Natural Born Killers: NK Cells and CD8+ T Lymphocytes Flashcards
(46 cards)
How are CD8 T cells and NK cells similar?
Both Cytotoxic T cells and natural killer cells essentially do the same job but as part of different types of immunity
Which cell is a major part of the innate immune system?
NK cells: non-specific (or broadly specific), immediate response
Which immune cell is an integral part of the adaptive immune system?
T cells: highly-specific, delayed response`
Where do T cells and NK cells originate?
Both arise from common lymphoid progenitor cell
Both part of lymphocyte lineage
What is the role of cytotoxic CD8+ T cells?
We need cytotoxic cells as a means to destroy
- Cells infected with bacteria, viruses or parasites
- Tumour cells
What is the role of MHC Class I molecules?
MHC class I proteins are found at the cell surface and form a structure that holds antigenic peptides for surveillance by T cells
How are MHC I molecules recognised?
MHC-I = recognised by CD8+ cytotoxic T cells
How do MHC molecules aid pathogen recognition?
Intracellular proteins are presented at the cell surface by MHC class I
Which proteins are presented on MHC I molecules?
Proteins expressed within a cell (whether healthy, mutated or resulting from infection) are processed and presented on MHC class I proteins
Describe the structure of MHC I molecules
Humans: HLA-A, -B, -Ctwo polypeptides, non-covalently bound:
𝛂3 domain and ꞵ2 microglobulin provide support to peptide binding group on top
2 𝛂 helices at sides of groove and ꞵ sheet at the bottom forms base
Which cells express MHC Class I molecules?
all nucleated cells
Why don’t we see many pathogens mutating to avoid antigen presentation
MHC class I proteins are central to antiviral immune responses
- Multiple genes (e.g. 2 copies each of HLA-A, B + C)
- High genetic variability within these genes
Outline what enables MHC Class I variability
Polymorphisms in upper peptide-binding part of MHC protein - provide variation in the peptide binding groove
Where on the MHC molecule do pathogenic peptides bind?
Amino acids in the MHC peptide binding groove create pockets where the bound peptide can “anchor”
How do polymorphisms provide variation in MHC I molecules?
By substituting different amino acids, we get different charges (+ve/-ve) between MHCs, different sizes and shapes between pockets ⇒ different peptides bind to different MHC alleles
What substances do TCRs recognise?
TCR recognise two things
- MHC protein itself (hence compatibility)
- Antigenic peptide presented by MHC protein
TCR recognises both MHC protein and peptide antigen being presented by it
How does MHC structure allow T cel recognition?
Binds with a diagonal footprint that cuts across both alpha helices with the peptide in between - allows T cell recognition
WHy can CD8 and TCRs bind to MHC simultaneously?
Distant binding sites allow CD8 and TCR to bind MHC-I at the same time
What is the role of CD8 binding to MHC?
CD8 acts as a co-receptor for MHC-I, and is required for the T cell to make an effective response
Where on the MHC I molecule do TCRs bind?
TCR binds to the α1α2 domains
Which part of the MHC I molecule do CD8 peptides bind?
CD8 binds to the support domains (α3 and β2m) - very highly conserved region to ensure CD8 binding
- Similar situation for CD4 and MHC-II
Outline how different viruses may subvert MHC functions
Microbes may subvert MHC upregulation by:
- Inhibit MHC-I transcription (adenovirus)
- Block TAP activity (HSV)
- Retain MHC-I in endoplasmic reticulum (adenovirus, HCMV)
- Target MHC-I for disposal from ER (HCMV)
- Downregulate MHC-I from cell surface (HIV)
What are NK cells?
Classical NK cells are large granular lymphocytes that are not T or B cells
Describe the protein structures of classic NK cells
- Don’t express TCR (CD3) or B cell receptor
- Express cell surface marker CD56
- CD3- CD56+
