L8 - Immune response to Intracellular pathogens Flashcards
NK cells activation strength depends on what
balance of inhibitory and activator signal
inhibitory receptor binds to MHC-1
activator ligand binds to ligand upregulated due to stress
= NK cells kill cells lacking MHC 1
= less MHC 1 = stronger response
NK cells role in early host defence
first line of defence while adaptive immunity gets ready
2 ways that stimulate NK cells to release cytotoxic granules
lack of MHC 1 /inhibitory signal
Antibodies - bind to Fc region of bound antibody
2 subsets of NK cells
Bright:
high in CD56
low levels of CD16
= high cytokine production but POOR cytotoxic effects
Dim:
low CD56
High CD16
= low cytokine production but GOOD cytotoxic
CD16 binds to cross-linked Fc regions
- dim/bright due to CD56 being flourescemtly labelled
balance of viral mechansism to evade Nk and CD8 cells
bind and restrain MHC 1 in endoplasmic reticulum to avoid CD8
bUT upregulate mimic proteins that look like MHC for NK
name of theory that NK cells are activated due to lack of MHC 1
Missing self hypothesis
decsribe the relationship between IL-2 and CD25 on T cell activation
all T cells express gamma and beta chains of IL-2 receptors
allows binding of IL-2 but withw LOW affinity
on activation the alpha chain/CD25 is upregulated
completes the receptor = binds IL-2 with high affinity
= survival/proliferative signal
describe how IL-2 production on activation of T-cells is important
IL-2 activates the T-cell it was made by BUT also surrounding T-cells
only 2 signals are required to activate T-cells following initial activation = TCR and cytokine
which of the 3 signals can T cells not do on their own
Co-stimulatory - Cd28-B7
reason APC are vital for inital activation = as T cells do not have B7
how do CD8 T-cells scan for infected cells (non-specific and specific)
T cells roll along cells
form non-specifc adhesions as they move by L-selectins
if adheses to infcted molecule - TCR binds withb high affinity
what happenes to cytotoxic granules when a T-cell makes a specifc interaction with a infected cell
polazrised
moveed to surface of cell
MTOC - microtubule organisng centre
how do T-cells cause ‘sequential killing’ of multiple targets
T cell rolls onto the next infected cell killing it
how do Serglycin and graneznymes work when released by CD8 T-cell (BID and caspase)
serglycin acts as scaffolf to help oyther proteins into infected cell
- graneznyme B cleaves pro-caspase 3
- caspase 3 cleaves inhibitor of CAD ( caspase activated DNase)
- CAD degrades DNA
- BID cleaved to TBID (truncated)
- disrupts mitochondrial membrane
- Cytochrome C released = activates apoptosome
targets of TBID and caspase 3 when cleaved by graneznymes in apoptosis - CD8 T cells
Caspase-3 = DNA
TBID = mitochondrial membrane/Cytochrome C release
what is the end product of TBID releasing cytochrome C into the cytoplasm - intrinsic apoptic pathway
caspase 3 prodcued by apoptosome
= cleaves ICAD –> CAD
= cleaves DNA
formation of apoptosome by TBID and cytochrome C
- mitochondria release Cytochrome C into cytoplasm
- binds to Apaf-1
- complex assembles apoptosme and activates pro-caspase 9
- cleaves and activates capsase 3
- caspase 3 cleaves ICAD
= degrades DNA
describe the extrinsic apoptic pathway - Fas ligand (FasL)
- Fas-L on CD8 t cells binds to Fas
- comformational change of Fas causing recruitment of death domain proteins
- activates caspase 3
- Cleaves ICAD—> CAD
= DNA degradation
what signals to macrophages that an infected cell is undergoing apoptosis
phospholipids flip out of bilayer
which type of T cell activate M1 macrophages
T-helper 1
how do TH1 cells activate M1 macrophages to deal with pathogens living in vesicles
- proteins produced by interanl pathogens are presented by MHC 2
- T cells bind and activate via CD40 and IFNy
what happenes tro active M1 macrophages following TH1 cells
phagosomes fuse with lysosomes
production of recative oxygen and nitrogen species (ROS)
MHC 2 expression increase
roles of TH1 cells in response to intracellular infections
- IFN-y and CD40 cause M1 macrophage activation
- Fas ligand induces apoptosis of macrophages too far gone
- IL-2 produced activates naive T cells
what are granulomas
multi-nucleated giant cell formations
when infected macrophages are resistant to enhanced macrophage ability when activated by TH1 cell
= wall of T cells surround it to prevent further spread but cannot actually kill it
role of TH2 cells against helminths/parasitic worms
- activate M2 macrophages via IL-4
= produces arginase = incraesed smooth muscle contraction - mast cell recruitment
= mast cells have IgE bound
= recruit inflammatory cells and remodel mucosal layer
