Natural Killer and Cytotoxic T Cells Flashcards
What is the difference between innate and adaptive immune responses?
➝ innate : non-specific, immediate response
➝ Adaptive : highly-specific, delayed
Where do NK and T cells arise from?
➝ common lymphoid progenitor
What kind of cells are NK cells?
➝ innate lymphoid cells
What is the role of cytotoxic lymphocytes?
➝ kill cells infected with bacteria, viruses or parasites
➝ kill tumor cells
Where are MHC proteins found and what do they do?
➝ at the cell surface
➝ form a structure that holds antigenic peptides for surveillance
What cell is MHC I recognised by?
➝ CD8+ cytotoxic T cells
What proteins does MHC I present?
➝ ALl proteins including normal cellular proteins and not just viral
How is does MHC present intracellular proteins?
➝ they are cleaved by the proteasome
➝ transported into the ER
➝ bind to MHC I
➝ transported to the cell surface
How does an infected cell get killed by CD8+ T cells?
➝ viruses infect cells
➝ viral proteins are synthesized in the cytoplasm
➝ peptide fragments are bound to MHC class I
➝ MHC presents the viral peptides to the surface
➝ Cytotoxic T cells recognise viral peptides and kill the infected cells
What is the structure of MHC class I?
➝ Two polypeptides not covalently bound
➝ alpha 3 domain and beta 2 microglobulin are there to provide support to the peptide binding groove
Why haven’t pathogens mutated to avoid MHC presentation?
➝ There are multiple genes of MHC class I ➝ high genetic variability within these genes
Where are the polymorphisms found in MHC?
➝ Upper peptide binding part
How can different peptides bind?
➝ Different amino acids from different alleles means different charges and size and shape of the peptide binding groove
What two things do T cells recognise?
➝ MHC protein
➝ antigenic peptide presented by MHC
How does the TCR bind to MHC and why?
➝ with a diagonal footprint that cuts across both alpha helices with the peptide inbetween
➝ it allows it to make contact with the MHC and the peptide in the middle
Why are co-receptors needed when a cytotoxic T cell interacts with MHC?
➝ the interaction is not particularly strong
What acts as a co-receptor with cytotoxic T cells?
➝ CD8
What does the TCR and CD8 bind to?
➝ TCR binds to the alpha1 and alpha 2 domains
➝ CD8 binds to the support domains alpha 3 and beta 2M
What parts of the MHC is conserved and what part has polymorphisms?
➝ The structural part that binds to CD8 is highly conserved
➝ the part that surrounds the peptide has polymorphisms
Why is the structural part of the MHC highly conserved?
➝ the CD8 will not recognise it if it varies
What are 5 ways that pathogens affect MHC and give examples of which viruses use these methods?
➝ Inhibit MHC-I transcription - adenovirus
➝ Block TAP (HSV)
➝ Retain MHC-I in the ER (HCMV, adenovirus)
➝ Target MHC for disposal ( HCMV)
➝ Downregulate MHC-I from surface - HIV
What are classical NK cells?
➝ large granular lymphocytes that are not T or B cells
What marker do NK cells express?
➝CD56