NK cell is an intriguing topic

1. ILC and NK cells
Ritasman Baisya

2. Points of discussion
• Introduction
• Development
• Types of ILC
• Subset of NK cell
• NK cell – activating and inhibitory receptors
• Mechanism of action
• Clinical importance

3. Introduction
• Innate lymphoid cells (ILCs) & Natural Killer (NK)
Cells - cells of lymphoid origin
• Morphology and functionally similar to T cell but
without T cell antigen receptor
• Crucial role in innate response against microbe and
stressed cell

4. DEVELOPMENT

5. Innate lymphoid cell
Types cytokines function
Group 1 ILCs ( like TH 1
cell )
IFN gamma Macrophage activation
Group 2 ILCs ( like TH2
cell )
IL-5, IL-9 and IL-13
Contribute to allergic
disease and
helminthic infection
Group 3 ILCs ( like Th17
cell)
IL 17, IL 22 ,GMCSF
Defence against
extracellular bacteria
maintaining the
integrity of epithelial
barriers

7. ILC - innate counterpart of T cell

8. NK cell
 Kill infected cells without any further differentiation after
development
 large, granular, bone marrow-derived lymphocytes - CD56+
CD3 - ( in humans ) .
 10% of peripheral blood total human lymphocytes - appear
as large lymphocytes with numerous cytoplasmic granules
 Also found in peritoneal cavity, spleen, liver, lung, lymph
nodes, thymus, and in uterus during gestation.
 Use germline DNA-encoded receptors to distinguish
pathogen-infected cells from healthy cells

9. Subset of Nk cell
CD 56 dim
• 90% of the total NK cell
population in peripheral
blood
• Functionally, these have
high cytotoxic activity
CD 56 bright
• 10 % of NK cell in blood is
CD 56 bright
• They produce cytokines

11. Receptors
• NK-cell function - controlled by a wide range of receptors
• Either activating or inhibitory in nature.
• NK cells distinguish infected and stressed cells from healthy
cells
• A particular NK cell typically expresses two to four inhibitory
receptors in addition to an array of activation receptors.
• There is sizeable heterogeneity within the NK-cell population.

12. NK cell receptor
Inhibitory receptor
• Killer immunoglobulin-like
receptors ( KIRs ) or Ig-like
receptors (CD158)
• C type lectin receptors
(CD94-NKG2A)
• leukocyte inhibitory
receptors (LIR1, LAIR-1).
Activating receptor
• Natural cytotoxicity
receptors ( NKp46, NKp44 )
• C type lectin receptors
(NKG2D, CD94 - NKG2C)
• CD16 (FcγRIII)

14. HOW RECEPTORS HELP IN NK CELL FUNCTION ?

16. Missing self recognition – a unique characteristics

17. Final pathway
• Perforin and granzymes mediated apoptosis
• A caspase-dependent apoptosis
• Antibody dependent cellular cytotoxicity (ADCC) - CD16.
• NK cell–derived IFN-γ increases the capacity of
macrophages to kill phagocytised bacteria

19. Role in rheumatic disease
• Killer-cell immunoglobulin-like receptors (KIRs) – role in
autoimmune diseases
• Most studies on KIRs have been based on the missing self
theory
• NK cells have either a disease-promoting or a disease-
controlling role.
• In RA tissue, NK cells has disease-promoting functions, by
tissue infiltration
• A disease-controlling role is clearly suggested in SLE patients

21. Take home message
• ILC – A new paradigm in immunology , is innate counterpart of adaptive
T cell response
• NK cells, much early discovered , can be considered as a subset of ILC
• NK cell and ILC - crucial role in stress response
• NK cell has activating and inhibitory receptors - helping its function
• KIR on NK cell - association in rheumatic disease
• role of NK cells in autoimmune diseases will help to define new
therapeutic targets.
• Emerging research on ILCs showing its both protective and promoting
role in autoimmunity

22. References
• Vivier E , Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer
cells. Nat Immunol. 2008 May ; 9(5) :503-10.
• Schleinitz N, Vély F, Harlé JR, Vivier E. Natural killer cells in human autoimmune
diseases. Immunology. 2010;131(4) : 451-8.
• Abul K. Abbas, Andrew H. Lichtman, Shiv Pillai, Cellular and Molecular
Immunology , eighth edition.
• Olshid Sanati, Zahra Aryan, Mehri Barbadi & Nima Rezaei (2015) Innate lymphoid
cells are pivotal actors in allergic, inflammatory and autoimmune diseases, Expert
Review of Clinical Immunology, 11:8, 885-895,

23. thank you