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Printable Handouts
Navigable Slide Index
- Introduction
- Overview of lecture - introduction
- Leukocytes – the challenge
- Leukocyte recognition
- Immunoreceptors
- Immunoreceptor (NTR) signalling module
- Immunoreceptor signalling
- Examples of immunoreceptors
- Association of NTRs with shared adaptor subunits
- Overview of lecture - immunoreceptor triggering
- Immunoreceptor triggering: the example of the TCR
- Phosphorylation of TCR ITAMs is dynamically regulated
- Size of TCR vs. other cell surface molecules
- Kinetic-segregation model of TCR triggering
- Verified predictions of the model
- Distribution of CD45 and TCR
- Most NTRs are triggered by this kinetic-segregation model
- NTRs tested use the KS mechanism
- Other immunoreceptor (NTR) triggering mechanisms
- Alternate NTR triggering mechanisms: Induce proximity/aggregation
- Role of TCR 'coreceptors'
- Mechanisms of coreceptor function
- Alternate NTR triggering mechanisms: conformational change
- Conformation change in the cytoplasmic domains
- Overview of lecture - signal integration between immunoreceptors
- Signal integration in leukocyte recognition
- Immunoreceptor signalling motifs
- Types of signalling integration
- Inhibitory immunoreceptors in immune recognition
- NK cells detect changes in the ratio of inhibitory vs. activatory ligands
- Immunoreceptor receptor/ligand complexes span a similar distance
- Optimal inhibition of activatory requires matched size of ligands
- Similar receptor/ligand dimensions enables colocalization and signal integration
- Optimal inhibition requires matched sizes and colocalization
- Membrane-proximal signal integration
- Signal integration between TCR and costimulatory receptors
- TCR and some CD28 signals integrate in the nucleus
- Key ideas
- Overview of lecture – paired immunoreceptors
- Paired activatory and inhibitory immunoreceptors
- Most immunoreceptor families have paired receptors
- Activatory and inhibitory receptor pairs
- Conclusions
- Acknowledgments
Topics Covered
- Introduction to immunoreceptors
- Immunoreceptor signalling
- Immunoreceptor triggering
- Signal integration between immunoreceptors
- Paired immunoreceptors
Links
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Talk Citation
van der Merwe, A. (2020, November 30). Immunoreceptors [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 8, 2024, from https://doi.org/10.69645/ITKP1626.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Anton van der Merwe has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: The Immune System - Key Concepts and Questions
Transcript
Please wait while the transcript is being prepared...
0:00
Hello. I'm Anton van der Merwe from the University of Oxford,
and I'm going to be talking about immunoreceptors.
0:09
This is an overview of my talk,
starting with an introduction.
0:14
The challenge that leukocytes face is that they are the only cells
that we have that throughout their lifetime migrate throughout the body,
making contact with a very large variety of cells.
What they are doing is trying to discriminate between the normal cells,
which are the vast majority and the occasional abnormal cell
and then selectively target their response to abnormal cells.
Now another challenge is that what they're trying to detect
are the presence of infecting microorganisms or cancer,
and these are highly variable and rapidly evolving.
0:46
The process of leukocyte recognition which has to tackle
this problem is mediated primarily by leukocytes cell surface receptors.
These bind to soluble or surface associated ligands.
The ligands include self molecules,
as well as molecules derived from pathogens.
There are over 300 receptors found on leukocytes in many different families.
A typical leukocyte may express 100 or more receptors,
and the single largest group of these receptors are termed immunoreceptors.
1:18
Immunoreceptors are also called non-catalytic
tyrosine-phosphorylated receptors or NTRs for reasons which will become clear.
They largely confine to leukocytes,
so they've evolved essentially for leukocyte recognition.
They have very diverse and rapidly evolving ectodomains,
but their cytoplasmic domains are relatively
conserved and link up to conserved signaling pathways.
What these pathways are characterized by are that they have tyrosine- containing motifs
which are phosphorylated by Src-family tyrosine kinases or SFKs.
This phosphorylation is regulated by receptor protein tyrosine phosphatases,
which are restricted to leukocytes.