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Printable Handouts
Navigable Slide Index
- Introduction
- Aim of the lecture
- A simple view of an immune response
- Naive CD4 T cells differentiation
- Achieving tolerance to self antigens
- Central tolerance
- Peripheral self antigen expression in the thymus
- Aire KO mice develop autoimmune pathology
- Peripheral tolerance to self antigens
- Peripheral deletion
- Aire expressing cells play a role in deleting autoreactive T cells
- eTAC can induce tolerance through deletion
- LEC can induce tolerance through deletion
- Blockade of PD-L1 rescues FH cells from deletion
- CD8+ DCs and cross presentation
- Cross presentation model
- Reduced proliferation of OVA-reactive CD8+ T cells
- Transferring OT1 cells into an animal results in initial proliferation followed by cell death
- Clonal anergy
- In vivo significance of anergy
- Sequestration, immune privilege, ignorance
- Ignorance
- The autoreactive cells are there, but don’t do anything unless provoked
- Regulation of the immune response
- Expression of Foxp3 in the thymus and periphery
- Prevention of IBD and autoimmune gastritis
- Adult mice depend upon Foxp3+ T cells for tolerance and survival
- Autoimmunity induced following use of checkpoint blockade for cancer therapy
- Tolerance and autoimmunity
- T cells that recognise self antigen can be detected in the peripheral blood
- Not all self antigens are expressed in the thymus
- Iodination of thyroglobulin
- Hormonogenic sites in human thyroglobulin
- Tolerance and autoimmunity
- Induction of autoimmune thyroid disease
- Thyroiditis scoring system
- Induction of other diseases
- Factors that promote tolerance
- Experimental examples of tolerance protocols
- Aerosol peptide prevents EAE
- Induced tolerance was transferrable by Treg cells
- Tolerance and autoimmunity
- Thank you
Topics Covered
- Central and peripheral mechanisms involved in tolerance
- Aire as an important transcriptional regulator
- The importance of regulatory T cells
- The role of inhibitory molecules
- Factors than can promote tolerance
Links
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Talk Citation
Cooke, A. (2020, October 29). Tolerance and autoimmunity [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/MFPW5936.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Emerita Anne Cooke 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 everybody. I'm Anne Cooke.
I'm the Emeritus Professor of Immunobiology in
the Pathology Department in the University of Cambridge.
Today I'm going to talk about immune tolerance and autoimmunity.
0:14
Now, the aim of this lecture is really to understand
how self-tolerance is established and maintained,
and how it might be broken, and obviously,
if it's broken, it has the possibility of leading to autoimmune diseases.
0:28
Now, a very simplistic view of an immune response is that antigen enters the system,
is taken up and presented by a dendritic cell and
presented to a helper T-cell in the context of MHC class II.
The helper T-cell can provide help for a cytotoxic T-cell or to a B-cell,
and the B-cell can elaborate antibodies.
It also has been activated by antigen as a cytotoxic T-cell.
Now, once the antigen is clear from the immune system,
then everything returns back to baseline to homeostasis,
and the immune response itself dies down, but of course,
you will have some memory responses almost certainly generated during that time.
1:08
The type of T-cell that a naive T-cell differentiates into
is dependent on the cytokines that are around at the time of the initial stimulation.
For example, in the context of IL-12 being produced by dendritic cells,
you will get a predominantly Th1 response.
That response is very effective at dealing with viruses and bacteria,
and is important for intracellular immunity in the context of how far you get Th2 cells,
and Th2 cells can help B-cells and they're really important
in dealing with extracellular large pathogens, for example, helminths.
IL-6 together with TGF-beta is involved in
the generation of Th17 cells which are important to mucosal immunity
and TGF-beta alone in the absence of inflammatory cytokines can
lead to the development in the periphery of regulatory T-cells which are host protective.