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Natural Killer Cells Flashcards

(41 cards)

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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)?

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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?

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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?

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A

the inhibitory signals through MHC I and permits NK cell cytotoxicity

20
Q

What is CD16?

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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?

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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?

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A
  • NKp46
  • CD16
  • NKG2D
23
Q

What do inhibitory receptors on NK cells do?

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A

recognize MHC-I molecules expressed on normal cells

24
Q

What are the important inhibitory receptors of NK cells?

25
What are the effector functions of NK cells?
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
What is the perforin-dependent mechanism of NK cell cytotoxicity?
- 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
What is the CD95/CD95L (CFas/FasL) mechanism?
- 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
What does ADCC stand for?
Antibody dependent cellular cytotoxicity
29
What are the steps involved in antibody-dependent cellular cytotoxicity?
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
What is redirected lysis or reverse ADCC?
target cells expressing Fc receptors may be killed through ADCC if the Fc receptor binds an antibody that recognizes an activating receptor
31
What is redirected inhibition
target cells expressing Fc receptors may NOT be killed through ADCC if the Fc receptor binds an antibody that recognizes an inhibitory receptor
32
What are NK cells activated by?
cytokines such as IL-1, IL-2, IL-12, etc. and type I and II IFNs
33
What are lymphokine activated killer cells?
NK cells that have been treated with cytokines
34
What are natural killer T cells? (NKT)
- properties similar to NK cells and T lymphocytes - thymic origin (same as T cells) - specificity is directed towards only a few pathogens
35
What do natural killer T cells express?
- 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
What do natural killer T cells (NKTs) recognize?
mostly glycolipid antigens on bacteria
37
What are natural killer T cells activated by?
IL-15
38
What do natural killer T cells do?
- 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
What are Natural killer dendritic cells (NK DCs)?
dendritic cells that share some properties with NK cells and are present in the spleen, liver, lymph nodes, and thymus
40
What do Natural killer dendritic cells (NK DCs) express?
- NK1.1 (an NK cell marker) | - CD11 ( a DC marker)
41
What do Natural killer dendritic cells (NK DCs) do?
- 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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