12 - Cytotoxicity, Cell Death, and Immunity

Question 1

What is cytotoxicity

Answer 1

Cytotoxicity: Killing of one cell by another, e.g. induction of apoptosis in infected or transformed cells, induced by NK or T cells

Question 2

What is necrosis?

Answer 2

• Necrosis: uncontrolled cell death from infection, injury etc.
• All cell types

Question 3

Programmed cell death

Answer 3

Programmed cell death: originally referred to as
apoptosis
- Occurs in all cell types, important in many cellular processes as well as immunity

Question 4

Death receptors

Answer 4

Death receptors: subset of TNF-receptor superfamily
- Trigger cascade of the caspase enzymes to induce apoptosis
- Slower and later killing event

Question 5

What happens in NK cell killing

Answer 5

• Inhibitory/activating receptor binding forms immunological synapse
• Signals result in actin reorganization and convergence of lytic granules
• Finally, granules fuse with PM and release their contents

Question 6

Example of NK cell killing

Answer 6

e.g. CD95L or TNF- related apoptosis- inducing ligand
(TRAIL) on NK (or Tc) cells, binding to death receptors on target cell

1.Granules polarize towards target
2. Actin rearrangement essential
3. Perforin: bids to phosphatidylcholine

Question 7

Cytotoxic T cell killing

Answer 7

1. paired costimulatory and adhesion molecules LFA-1:ICAM-1, LFA-2:LFA-3
2. activation, proliferation, and differentiation
3. release of perforin and granzymes, polyperforin channel granzymes (proteases to trigger apoptosis

Question 8

Fas/FasL

Answer 8

• Fas/FasL binding: signalling molecules activate caspase cascade
• Fas/FasL: also a means by which TC cells kill each other (fratricide) eliminating effector cells at the end of an immune response

Question 9

Cell death and immunity timeline

Answer 9

1885: Walter Flemming describes morphological features of cell death
1972: Kerr, Wylie & Currie define and characterize apoptosis
- Cell death based on morphological features
2012: proposed that different forms of cell death be defined by quantifiable biochemical parameters. Updated recommendations are made by the
- Nomenclature Committee on Cell Death

Question 10

What happened in 2018?

Answer 10

In 2018, NCCD reclassified regulated cell death (RCD) on the basis of molecular characteristics
- Up to 12 forms of RCD have now been defined, including forms
such as: Necroptosis, Etosis (extracellular traps), Pyroptosis