector cells
- can eliminate infected cells and abnormal tumor cells
- each has slightly different killing mechanism triggers
- each induces apoptosis in targets
effector CTL generation
- 3 signals
- APCs get help from T cells to up regulate stimulation molecules
signal 1 (CTL)
-TCR binds peptide presented by APC on MHC Class I
signal 2 (CTL)
-costimulatory signal transmitted by CD28-B7 interaction between T cell and APC
signal 3 (CTL)
-provided by IL-2
>induces proliferation and differentiation into CTL-form
CTL response
-recognize and kill infected or tumor cells via T cell receptor activation
best CTL activation acheived when
-APC used can present peptides on both types of MHC molecules
>not all cells can do that though
*cross presentation
cross presentation
-allows DC to acquire Ag from non-APCs and present them on both types of MHC molecules
>solves the problem
>provides best stimulation for CTL activation
Tc1
- secrete IFN-gamma but not IL-4
- can use perforin and Fas-mediated death induction
Tc2
- differentiate in presence of IL-4
- secrete IL-4 and IL-5
- appear to only use perforin death-induction strategies
2 mechanisms of CTLs
- Directional release of granule contents
>perforin/granzyme pathways - Fas/FasL pathways
*both induce apoptosis in target cell
*require immediate contact: “kiss of death”
directional release
- Granules developed once activated
- Cytoplasmic rearrangement
>Golgi repositiions to “aim” at target - Granule exocytosis
granzyme/perforin mediated cytolysis
-when stimulated, CTLs release granule contents
*both taken up by endocytoic process
>then punch holes in membranes and induce apoptosis from the inside
perforin
-pore forming protein
granzyme
-sereine proteases
Fas-FasL mediated cytolysis
-Fas bound by FasL initiates a death signal leading to apoptosis
NK cells functions
- recognize and kill infected cells and tumor cells by their absence of MHC Class I
- help regulate innate/adaptive immunity by cytokine secretion
NK cells properties
- make up 5-10% of circulating lymphocytes
- lack specific Ag receptors
- proliferate earlier in infection than CTLs
phenotype of NK cells
-lymphoid cells derived from CLPs in bone marrow
>thymus not required for NK development
-do not undergo receptor gene rearrangements
defining trait of NK cells
-expression of a set of activating and inhibiting NK receptors
>these receptors determine whether to kill a target or not
normal cells present a
- Ligand for activating (killing) receptor on NK cells
- An MHC class I ligand for the inhibitory receptor
* tolerance
missing self model
- when viruses infect cells, some may inhibit MHC class I expression to evade detection and elimination by CTLs
- loss of MHC molecule expression promotes killing of altered self cell
balanced signals model
- balance of inhibitory vs activating signals determines whether NK is activated or not
- up regulation of stress-induced ligands promotes killing of altered self-cell
