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
M2 vs M1 macrophages
M2 produce arginase
causes smooth muscle contraction to help remove parasitic worms
M1 have enhanced killing mechansims to deal with intracellular pathogens
- evolved to survive in vesicles
TH1 vs TH2 production
1.dendritic cells rpdouce IL-12
2.activates NK cells to produce IFN-y
= promotes TH1
- Parasites and worms produce soluble antigens presneted by basophils
- basophils secrete IL-4
= promotes TH2
Interleukin that promotes for TH1
IL-12
produced by activated NK cells
Interleukin that promotes for TH2
IL-4
produced by basophils
