Natural born killers Flashcards

1
Q

What is innate immunity?

A

• Innate is relatively non-specific/broadly specific and immediate response

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2
Q

What is adaptive immunity?

A

• Adaptive is highly specific and theirs a delayed response

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3
Q

Where do both natural killer cells and T cells both originate from and so what are both?

A

Natural killer cells and T cells both originate from common lymphoid progenitor cells, so both are lymphocytes

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4
Q

What are cytotoxic cells used to destroy?

A

Cytotoxic cells are used to destroy our own cells that are infected with bacteria/viruses/parasites or tumour cells

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5
Q

Where are MHC class proteins found and what do they form?

A

MHC class proteins are found at the cell surface and form a structure that holds antigenic peptides for surveillance by T cells

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6
Q

What cells are MHC class I recognised by?

A

• MHC class I is recognised by CD8.+ cytotoxic T cells

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7
Q

What are all normal and viral proteins presented by?

A

• All normal proteins as well as viral proteins are presented by MHC class I

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8
Q

How do adenoviruses stop their peptides from getting presented on MHC class I?

A

§ Inhibit MHC-I transcription

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9
Q

How does HPV stop their peptides from getting presented on MHC class I?

A

§ Blocks TAP activity
□ This is the transporter which gets peptides from cytoplasm into ER
§ MHC-I remains empty

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10
Q

How does HCMV stop their peptides from getting presented on MHC class I?

A

§ Retains MHC-I in ER or targets MHC-I for disposal from ER

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11
Q

How does HIV stop their peptides from getting presented on MHC class I?

A

§ Downregulates MHC-I from cell surface

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12
Q

What structural domains does MHC class I have?

A

MHC class I has the structural domains alpha-3 and beta2 macroglobulin

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13
Q

What are the structural domains in MHC class I for?

A

○ Largely there to provide support to the peptide binding groove on top

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14
Q

What is MHC class I found on?

A

• MHC class I is found on every nucleated cell

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15
Q

What HLA do humans have?

A

• Humans have HLA-A, B or C

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16
Q

What are MHC class I proteins central to?

A

• MHC class I proteins are central to anti-viral immune responses

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17
Q

Where are polymorphisms found in the MHC protein and what does this decide?

A
• Polymorphisms are found in the upper peptide part of the MHC protein
     § This decides what peptides the MHC class can bind to
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18
Q

What do amino acids in the MHC peptide groove create?

A

• Amino acids in the MHC peptide groove create pockets where the bound peptide can anchor

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19
Q

What do MHC class I and II play a central role in?

A

• MHC class I and II play a central role in the ability of the immune system to distinguish self from non-self

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20
Q

What are the 2 things TCR recognise?

A

• TCRs recognise 2 things:
○ The MHC protein itself
○ The antigenic peptide presented by the MHC protein

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21
Q

How does TCR bind with MHC protein and what does this help the TCR with?

A

• TCR binds with a diagonal footprint that cuts across both alpha helices with the peptide in between
○ This helps TCR to bind to both the MHC and the peptide

22
Q

What is the interaction between the TCR and MHC-I and therefore what is used to make an effective response.

A

• For cytotoxic T cells, the interaction between the TCR and MHC-I isn’t very strong
○ Therefore use CD8 as a co-receptor to make an effective response

23
Q

What domain does TCR bind to and where is it located?

A

• TCR binds to the alpha1alpha2 domains which is at the top of the MHC

24
Q

What does CD8 bind to and what is the reason for?

A

• CD8 bind to the support domains at the bottom of the MHC

§ This is the reason for the lack of polymorphism at the bottom if the MHC, hence highly conserved

25
Q

What are natural killer cells?

A

• Large granular lymphocytes that are not T/B cells

26
Q

What do natural killer cells generally express?

A

• Generally express the cell surface marker CD56

27
Q

What are the 2 major functions of natural killer cells?

A
  1. Cytokine secretion

2. Cytotoxic functions

28
Q

What function was associated with reduced cancer risk?

A

• Medium and high cytolytic function was associated with reduced cancer risk whereas low cytolytic function was associated with increased cancer risk

29
Q

What are killer Ig-like receptors(KIR)?

A

Killer Ig-like receptors(KIR) are innate immune receptors that regulate the activity of natural killer cells

30
Q

What are leukocyte Ig-like receptors?

A

• Leukocyte Ig-like receptors(LILR) are innate immune receptors that regulate the functions of NK cells

31
Q

What happens when a KIR recognises a MHC-I?

A

inhibits NK cells from releasing lytic granules

32
Q

What do some viruses do to evade cytotoxic T cells?

A

• Some viruses down regulate MHC-I as a means to evade cytotoxic T cells

33
Q

What is the loss of MHC-I a common feature of?

A

• Loss of MHC-I is also common feature of tumour cells

34
Q

What happens to KIR if the target cell doesn’t express MHC-I and what does this cause?

A

• If a target cell doesn’t express MHC-I, then there’s no KIR inhibition
§ This causes lytic granules to be released to lyse the target

35
Q

What does inhibitory KIR bind to the same face of as the T cell receptor?

A

• Inhibitory KIR bind to the same face of MHC-I as the T cell receptor

36
Q

Why are KIR polymorphic?

A

• KIR are also polymorphic as KIR genes vary in their presence between individuals

37
Q

What do different MHC-I/KIR combinations show?

A

• Different MHC-I/KIR combinations show disease associations

38
Q

What do natural cytotoxicity receptors(NCR) provide?

A

• These provide activating signals to NK cells but are not well characterised

39
Q

What does NCR 1 bind?

A

• NCR 1 binds viral haemagglutinin

40
Q

What does NCR 2 bind?

A

• NCR 2 binds a ligand that is expressed in tumour cells and upregulated by viral infection

41
Q

What does NCR 3 bind?

A

• NCR 3 binds a ligand that is stress induced

42
Q

How can tumour cells escape the adaptive immune system and what does it make tumour cells more susceptible to?

A
• Tumour cells can escape the adaptive immune system by downregulating the expression of MHC class I
§ Become more susceptible to NK cells
43
Q

What do NK cells and T cells carry?

A

• NK cells and T cells carry granules filled with cytotoxic proteins

44
Q

At what site are cytotoxic granules containing released and what are they?

A

Release cytotoxic granules containing proteins at site of contact with target cells

  1. Perforin
  2. Granzymes
  3. Granulysin
45
Q

What do perforins help deliver?

A

§ Helps deliver contents of granules into cytoplasm of target cells

46
Q

What do granzymes activate?

A

§ Activate apoptosis once in cytoplasm of target cell

47
Q

What does granulysin have and what can it induce?

A

§ Has antimicrobial properties and can induce apoptosis

48
Q

Why must cytotoxic granules be directed?

A

• Must be directed in order to avoid damaging innocent bystander cells

49
Q

What do CD8 cells trigger apoptosis of target cell through?

A

• CD8 cells can also trigger apoptosis of target through Fas/FasL interaction

50
Q

Apoptotic pathway Fas/FasL interaction

A

○ FasL on T cell interacts with Fas protein on target cells
○ Binding trimerizes death domain on Fas protein
○ Interacts with Fas associated death domain(FADD)
○ FADD has a death effector domain(DED) which converts pro-caspase 8 to caspase 8
○ Triggers the extrinsic apoptotic pathway

51
Q

What is Fas/FasL triggered apoptosis used to dispose?

A

• Fas/FasL triggered apoptosis is used to dispose of unwanted lymphocytes

52
Q

What can loss of Fas result in?

A

• Loss of Fas can result in autoimmune lymphoproliferative syndrome(ALPS)