Natural born killers - NK cells and CD8+ T lymphocytes Flashcards

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1
Q

What are cytotoxic lymphocytes?

A

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
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2
Q

Why do we need more than 1 type of lymphocyte?

A

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

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3
Q

What are cytotoxic T cells?

A

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
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4
Q

What are natural killer cells?

A

Innate immune cells

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

Broad specificity for target cells

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5
Q

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

A
  • 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….

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6
Q

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

A
  • 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
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7
Q

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

A

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
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8
Q

Describe the MHC gene complex

A

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

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9
Q

What does the TCR recongise?

A
  • 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

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10
Q

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

A

the balance of inhibitory and activating receptor stimulation

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11
Q

What is the ADCC?

A

= 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
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12
Q

Compare and contrast cytotoxic T cells and natural killer cells

A
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