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Sem 2: Immuno > Block 3- NK cells TOKA > Flashcards

Block 3- NK cells TOKA Flashcards

1
Q

Where do NK cells originate from?

A

Bone marrow

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2
Q

What is the lifespan of NK cells?

A

~ 1 week

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3
Q

Where can NK cells normally be found?

A

Blood, spleen, and liver

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4
Q

What happens to NK cells when an inflammatory reaction is underway?

A

NK cells migrate to tissues in large #’s to the site of inflammation

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5
Q

True or False: NK cells have antigen receptors generated through gene segment rearrangement

A

FALSE. NK cells do not have antigen receptors

Does not possess receptors generated through gene segment rearrangement

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6
Q

What are chemotactic receptors and how do they affect NK cells?

A

CCR etc

Allows NK cells to move from one area to another

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7
Q

What are cytokine receptors and how do they affect NK cells?

A

IL-1R, etc

Activates NK cells

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8
Q

What are adhesion receptors and how to they work with NK cells?

A

CD2, CNAM-1, B1 integrins, B2 integrins

Helps NK cells to adhere to the endothelium of blood vessels and exit to get to site of inflammation

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9
Q

What are the cell trafficking receptors on NK cells?

A

Chemotactic, cytokine, and adhesion receptors

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10
Q

What is the morphology of NK cells?

A

Referred to as Large Granular Lymphocytes (LGL)

they contain granules that contain molecules for cytotoxicity

Lytic granules kill virus infected cells

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11
Q

What is the role of NK cells in innate immunity?

A
  1. Kills/lysis of VIRUS-INFECTED, TUMOR, and STRESSED cells
  2. Produce cytokines and chemokines that help regulate other cells
  3. Activate macrophages through secretion of cytokines
  4. Also can help control hematopoiesis
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12
Q

What is an “abnormal cell” ?

A

A cell that is

  1. stressed
  2. infected
  3. or has an altered expression of certain cell surface markers
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13
Q

What do all normal, nucleated cells express on their cell surface?

A

MHC1

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14
Q

What happens to the cell surface in virus or tumor infected cells?

A

MHC1 is supressed or failed to express

Infected cells express stress proteins instead that can be recognized by NK cells

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15
Q

What are MICA and MICB?

A

stress proteins that are highly expressed on the surface of stressed cells

alerts NK cells to kill

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16
Q

What type of recognition receptors do NK cells express?

A
  1. Activating receptors
  2. Inhibitory receptors
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17
Q

How do NK cells recognize abnormal cells?

A

Using Activating and Inhibitory Nk cell receptors

18
Q

What happens if a high level of activating signals are expressed?

A

Activated NK cell to kill target cell

this happens when no MHC1 is found on target cell

19
Q

What happens if there is a strong inhibitory signal?

A

NK cells will preserve the cell instead of kill

this happens when a normal MHC1 is expressed on the target cell and there are no stress markers

20
Q

What is the dominating NK receptor and how does it work?

A

Inhibitory receptor dominates and blocks activating signal

this helps prevent NK cells from killing normal cells

21
Q

What are some activating receptors on NK cells?

A

NKp46

CD16

NKG2D

22
Q

What do inhibitory receptors on NK cells do?

A

They recognize MHC1 molecules expressed on normal cells and preserve them instead of kill them

23
Q

What happens in there is a reduction of lack of MHC1 expression on a cell?

A

renders a cell vulnerable to destruction by NK cells

24
Q

What are some inhibitory receptors on NK cells?

A

CD94/NKG2A

25
Q

How do NK cells and macrophages work together?

A
  1. Macrophage releases IL-12
  2. IL-12 activated NK cell
  3. Activated NK cell secretes IFN-y
  4. IFN-y increases macrophage ability to phagocytose microbes
26
Q

What the mechanisms for NK cell cytotoxicity/killing? and what is the end result?

A
  1. Perforin-dependent mechanism
  2. CD95/CD95L (Fas/FasL) mechanism
  3. CD16 killing pathway (ADCC-Antibody dependent cellular cytotoxicity)

End result of all 3 pathways are APOPTOSIS

27
Q

Explain the perforin-dependent mechanism of the NK cell

A

When activating and stress molecules bind to NK cells it triggers the release of PERFORIN contained in the granules

PERFORIN creates a lesion in the target cell membrane and makes a perforin channel

Perforin channel triggers release of GRANULYSIN, NK-LYSIN and FRAGMENTIN (protease) to be released from NK cell

These granzymes pass through the perforin membrane and induce APOPTOSIS

28
Q

What enzymes are contained in the granules of NK cells?

A
  1. Perforin
  2. Granulysin
  3. NK lysin
  4. Fragmentin (protease)
29
Q

Explain the CD95/CD95L (Fas/FasL) mechanism of the NK cell

A

NK cells normally express CD95L (FasL) on the cell surface

  1. Target cells show an increased expression of CD95 (Fas)
  2. CD95L on NK cell surface recognizes and binds to CD95 on the target cell which induces APOPTOSIS
30
Q

Explain the CD16 (ADCC) killing pathway in NK cells

A

CD16 acts as a Fc receptor on NK cells

This pathway only occurs when antibodies are present

When antibodies are present they bind to an antigen on the infected cell

This alerts the CD16 (Fc) receptor on NK cells to bind to the antibody which is bound to the antigen and induces APOPTOSIS

Antibody kinda acts like opsonization to alert the NK cell to come kill

31
Q

What are Lymphokine activated killer cells (LAK)?

A

when isolated NK cells are mixed with cytokines IN VITRO they lead to LAKs that have an increased cytotoxic capacity

highly cytotoxic cells

used in immunotherapy of tumors

32
Q

What is the relevance of foot and mouth disease in swine to NK cells?

A

This virus INHIBITS NK cell cytotoxicity instead of enhances its ability to kill

So this tends to be deadly virus in swine

33
Q

Where do NKT cells originate from?

A

Same lineage as T cells, thymic origin

34
Q

What are some functions of NKT cells?

A

makes up 1% of the peripheral blood mononuclear cells

specifically directed against only few pathogens

does not develop memory

links T cells to NK cells

plays a role in ALLERGIES, ANTI-TUMOR immunity, AUTOIMMUNITY, and ANTIMICROBIAL immunity

CD4+ or CD4- CD8-

35
Q

How are NKT cells activated?

A

by IL-15

36
Q

What do NKT cells express?

A

a/B TCRs

NK1.1 receptors

KCR family receptors

37
Q

What do most NKT cells recognize?

A

glycolipid antigens on bacteria

38
Q

What do NK DCs express?

A

NK1.1

CD11c

39
Q

Where are NK DCs found?

A

Spleen, liver, lymphnodes, and thymus

40
Q

What is the function of NK DC cells?

A
  1. Lyse tumor cells
  2. Present antigens to naive T cells
  3. Produce IFNy upon stimulation through TLR9
  4. Link the innate and adaptive immunity

Sem 2: Immuno (17 decks)

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