NK cells Flashcards
LO
- Explain the basic biology of NK cell biology; identifying key receptors important for NK function
- Identify the role of NK cells in an immune response and how viruses and cancer attempt to evade them
- Describe how NK cells may be part of the adaptive immune system and how they interact with adaptive immune cells
NK cell lecture topics
- What are NK cells?
- Activation of NK cells
- Recognition of infected/cancer cells
- Diversity in NK cells
- CMV and NK cells – evolution and co-evolution
What is the break down of the immune system, tell me the sub-divisions of each and what is included into each.
Where do NK cells fit into this?
Innate
- Humoral- complement, haptoglobin
- Cellular- granulocytes, NK cells
Adaptive
- Humoral- antibodies, B cells
- Cellular- T cells
Linkers
- Humoral- cytokines, chemokines
- Cellular- dendritic cells
Draw a graph with titre on the y-axis and time on the x-axis and draw on the lines of:
adaptive immune response
innate immune response
virus titre
Tell me about the evolution of NK cells
- NK cells evolved much earlier than other lymphocytes
- Fundamental role in the immune system
- First described in 1975
- Kiessling et al Eur J Imm
What is the innate immune system cell lineage, where do NK cells come into this lineage?
What types of cells are NK cells, how do they exist in the blood?
- lymphocytes
- cytotoxic, small granular cells
- contains small granules in their cytoplasm which contain proteins such as perforin and proteases known as granzymes
- monomorphic lineage
What are some of the roles that NK cells have in the body?
Anti-viral response
- Herpes group of viruses (CMV, VZV, HSV, EBV)
- Bacterial infections?
Emerging role in anti-tumour response
Interface with adaptive immune system
How can NK cells be identified?
- Use flow cytometry to distinguish cell types
- Flow cytometry is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles and looking at the cell’s markers also
- NK cells are CD3- / CD56+
Tell me the function of NK cells, what are the main three?
NK cells are important in anti-viral activity and can shape the adaptive immune response
1) Primary role is to kill target cells
2) Proliferate to generate more NK cells to kill target cells
3) Recruit other immune cells
In which two ways do cytokines stimulate NK cells following activation
- Cytotoxicity
- Proliferation
What cytokines are involved in NK cell cytotoxicity?
Cytotoxicity = IFN-alpha, IL-2, IL-12 and IL-15
What cytokines are involved in NK cell proliferation?
Proliferation = IFN-gamma, IL-12, IL-15, IL-18, and IL-21
How do cytokines work in order to stimulate NK cells following activation?
Synergistically
NK cells secrete cytokines following activation,
What cytokines are released, especially in the following circumstances…
- Th1 cell activation
- Th2 cell activation
IFN-gamma, TNFalpha and GM-CSF – Activation of Th1 cells
IL-4 and IL-10 – Activation of Th2 cells
MIP-1beta
What are the three main ways in which NK cells kill?
What types of interactions are involved in each?
Antibody dependent cellular cytotoxicity (ADCC)
- FcgRIII interaction (receptor on cell surface)
Natural cytotoxicity
- Receptor-ligand interaction
Apoptosis of infected cell
- Fas-Fas ligand/TRAIL-DR4
What are the steps to antibody depdendent cellular cytotoxicity of NK cells?
- Antibodies bind to cell surface
- NK cells bind to antibody - mediated by CD16 (FcgRIII)
- NK cell secretes perforin – induces lysis of target cell
- Target cell death
- NK cell secretes cytokines and chemokines which activate other immune cells
How does natural cytotoxicity of NK cells occur?
Receptor/Ligand interaction between proteins on NK and target cell surface
Induces activation leading to release of cytotoxic granules (perforin/granzyme)
However, NK cells do not just have an activating interaction, they also have inhibitory receptors. There is a balance between these two receptors.
What are the different inhibitory and activating receptors of the NK cell?
Tell me the types of receptors NK cells express and when certain ones may be expressed?
T cells and B cells only express one receptor, TCR and BCR respectively
Co-activating ligands are only expressed on stressed or infected cells
How are NK cells activated?
Balance between activating and inhibitory receptors
Natural cytotoxicity receptors (these bind multiple ligands)
What are some of the natural cytotoxic receptors that can activate NK cells?
Natural cytotoxicity receptors (these bind multiple ligands)
- NKp30
- NKp44
- NKp46 (binds influenza haemagglutinin- only binds to this ligand when infected with influenza virus)