Natural born killers - NK cells and CD8+ T lymphocytes Flashcards
What are cytotoxic lymphocytes?
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
Why do we need more than 1 type of lymphocyte?
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
What are cytotoxic T cells?
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
What are natural killer cells?
Innate immune cells
Controlled by a balance of signals between different activity and inhibitory receptors on their surface
Broad specificity for target cells
How does a MHC class 1 present itself at the cell surface?
- 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….
How do viruses prevent MHC class 1 from getting to the cell surface?
- 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
How can the immune system detect when MHC-1 has been prevented from getting to the surface by viruses?
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
Describe the MHC gene complex
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
What does the TCR recongise?
- 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
What determines whether if a natural killer cell kills or not?
the balance of inhibitory and activating receptor stimulation
What is the ADCC?
= 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
Compare and contrast cytotoxic T cells and natural killer cells