Natural born killers - NK cells and CD8+ T lymphocytes

Question 1

What are cytotoxic lymphocytes?

Answer 1

Are needed to be able to destroy cells infected with bacteria, viruses or parasites and tumour cells

Lymphocytes scanning a target cell surface need to detect changes in protein production inside the target cell

• MHC Class 1 proteins are found at the cell surface
  
  • They form a structure that presents protein fragments at the cell surface for immune surveillance - to see if the cell is non-self
  • Recognised by CD8+ cytotoxic T cells

Question 2

Why do we need more than 1 type of lymphocyte?

Answer 2

To combat infection in the period before T cell response develops

To provide alterative system when a tumour or infected cells evade cytotoxic T cell responses

Provide an additional mechanism for killing infected targets via antibody recognition

Question 3

What are cytotoxic T cells?

Answer 3

CD8+ T cells

• Part of adaptive immune response
• Controlled by a T cell receptor which has high specificity for antigens
• It has a co-receptor = CD8 which attaches to its target antigen and helps stabilise

Question 4

What are natural killer cells?

Answer 4

Innate immune cells

Controlled by a balance of signals between different activity and inhibitory receptors on their surface

Broad specificity for target cells

Question 5

How does a MHC class 1 present itself at the cell surface?

Answer 5

• Antigen proteins enter a proteasome which chops it up into fragments
• The peptide fragments then enter ER, where they come into contact with empty MHC class 1
• If a fragment binds to the MHC class 1, then the whole complex will exit towards cell surface

**these can be normal or toxic antigens**

This is then set up for when viral infection takes place….

Question 6

How do viruses prevent MHC class 1 from getting to the cell surface?

Answer 6

• Inhibit MHC-1 transcription
• Block peptide transcription into the ER
• Retain MHC-1 in ER
• Target MHC-1 for disposal from the ER
• Downregulate MHC-1 from cell surface

Question 7

How can the immune system detect when MHC-1 has been prevented from getting to the surface by viruses?

Answer 7

Through Killer Ig-like receptors (KIR)

• Bind to MHC-1 at surface in a normal healthy cell - sends a negative inhibitory signal into cell saying do not kill this is healthy
• If a virus is inside cells, so lack of MHC-1 on surface, there is nothing for KIR to attach to - so the natural killer cell will kill as has no signal saying not to
• ‘missing-cell’ process

Question 8

Describe the MHC gene complex

Answer 8

MHC gene complex is located on chromosome 6 and contains 3 MHC class 1 proteins and 3 MHC class 2 proteins

They are highly polymorphic

• The variation in class 1 proteins and high genetic variability within these genes may counteract the pathogens ability to evolve and evade immune responses

Polymorphisms are in the upper peptide-binding part of the MHC protein

Question 9

What does the TCR recongise?

Answer 9

• MHC protein itself (hence compatibility…)
• Antigenic peptide presented by MHC protein

Binds with a diagonal footprint that cuts across both alpha helices with the peptide in between

Question 10

What determines whether if a natural killer cell kills or not?

Answer 10

the balance of inhibitory and activating receptor stimulation

Question 11

What is the ADCC?

Answer 11

= antibody-dependent cell-mediated cytotoxicity

• NK cells express a receptor that recognises the Fc portion of antibodies
• This receptor delivers a strong activating signal when it recognises antibodies bound to a cell surface
• Results in lysis of the target cell

Question 12

Compare and contrast cytotoxic T cells and natural killer cells

Answer 12