L8 - Immune response to Intracellular pathogens

Question 1

NK cells activation strength depends on what

Answer 1

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

Question 2

NK cells role in early host defence

Answer 2

first line of defence while adaptive immunity gets ready

Question 3

2 ways that stimulate NK cells to release cytotoxic granules

Answer 3

lack of MHC 1 /inhibitory signal

Antibodies - bind to Fc region of bound antibody

Question 4

2 subsets of NK cells

Answer 4

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

Question 5

balance of viral mechansism to evade Nk and CD8 cells

Answer 5

bind and restrain MHC 1 in endoplasmic reticulum to avoid CD8

bUT upregulate mimic proteins that look like MHC for NK

Question 6

name of theory that NK cells are activated due to lack of MHC 1

Answer 6

Missing self hypothesis

Question 7

decsribe the relationship between IL-2 and CD25 on T cell activation

Answer 7

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

Question 8

describe how IL-2 production on activation of T-cells is important

Answer 8

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

Question 9

which of the 3 signals can T cells not do on their own

Answer 9

Co-stimulatory - Cd28-B7

reason APC are vital for inital activation = as T cells do not have B7

Question 10

how do CD8 T-cells scan for infected cells (non-specific and specific)

Answer 10

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

Question 11

what happenes to cytotoxic granules when a T-cell makes a specifc interaction with a infected cell

Answer 11

polazrised

moveed to surface of cell

MTOC - microtubule organisng centre

Question 12

how do T-cells cause ‘sequential killing’ of multiple targets

Answer 12

T cell rolls onto the next infected cell killing it

Question 13

how do Serglycin and graneznymes work when released by CD8 T-cell (BID and caspase)

Answer 13

serglycin acts as scaffolf to help oyther proteins into infected cell

1. graneznyme B cleaves pro-caspase 3
2. caspase 3 cleaves inhibitor of CAD ( caspase activated DNase)
3. CAD degrades DNA
4. BID cleaved to TBID (truncated)
5. disrupts mitochondrial membrane
6. Cytochrome C released = activates apoptosome

Question 14

targets of TBID and caspase 3 when cleaved by graneznymes in apoptosis - CD8 T cells

Answer 14

Caspase-3 = DNA

TBID = mitochondrial membrane/Cytochrome C release

Question 15

what is the end product of TBID releasing cytochrome C into the cytoplasm - intrinsic apoptic pathway

Answer 15

caspase 3 prodcued by apoptosome

= cleaves ICAD –> CAD

= cleaves DNA

Question 16

formation of apoptosome by TBID and cytochrome C

Answer 16

1. mitochondria release Cytochrome C into cytoplasm
2. binds to Apaf-1
3. complex assembles apoptosme and activates pro-caspase 9
4. cleaves and activates capsase 3
5. caspase 3 cleaves ICAD
   = degrades DNA

Question 17

describe the extrinsic apoptic pathway - Fas ligand (FasL)

Answer 17

1. Fas-L on CD8 t cells binds to Fas
2. comformational change of Fas causing recruitment of death domain proteins
3. activates caspase 3
4. Cleaves ICAD—> CAD

= DNA degradation

Question 18

what signals to macrophages that an infected cell is undergoing apoptosis

Answer 18

phospholipids flip out of bilayer

Question 19

which type of T cell activate M1 macrophages

Answer 19

T-helper 1

Question 20

how do TH1 cells activate M1 macrophages to deal with pathogens living in vesicles

Answer 20

1. proteins produced by interanl pathogens are presented by MHC 2
2. T cells bind and activate via CD40 and IFNy

Question 21

what happenes tro active M1 macrophages following TH1 cells

Answer 21

phagosomes fuse with lysosomes

production of recative oxygen and nitrogen species (ROS)

MHC 2 expression increase

Question 22

roles of TH1 cells in response to intracellular infections

Answer 22

1. IFN-y and CD40 cause M1 macrophage activation
2. Fas ligand induces apoptosis of macrophages too far gone
3. IL-2 produced activates naive T cells

Question 23

what are granulomas

Answer 23

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

Question 24

role of TH2 cells against helminths/parasitic worms

Answer 24

1. activate M2 macrophages via IL-4
   = produces arginase = incraesed smooth muscle contraction
2. mast cell recruitment
   = mast cells have IgE bound
   = recruit inflammatory cells and remodel mucosal layer

Question 25

M2 vs M1 macrophages

Answer 25

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

Question 26

TH1 vs TH2 production

Answer 26

1.dendritic cells rpdouce IL-12
2.activates NK cells to produce IFN-y

= promotes TH1

1. Parasites and worms produce soluble antigens presneted by basophils
2. basophils secrete IL-4

= promotes TH2

Question 27

Interleukin that promotes for TH1

Answer 27

IL-12
produced by activated NK cells

Question 28

Interleukin that promotes for TH2

Answer 28

IL-4

produced by basophils