Natural Born Killers: NK Cells and CD8+ T Lymphocytes Flashcards
1
Q
Describe the origin of NK and T cells
A
- Both arise from common lymphoid progenitor cell
- Both part of the lymphocyte lineage
2
Q
What is the role of cytotoxic lymphocytes
A
- Need it to be able to destroy: infected cells and tumour cells
- Lymphocytes scanning a target cell surface need to detect changes in protein production inside that target cell
3
Q
What are the key functions of Cytotoxic T cells
A
- Cytotoxic adaptive immune cells
- Kill virally infected targets
- Kill tumour cells
- Controlled by T cell receptor recognition, with CD8 acting as a co-receptor
- Highly specific
4
Q
What are the key functions of Natural killer cells
A
- Cytotoxic innate immune cells
- Kill virally infected targets
- Kill tumour cells
- Controlled by a balance of signals between different activating and inhibitory receptors on their surface
- Broad specificity for target cells
5
Q
Why do we need more than one type of cytotoxic lymphocyte
A
- To combat infection in the period before a T cell response develops
- To provide an alternative system when a tumour or infected cells evade Cytotoxic T cell responses
- To provide an additional mechanism for killing infected targets via antibody recognition
6
Q
What are some consequences of low NK cells
A
Correlates with severe disseminating herpesvirus infections
7
Q
Describe the role of MHC class 1
A
- Lymphocytes scanning a target cell surface need to detect changes in protein production inside that target cell
- MHC class I proteins are found at the cell surface
- Form a structure that presents protein fragments (peptides) at the cell surface for immune surveillance
- Recognised by CD8+ cytotoxic T cells
8
Q
How are intercellular protein presented on MHC class 1
A
- Proteins are processed in the proteasome and enter the endoplasmic reticulum.
- Binds with MHC 1 at the ER and makes its way to the cell surface to be presented
9
Q
Describe the structure of MHC class 1
A
- Peptide binding cleft where the peptide fragments are bound
- “Hot dog bun structure”
10
Q
Why do we have highly polymorphic HLA
A
- Pathogens can evolve to evade immune responses
- Variation in MHC class I proteins - Multiple genes (e.g. two copies each of HLA-A, B and C) and high genetic variability within these genes may counteract this across populations
11
Q
What is the result of MHC polymorphism
A
- Variance seen in the upper peptide binding groove
- Many different pockets and differences in charges and size of binding region
- Variance in peptides that can anchor within pockets
12
Q
How does TCR bind MHC class 1
A
- TCR recognises both the
MHC protein and the
peptide antigen being
presented by it - Binds with a diagonal
footprint that cuts across
both alpha helices with
the peptide in between
13
Q
what is the role of CD8 in MHC class 1 binding
A
- CD8 acts as a co-receptor for MHC-I, and is required for the T cell to make an effective response
- TCR binds to the a1a2 domains
- CD8 binds to the support domains (a3 and b2m)
14
Q
How can pathogens subvert MHC-1 presentation
A
- Inhibit MHC-I transcription (adenovirus)
- Block peptide transport into the endoplasmic reticulum (HSV)
- Retain MHC-I in endoplasmic reticulum (adenovirus, HCMV)
- Target MHC-I for disposal from the endoplasmic reticulum (HCMV)
- Downregulate MHC-I from cell surface (HIV)
15
Q
What is the function of Killer Ig-like receptors (KIR)
A
- When KIR recognise MHC-I they inhibit NK cells from releasing lytic granules
- Some viruses down regulate MHC-I as a means to evade cytotoxic T cells, loss of MHC-I is also a common feature of tumour cells
- If a target cell does not express MHC-I then there is no KIR inhibition, lytic granules will be released to lyse the target
- This mechanism is known as “missing self”
