Lecture-16 Natural Killer Cell and its anti-cancerous attributes pptx

Origin of NK cells among immune cells is made clear.
Inhibitory and activating signals of NK cells are highlighted.
KIRs distribution on NK cells and their gene complex are depicted. NK cell kills cancer cells deprived of MHC I- Missing self Hypothesis is indicated.

1. Lecture -16 Natural Killer Cell (NK Cell) Prof. Sreerama Krupanidhi Email: [email protected]

2. Focus 1) To appraise the developmental origin of NK cells 2) To acquaint with the function of NK cells 3) To familiar with activating and inhibitory KIR receptors and their gene complex 9/2/2024 Prof.Sreeraama Krupanidhi 2

3. Learning Outcomes Origin of NK cells among immune cells will be known. 2) Inhibitory and activating signals of NK cells will be known. 3) KIRs distribution on NK cells will be known. 4) NK cell kills cancer cells deprived of MHC I 9/2/2024 Prof.Sreeraama Krupanidhi 3

4. 9/2/2024 Prof.Sreeraama Krupanidhi 4

5. NK cell among Immune cells 9/2/2024 5 Prof.Sreeraama Krupanidhi

6. Nat u ral killer ( NK) c e lls a re large gr a nul a r l y m ph o cyt e s derived from common lymphoid progenitor cells. ( Lymphoblasts ). N K c e lls consti tu te 5 % -10% of total l y mp h o cyt e s i n h u ma n peripheral blood. N K c e lls are c y to t oxic; s m all gra n ules in their cytoplasm containing proteins such as perforins and proteases known as Granzymes , that will trigger either apoptosis or cell lysis in an abnormal cell. Defensins, an antimicrobial secreted by NK cells, directly kills bacteria by disrupting their cell walls. NK cells di f f er e nt i ate and ma t u r e i n t h y mu s , spl e en, b o n e marrow, lymph nodes and tonsils. NK Cells are embedded with KIRs both activating and inhibitory. NK cells identifies and targets the cancer cell lacking the class I MHC molecules/ depleting the class I MHC molecules. Biology of NK cell 9/2/2024 6 Prof.Sreeraama Krupanidhi

7. N K cells provide a n ear l y respo n s e to vir u s infection 9/2/2024 7 Prof.Sreeraama Krupanidhi

8. On the basis of the abundance of the CD56 glycoprotein on the cell surface and their cytotoxic potential, NK cells are divided into two subpopulations: CD56 dim NK cells: Comprises up to 90% of NK cells and is considered the most cytotoxic subset. It binds to the FC portion of IgG antibodies and mediate antibody dependent cell-mediated cytotoxicity (ADCC) of antibody-bound target cells. Expression of granzyme B and perforin is also high in this subset compared with CD56 bright NK cells (involved in abundant cytokine production and hence immunoregulatory function). 9/2/2024 8 N K cells: ‘ dim’ and ‘bright’ types Prof.Sreeraama Krupanidhi

9. NK cells kill cells that are infected with virus by blocking replication of virus. It maintains and even increase the inflammation in the infected tissue by secreting inflammatory cytokines such as interleukin (IL)-2, IL-12, IL-15 and interferon gamma. NK cells primarily kill tumor cells, they recognize cells that lack expression of major histocompatibility complex (MHC) class I antigens known as Missing Self Hypothesis. 9/2/2024 9 Functions Prof.Sreeraama Krupanidhi

10. Presence of Self-MHC molecule prevents killing NK cell function depends on the presence or absence of MHC I 9/2/2024 Prof.Sreeraama Krupanidhi 10

11. NK Cell- CD 56 Effector function Non- effector function NK cell Corpuscle with self MHC-I ligand Corpuscle with missing self MHC-I ligand iKIR aR a. No-lysis b. Target cell lysis aL MHC-I 9/2/2024 11 Prof.Sreeraama Krupanidhi

12. Pictorial representation of KIRs and the HLA Class I ligands to which they bind. Ligands for inhibitory KIR 2DL5, 3DL3 and activating KIRs are not known (or poorly defined). represents activating KIRs and represents inhibitory KIR . 9/2/2024 Prof.Sreeraama Krupanidhi 12

13. KIR genes and their names 9/2/2024 Prof.Sreeraama Krupanidhi 13 Symbol Name of the KIR genes KIR2DL1 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 1 KIR2DL2 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2 KIR2DL3 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 3 KIR2DL4 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 4 KIR2DL5A killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 5A KIR2DL5B killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 5B KIR2DS1 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 1 KIR2DS2 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 2 KIR2DS3 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 3 KIR2DS4 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 4 KIR2DS5 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 5 KIR2DP1 killer cell immunoglobulin-like receptor, two domains, pseudogene 1 KIR3DL1 killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 1 KIR3DL2 killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2 KIR3DL3 killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 3 KIR3DS1 killer cell immunoglobulin-like receptor, three domains, short cytoplasmic tail, 1

14. KIR gene complex 9/2/2024 Prof.Sreeraama Krupanidhi 14

15. NK cell function depends on the presence or absence of MHC I on the target cell Natural killer cell activation is determined by the balance of inhibitory and activating receptor stimulation. For example, if the inhibitory receptor signaling is more prominent, then NK cell activity will be inhibited; similarly, if the activating signal is dominant, then NK cell activation will start. 9/2/2024 Prof.Sreeraama Krupanidhi 15

16. Diseases caused by lack of NK cells Herpes simplex viruses (HSVs) inhibit the lytic activity of natural killer cells and interleukin 2- activated killer cells. Chediak -Higashi syndrome is an autosomal recessive disorder in which mutations in CHS1 gene, leads to the downregulation of immune response that includes neutrophils, macrophages, and NK cells. 9/2/2024 16 Prof.Sreeraama Krupanidhi

17. Summary NK cell originate from Hematopoietic stem cells through lymphoid progeny. Receptors namely KIRs on NK cells recognize MHC class I on the target cells. NK cells are antiviral and anti cancerous. Proportion of NK cells among immune cells is 5 to 10%. 9/2/2024 17 Prof.Sreeraama Krupanidhi

18. Study questions Elaborate on the origin, function and receptors of NK cells. Enlist KIRs and indicate their role 9/2/2024 18 Prof.Sreeraama Krupanidhi

19. Acknowledgements We acknowledge online resources/public domains for the use of the content to develop teaching material and to disseminate the knowledge. 9/2/2024 Prof.Sreeraama Krupanidhi 19

20. Thank you 9/2/2024 20 Prof. Sreerama Krupanidhi