Natural Killer Cells

Question 1

Describe natural killer cells.

Answer 1

-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

Question 2

Describe the role of NK cells in innate immunity.

Answer 2

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

Question 3

Describe a normal cell VS abnormal cell.

Answer 3

-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

Question 4

How do NK cells recognize abnormal cells?

Answer 4

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

Question 5

Describe NK cell receptor differences in species.

Answer 5

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)

Question 6

Describe KIRs.

Answer 6

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

Question 7

Describe KLRs.

Answer 7

-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

Question 8

Describe activating receptors on NK cells.

Answer 8

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

Question 9

Describe inhibitory receptors on NK cells.

Answer 9

-CD94/NKG2A KNOW THIS

Question 10

Describe NK cell cytotoxicity mechanisms.

Answer 10

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

Question 11

Describe perforin-dependent mechanism.

Answer 11

-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

Question 12

Describe CD95 mechanism.

Answer 12

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

Question 13

Describe CD16 killing pathway (ADCC).

Answer 13

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

Question 14

Describe the regulation of NK cell activity.

Answer 14

-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

Question 15

Describe NK T cells (NKT).

Answer 15

-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

Question 16

Describe NK dendritic cells (NK DCs).

Answer 16

-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