HOW DO WE ELIMINATE PATHOGENS THAT LIVE INSIDE CELLS?

Question 1

which cells work agaisnt:

1. cytoplasm? (2)
2. vesicular?

Answer 1

1. cytoplasm: cytotoxic T cells (AKA CD8 T cells), NK cells
2. vesicular: T cell dependent macrophage activation

Question 2

what do we call the immune response that targets intracellular pathogens?

Answer 2

cell mediated immune response

Question 3

which MHC-class recognise CD8 cells?

Answer 3

MHC-Class I

Question 4

how do CD8 / cytotoxic T cells recognise pathogensi on a cell? what happens after

Answer 4

• CD8 T cells have a T cell receptor (TCR) and the CD8 co-receptor
• they kill pathogen infected cells and tumour cells by:
• recognises peptide-MHC-I combination that has been presented on the cell (its the same peptide that the dendritic cell initiailly caused clonal expansion to occur by)
• *- cell death by apoptosis.**
  i) nuclear blebbing
  ii) alteration in cell morophology
  iii) shedding of small membrane vesciles
  iv) apoptotic bodies removed by phagocytosis

Question 5

do cytotoxic T cells / CD8 cells kill one cell or multiple cells?

Answer 5

CD8 T cells can kill repeatedly.

Question 7

how do cytotoxic cells induce apoptosis?

Answer 7

have lytic granules (modified lysosomes), containing:

• *- perforin:** forms pores in cell membrane
• granzymes: bind to proteins in cell membrane to get into cell and then: proteases start chopping up proteins in cell.

= apoptosis

Question 8

what is the mechanism for cytotoxic / CD8 cells knowing which exact target cells to bind to?

Answer 8

• CD8 cell comes close to potential target cell
• creates a non-specific adhesion with the target cell
• then, the TCR binds with MHC-I (which holds pathogen peptide)
• once activated by TCR, get reorganisation of the microtubule organising centre, and GA, lytic granules in the CD8 cell, to line up close to TCR-MHC-I
• lytic granule release occurs
• apoptosis

Question 9

what are NK cells? - what type of cells are they?

how do they kill cells/

which part of immune system are they part of?

Answer 9

Natural Killer cells: innate immune system

- lymphocytes
- DO NOT have antigen-specific receptors :o
- have lytic granules in them.

kill cells in same method as CD8 cells (using perforin and granzymes and inducing apoptosis)

Question 10

what is difference between resting NK and activated NK cells?

what activated by?

Answer 10

• Resting NK cells: can kill cells

ACTIVATED BY CYOTKINES:

- ‘activated’ NK cell: kill 20-100 x more efficiently. produce more lytic granules and IFN-y

Question 11

how do activated NK cells know that a cell is infected? concept of missing self H:?

Answer 11

use: missing-self hypothesis:

• recognition of ‘self’ = inhbition of killing by NK cells
• recongiition of ‘missing-self’ = killing by NK cells (if not from self - could be from transplant, OR if pregnant - also ‘not from self’ from embryo cells)

Question 12

what happens when NK cell recognises cell as self or not self?

when does an NK cell cause apoptosis?

Answer 12

• (REMEMBER: NK CELLS DO NOT HAVE HAVE ANTIGEN RECEPTORS)*
• NK cell recognises that the MHC-I molecules is from own body -> inhib. receptor on NK cell switches off the NK cell

or

• NK cell recognises that the MHC-I molecules is from pathogen (not self) -> inhib. receptor on NK cell still switches off the NK cell
  therefore - cytotoxic cells come along instead and kill

BUT: some viruses cause MHC-I cells to be trapped inside the pathogen infected - so cant recognise it.
- but because the MHC-I cells arent present on infected cell, the inhibitory receptors on the NK cells dont recognise the cell as self - cause apoptosis.

Question 13

are inhibitory or activating receptors more important on NK cells?

Answer 13

inhibitory is more important (like a break on a car, need to take these off before accelerating - activating receptors are the accelerators)