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Natural Killer Cells Flashcards

1
Q

Where do natural killer cells originate and where are they found?

A

originate from bone marrow and are found in the blood, spleen, and liver.

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2
Q

When to NK cells migrate to tissues?

A

migrate to tissues only when an inflammatory reaction is underway

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3
Q

What receptors do NK cells have?

A
  • Cell trafficking receptors/chemokine receptors
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4
Q

What are the functions of NK cells?

A
  • secrete cytokines that are important for regulation of the immune response
  • Kill abnormal cells
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5
Q

What do the killing mechanisms of NK cells depend on?

A
  • Killing mechanisms depend on either perforin system or the Fas/FasL interaction
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6
Q

How are NK cells identified?

A
  • by expression of CD56, CD16, and lack of CD3 (humans and mice)
  • no exclusive marker but CD2+/CD8+/CD3- are used (pigs)
  • CD335 (bovine)
  • granules
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7
Q

What is the role of NK cells in innate immunity?

A

kill cells which are stressed, infected with virus or tumor cells - cells that have been deemed abnormal

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8
Q

What happens after NK cells have been activated with cytokines such as IL-2 and IFNy?

A

they become lymphokine activated killer cells (LAK)

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9
Q

What are lymphokine activated killer cells (LAK)?

A

highly cytotoxic cells and are a potential tool in immunotherapy of tumors

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10
Q

How do NK cells recognize abnormal cells?

A
  • abnormal cell has been stressed by any means (eg: infected, transformed cell (tumor)
  • Stressed cells alter the expression of certain cell markers such as MHC (major histocompatibility complex)
  • MHC I chain related A (MIC A) and MIC B are highly expressed on surface of stressed/abnormal cells
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11
Q

How is MHC I expression changed in stressed/abnormal cells?

A

expression is suppressed or not expressed at all

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12
Q

What types of receptors do NK cells have?

A
  • activating receptors

- Inhibitory receptors

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13
Q

True or False? Activation of NK cells is regulated by a balance between signals from activating receptors and inhibitory receptors.

A

True

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14
Q

What does a high level of activating receptors lead to?

A

killing of the target cell

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15
Q

True or False? In a normal cell, activating signals are usually blocked by inhibitory signals.

A

True - prevents their death

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16
Q

NK cell receptors that recognize the MHC class I molecule belong to what family?

A

Killer cell immunoglobulin-like receptor family (KIRs) or Killer cell lectin-like receptors (KLRs) in mice rats and horses.

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17
Q

What are killer cell immunoglobulin-like receptors (KIRs)?

A

they are type I transmembrane proteins that are highly polymorphic and are expressed on NK cells and subsets of lymphocytes

18
Q

What is NKG2D?

A

A lectin-like receptor expressed by NK cells

- recognizes stress proteins such as MICA, MICB, etc.

19
Q

High expression of stress proteins allows binding of NKG2D which overrides what?

A

the inhibitory signals through MHC I and permits NK cell cytotoxicity

20
Q

What is CD16?

A

An Fc receptor expressed on NK cells allowing them to recognize target cells through an antibody dependent pathway

21
Q

How does CD16 lead to NK cytotoxicity?

A

antibodies bind to an antigen on an infected cell, NK cells bind to antibodies through CD16 leading to NK cell cytotoxicity

22
Q

What are the important activating receptors of NK cells?

A
  • NKp46
  • CD16
  • NKG2D
23
Q

What do inhibitory receptors on NK cells do?

A

recognize MHC-I molecules expressed on normal cells

24
Q

What are the important inhibitory receptors of NK cells?

A

CD94/NKG2A

25
Q

What are the effector functions of NK cells?

A

Lysis of infected, stressed, or transformed cells (abnormal cells) and activation of macrophages

  • ADCC against tumor cells
  • Destruction of tumor cells
  • Destruction of virus-infected cells
  • Destruction of bacteria and fungi
  • Control of hematopoiesis
  • GVH disease
26
Q

What is the perforin-dependent mechanism of NK cell cytotoxicity?

A
  • once triggered the NK cell releases perforin from its granules
  • perforin then creates a lesion in the target cell membrane - perforin channels
  • later granulysin, NK-lysin (granzymes) and fragmentin (protease) are released from cytotoxic granules and passes into perforin channels
  • Granzymes and the protease induce apoptosis of the target cell
27
Q

What is the CD95/CD95L (CFas/FasL) mechanism?

A
  • NK cells normally express CD95L (FasL) on the cell surface
  • Target cells (abnormal cells) may have increased expression of CD95 (Fas)
  • Binding of CD95L on the NK to CD95 on the target cell induces apoptosis of the target cell
28
Q

What does ADCC stand for?

A

Antibody dependent cellular cytotoxicity

29
Q

What are the steps involved in antibody-dependent cellular cytotoxicity?

A
  1. Antibody binds antigens on the surface of target cell
  2. Fc receptors on NK cell recognize bound antibody
  3. Cross-linking of Fc receptors signals the NK cell to kill the target cell
  4. Target cell dies by apoptosis
30
Q

What is redirected lysis or reverse ADCC?

A

target cells expressing Fc receptors may be killed through ADCC if the Fc receptor binds an antibody that recognizes an activating receptor

31
Q

What is redirected inhibition

A

target cells expressing Fc receptors may NOT be killed through ADCC if the Fc receptor binds an antibody that recognizes an inhibitory receptor

32
Q

What are NK cells activated by?

A

cytokines such as IL-1, IL-2, IL-12, etc. and type I and II IFNs

33
Q

What are lymphokine activated killer cells?

A

NK cells that have been treated with cytokines

34
Q

What are natural killer T cells? (NKT)

A
  • properties similar to NK cells and T lymphocytes
  • thymic origin (same as T cells)
  • specificity is directed towards only a few pathogens
35
Q

What do natural killer T cells express?

A
  • an invariant alpha/beta TCR
  • NK1.1 and other KLR family receptors
  • mostly they are CD4+ cells or may be double negative CD4-/CD8-
36
Q

What do natural killer T cells (NKTs) recognize?

A

mostly glycolipid antigens on bacteria

37
Q

What are natural killer T cells activated by?

38
Q

What do natural killer T cells do?

A
  • do not develop into memory cells
  • serve to link the T cell system and NK cells
  • play a role in allergies, antitumor immunity, autoimmunity, and antimicrobial immunity
39
Q

What are Natural killer dendritic cells (NK DCs)?

A

dendritic cells that share some properties with NK cells and are present in the spleen, liver, lymph nodes, and thymus

40
Q

What do Natural killer dendritic cells (NK DCs) express?

A
  • NK1.1 (an NK cell marker)

- CD11 ( a DC marker)

41
Q

What do Natural killer dendritic cells (NK DCs) do?

A
  • spontaneously lyse tumor cells
  • can present antigen to native T cells
  • produce large ammount of IFNy upon stimulation through TLR9
  • link the innate and adaptive immunity

Immunology (8 decks)

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