Natural Killer Cells Flashcards

1
Q

Describe natural killer cells.

A

-originate in bone marrow
-found in blood, spleen, liver
-migrate to diff tissue via chemotatic, cytokine, & adhesion receptors during inflammatory response = activated
-dont have receptors made through gene segment rearrangement
-‘lg granular lymphocyte’
-lytic granules kill infected/tumor cells

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2
Q

Describe the role of NK cells in innate immunity.

A
  1. Kill virus infected, tumor, stressed cells
    -activation in vitro via cytokines like IL2 & IFNy = become lymphokine activated killer cells (LAK) *NOT FOUND IN VIVO (BODY)
  2. Cytokine & chemokine production: IFNy & TNFs & IL
    -activates macrophages
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3
Q

Describe a normal cell VS abnormal cell.

A

-normal cell surface markers present = express self MHC I
-abnormal cells dont express MHC I
>express MHC I chain related A (MICA & MICB), rae1, H60

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4
Q

How do NK cells recognize abnormal cells?

A

2 types of recog receptors:
1. Activating = kill abnormals
2. Inhibitory = dont kill normals
*activating signals blocked by inhibitory signs to prevent killing of normal cells

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5
Q

Describe NK cell receptor differences in species.

A
  1. Immunoglobulin like receptors
    -humans, cattle, dog, cat, pig
    -NK cell receptor recog MHC I = killer cell immunoglobulin-like receptor (KIRs)
  2. Lectin like receptors
    -mice, rats, horses
    -NK cell receptors recog MHC I = killer cell lectin like receptors (KLRs)
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6
Q

Describe KIRs.

A

-type 1 transmembrane proteins
-polymorphic
-includes leukocyte immunoglobulin like receptors (LILRs) = expressed on NK cells & leukocytes
-KIRs expressed on NK cells & lymphocytes

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7
Q

Describe KLRs.

A

-NKG2D receptor = expressed on activate T cells
-recognizes stress proteins like MICA, MICB
>high expression of stress proteins allows binding of NKG2D by overriding inhibitory signals through MHC I & permits NK cell cytotoxicity

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8
Q

Describe activating receptors on NK cells.

A

-bind to ligands expressed on abnormal cells
-NKG2D, CD16, NKp46 KNOW THIS

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9
Q

Describe inhibitory receptors on NK cells.

A

-CD94/NKG2A KNOW THIS

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10
Q

Describe NK cell cytotoxicity mechanisms.

A
  1. perforin-dependent
  2. CD95
  3. CD16 (ADCC)
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11
Q

Describe perforin-dependent mechanism.

A

-NK cell releases perforin
-perforin creates perforin channels on target cell
-granulysin, NK lysin, & fragmenetin = released from cytotoxic granules & go thru perforin channels
-granzymes & protease induce apoptosis of target cell

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12
Q

Describe CD95 mechanism.

A

-NK cells express CD95L
-target cells have CD95
-bind CD95L (NK cells) to CD95 (target cell) = apoptosis

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13
Q

Describe CD16 killing pathway (ADCC).

A

-NK cells recognize target cells = antibody dependent pathway using CD16
-CD16 = Fc receptor on NK cells
> NK cell cytotoxicity

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14
Q

Describe the regulation of NK cell activity.

A

-NK cells activated by cytokines (IL1, IL2, IL12, IL15, IL18, IL21, type I & II IFNs
-NK cells + cytokines = lymphokine activated killer cells (LAK) increased cytotoxic capacity used for cancer/tumors
-some viruses inhibit NK cell cytotoxicity

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15
Q

Describe NK T cells (NKT).

A

-similar to NK & T lymphocytes
-thymic origin
-1% of peripheral blood mononuclear
-express invariant a/B TCR
-express NK1.1 & KLR receptors
-CD4+ cells or may be double negative
-recognize glycolipid antigens on bacteria
-activated by IL15
-no memory cells
-link T cells to NK cells
-allergies, antitumor immunity, autoimmunity, & antimicrobial immunity

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16
Q

Describe NK dendritic cells (NK DCs).

A

-share properties with NK cells
-express NK1.1 = NK cell marker
-express CD11c = DC marker
-present in spleen, liver, lymph nodes, & thymus
-LYSE TUMOR CELLS
-present antigen to naive T cells (APC)
-link innate & adaptive