Exam 1: Natural Killer Cells

Question 1

Characteristics of NK cells

Answer 1

Kill virus infected cells, tumor cells, stressed cells, parasitic worms

Use different types of receptors to recognize targets

Recognize and attack target cells that express certain stress associated molecules

Question 2

Where are NK cells located

Answer 2

Bone marrow, peripheral blood, spleen, lymph nodes

Question 3

What are NK cells the first line of defense against

Answer 3

Pathogens like viruses

Question 4

Origin of NK cells

Answer 4

Lymphocytes –> Innate lymphoid cells (ILC) –> NK cells

Bone marrow –> hematopoietic stem cell –> common lymphoid progenitor –> NK/T cell precursor –> NK cell

Question 5

What triggers activation of NK cells - way 1

Answer 5

When target cells fail to express MHC class I molecules

This causes NK cells to lose their inhibition about attacking such cells

Question 6

NK cell receptors (4)

Answer 6

1. Killer cell Immunoglobulin (Ig)-like receptor (KIR or CD158)
2. Ly49 Receptor
3. NKG2 receptor
4. Fc receptor (CD16) –> for antibodies

Question 7

How do NK cell receptors act

Answer 7

1. KIR binds to MHC (target cell) = Inhibition
2. Ly49 binds to MHC (target cell) = Inhibition

3.NKG2 binds to altered MHC (target stressed cell) = Activation
Altered MHC = MICA or MICB

4. Fc binds to Ab on target cell = Activation

Question 8

Species differences between MHC class I receptors on NK cells

Answer 8

Humans - possess single, non functional Ly49 gene, so rely on KIR molecules

Mice rely totally on Ly49 molecules

Horse - Ly49

Bovine, cat, dog, pig - mainly KIR, some Ly49

Question 9

3 major receptors on NK cells

Answer 9

Ly49

NKG2

CD16 (Fc)

Question 10

Ly49

Answer 10

Recognizes MHC class I molecules and suppress NK cytotoxicity

In other mammals Ly49 may be replaced by KIR

Question 11

NKG2

Answer 11

Receptor for molecules such as MICA and MICB - commonly expressed on stressed, virus infected, or tumor cells

Question 12

CD16 (Fc)

Answer 12

Binds immunoglobulins and triggers target cells death by antibody-dependent cytotoxicity

Question 13

IFN-y

Answer 13

Potent stimulant of both NK cells and macrophages

Question 14

NK cell functions (9)

Answer 14

1. Destruction of tumor cells
2. ADCC against tumor cells
3. GVH disease
4. Reproduction functions
5. Control of hematopoiesis
6. Destruction of virus infected cells
7. Destruction of bacteria and fungi
8. Autoimmunity graft rejection
9. Destruction of parasites

Question 15

Do NK cells develop memory

Answer 15

NK cells are always on

NK cells may develop memory to some antigens for several months

Question 16

Natural Killer T Cells (NKT)

Answer 16

Share properties with both NK and T cells

Serve as bridge between innate and adaptive immunity

Question 17

Mode of action of NKT cells

Answer 17

Use CD1d as an antigen presenting molecule

Question 18

Recognition of target cells

Answer 18

1. Healthy normal cells express MHC I which inhibits NK cell activity
2. If cells express altered MHC I, no inhibitory signal activated –> NK cells kill it

Question 19

What triggers activation of NK cells - way 2

Answer 19

Activated by expression of stress related proteins on target cells