This document discusses innate lymphoid cells (ILCs) and natural killer (NK) cells. It covers their development, types and subsets. ILCs are lymphoid cells that lack antigen receptors but play a crucial role in innate immunity against microbes and stressed cells. NK cells are a subset of ILCs that can kill infected cells without further differentiation. The document outlines the activating and inhibitory receptors on NK cells that help them distinguish healthy from infected cells. It also discusses the clinical importance of NK cells and ILCs in diseases like rheumatoid arthritis and their potential as therapeutic targets.

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