Immunological Tolerance Flashcards
Give a definition of immunolgical tolerance
immunological tolerance occurs when an immunocompetent host fails to respond to a immunogenic challenge with a specific antigen
OR
Immunological tolerance occurs when an immunocompetent host fails to respond to the presence of a specific antigen.
What are the 2 immunological factors that are needed for toleranceof self?
Immunological non-responsiveness and ignorance
What the difference between the central and peripheral tolerance?
Central tolerance: this occurs during lymphocytes dev
Peripheral tolerance- occurs after lymphocyte leave the primary organs
What are the 4 steps of T-cell development?
Lineage commitment
TCR gene rearrangement Proliferation expansion Selection of useful and function repertoire
What is a positive selection and negative selection of thymocytes?
Positive selection- selection process of T-cells benficial to the host—> Equipped to make robust responses against foreign antigens
Negative selection- significant contributions to enforcing self-tolerance—> as positive selection goes on T-cells recognised antogen in association with self MHC. This selection is regulated by cortical epithelial cells in the thymus.—> However thymocytes that react strngly with self MHC are deleted (central tolerance)
What are the 3 types of strength interactions in the thymus microenvironment?
Low: T-cells dont bind to MHC will be useless for the host so they die from neglect
Appropriate: Cells are rescued: binding to MHC is not too weak or strong, cells are encouraged to survive and exit via the peripheral. (Positive selection)
High: Cells die by apoptosis: bind to strongly to self proteins, if released to the peripheral it would cause harm to the host (Negative selection)
Why in experiments male mice skin was rejected by female mice?
Males have a Y chromosome—>meaning different proteins produced—> female does not exhibit Y chromosome proteins so the female has never seen these proteins so the males skin is rejected
What is promiscious gene expression in the thymus?
THE THYMUS PRODUCES AND EXPRESSES ALL GENES AND PROTEINS IN THE BODY
What is AIRE and why is it important?
Autoimmune regulator is a transcription factor expressed in mTEC which permits promiscuous gene expression in the thymus
AIRE is important as the lack of it will develop autoimmunity, any T-cell that are tissue specific will mature and leave the thymus and cause autoimmunity.
What is the peripheral tolerance and why is it needed?
POTENTIAL MANY MORE PROTEINS WHICH ARE NOT EITHER EXPRESSED IN THYMUS OR SERUM, AND IN SOME CASES NOT EXPRESSED UNTIL AFTER THE IMUNE SYSTEM HAS MATURED
MECHANISM IS NEEDED WHICH PREVENTS AUTOREACTIVITY OF LYMPHOCYTES AFTER THEY HAVE EMIGRATED FROM THE THYMUS/BONE MARROW
What is anergy?
A state of immune unresponsiveness. Induced when the TCR is stimulated in the absence of a second signal from a APC (ANTIGEN PROCESSING CELL)
What are the 2 phenotypes of regulatory cells?
CD 25+, CD4+, need cell to cell contact in order to be an effective suppressor cell.
What is regulatory Tolerance?
Tcell specific for self antigens becomes regulatory T-cell
Cytokines produced by Treg inhibit othe self reactive T-cells
What is deletional tolerance?
Self reactive T-cells are deleted in the thymus but some might escape deletion, in the periphery such escaped T-CELLS CAN BE ACTIVATED
