mechanisms of tolerance Flashcards
What is the immune system tolerant to
Tolerant to self,
the immune system is tolerant to harmless antigens such as food or environmental ag
the immune system is tolerant to commensal microbiota
How do T-cells recognise antigens
They recognise self MHC I/II,
1 for CD8 and 2 for CD4
How do B-cells recognise antigens
They recognise all antigens, non-self antigens in any form and will elicit a response.
What is immunological equilibrium
The balance between lymphocyte activation and control, one side has activation in response to pathogens and the other side is tolerance, so there is no response to self and other harmless antigens
How is self-tolerance induced
It is induced in central lymphoid organs and is then maintained in the periphery
How is the diversity of B and T cells repertoire brought about
random somatic gene rearrangement, the mechanism is common to B and T-cells
Outline T-cell self-tolerance induction
generation of TCR repertoire requires many random mechanisms to allow diversity, the specificity of TCR in the immature repertoire will include cells that are harmful (negatively selected), useless (neglected) and useful (positively selected)
What cells complete maturation
Only cells that have antigen receptor with an appropriate affinity for the peptide presented in self MHC complexes complete their maturation and form the peripheral T-cell pool
What is peripheral tolerance
Its main purpose is to ensure that self-reactive T and B cells that escaped central tolerance do not cause autoimmune disease.
How are B-cells activated
They are activated via T-cells but auto-reactive B cells can be present without being able to be activated if there is no help available.
What is tolerance
if help is provided (e.g. injection of autoantigen coupled to immunogenic foreign carrier) B-cells will carry out an immune response.
What are the different mechanisms of peripheral tolerance
ignorance: lymphocytes fail to recognise or respond, immunologically privileged sites (eyes, testis etc).
clonal anergy: binding of the antigen makes lymphocyte unresponsive
suppression: interaction with cytokines to inhibit lymphocyte responsiveness
clonal exhaustion: continues stim by persistent antigen may wear out responsive cells
How does clonal anergy work
To have a full activation of naive T-cell you need antigen recognition but also secondary costimulation (CD28) and so to inhibit the response CTLA-4 must be presented instead which causes those T-cells to become anergic.
