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Immunology > Natural Born Killers > Flashcards

Natural Born Killers Flashcards

1
Q

What is innate immunity?

A

Innate immunity 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 there is a delayed response.

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3
Q

Where do both NK cells T cells both originate from?

A

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

A

They block TAP activity. This is the transporter which gets the peptides from the cytoplasm into the ER and therefore MHC-1 remains empty.

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9
Q

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

A

downregulates MHC-1 from the cell surface

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10
Q

What structural domains does MGC class I have?

A

MHC class I has the structural domains alpha-3 and beta-2 macroglobulin.

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11
Q

What are the structural domains in MHC class I for?

A

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

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12
Q

What is MHC class I found on>

A

It is found on every nucleated cell

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13
Q

What HLA (human leukocyte antigen) do humans have?

A

HLA- A, B or C

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14
Q

What MHC class I proteins central to?

A

They are central to anti-viral immune responses.

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15
Q

What 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 and this decides what peptides the MHC class can bind to.

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16
Q

What do amino acids in the MHC peptide groove create?

A

They create pockets where the bound peptide can anchor.

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17
Q

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

A

They play a central role in the ability of the immune system to distinguish self from non-self.

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18
Q

What are the 2 things TCR recognise?

A
  1. The MHC protein itself

2. The antigenic peptide presented by the MHC protein

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19
Q

How does TCR bind with MHC protein and what does this help 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.

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20
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.

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21
Q

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

A

TCR binds to the alpha-1-alpha-2 domains which are at the top on the MHC.

22
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 and this is the reason for the lack of polymorphism at the bottom if the MHC, hence highly conserved.

23
Q

What are natural killer cells?

A

Large granular lymphocytes that are not T/B cells

24
Q

What do natural killer cells generally express?

A

Generally, express the cell surface marker CD56

25
Q

What are the 2 major functions of NK cells?

A
  1. cytokine secretion

2. cytotoxic functions

26
Q

What function was associated with reduced cancer risk?

A

The medium and high cytolytic function was associated with reduced cancer risk, whereas low cytolytic function was associated with increased cancer risk.

27
Q

What are the killer Ig-like receptors (KIR)?

A

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

28
Q

What are leukocyte Ig-like receptors?

A

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

29
Q

What happens when KIR recognises a MHC-1?

A

Inhibit NK cells from releasing lytic granules

30
Q

What do some viruses do to evade cytotoxic T cells?

A

Some viruses downregulate MHC-I as a means to evade cytotoxic T cells

31
Q

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

A

This is a common feature of tumour cells

32
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-1 then there’s no KIR inhibition. This causes lytic granules to be released to lyse the target

33
Q

What does inhibitory KIR bind to?

A

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

34
Q

Why are KIR polymorphic?

A

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

35
Q

What do different MHC-1/KIR combinations show?

A

Different MHC-1/KIR combinations show disease associations

36
Q

What do natural cytotoxicity receptors (NCR) provide?

A

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

37
Q

What does NCR 1 bind?

A

NCR 1 binds viral haemagglutinin

38
Q

What does NCR 2 bind?

A

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

39
Q

What does NCR 3 bind?

A

NCR 3 binds a ligand that is stress-induced

40
Q

Hoe 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 and become more susceptible to NK cells

41
Q

What do NK cells and T cells carry?

A

They carry granules filled with cytotoxic proteins

42
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
43
Q

What do perforins help deliver?

A

Contents of the granules into the cytoplasm of target cells

44
Q

What do granzymes activate?

A

They activate apoptosis once in the cytoplasm of target cell

45
Q

What does granulysin have and what can it induce?

A

Has antimicrobial properties and can induce apoptosis

46
Q

Why must cytotoxic granules be directed?

A

Must be directed in order to avoid damaging innocent bystander cells

47
Q

What do CD8 cells trigger apoptosis of target cell through?

A

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

48
Q

Describe the apoptotic pathway Fas/FasL interaction?

A
  • FasL on T cell interacts with Fas proteins on target cells
  • Binding trimerises 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
49
Q

What Fas/FasL triggered apoptosis used to dispose?

A

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

50
Q

What can the loss of Fas result in?

A

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

51
Q

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

A

inhibit MHC-1 transcription?

Immunology (5 decks)

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