Immune Tolerance Flashcards
What are the three things your immune system could do wrong?
Auto-immunity
Allergy
Hypercytokinemia and sepsis ( too much response )
What is the three signal model?
Antigen recognition
Co-stimulation
Cytokine release
All three signals required to allow a response
What are the three possible outcomes of immune response?
- Resolution : no tissue damage, phagocytosis of debris
- Repair : healing and scar tissue, fibroblast and collagen synthesis
- Chronic inflammation : attempts to repair ongoing damage
What are the two types of Tolerance?
Central Tolerance : Before Lymphocytes enter circulation
Peripheral Tolerance : Once in circulation
What is Peripheral Tolerance?
Destroy or control any self reactive lymphocytes which do enter circulation
- or B cells that can change
What Changes occurring in B cells after antigen exposure can cause auto-immunity issues?
Although BCR is made in bone marrow before B cells are released
A process called Affinity Maturation occurs after antibody production that can cause changes
How can a T cell become anergic?
If a naive T cells sees a MHC/peptide without a co-stimulatory signal is is unresponsive and will be less likely to be stimulated in the future by that peptide
How can a T cell response be classified as ‘ignorant’?
Antigen in too low concentrations to reach the threshold for receptor triggering
What is antigen induced cell death?
Activation through T cell receptor can result in apoptosis
Often caused by the induction of expression of the death ligand, Fas ligand ( CD95 ligand, FasL )
What is Central tolerance?
Destroy self-reactive Lymphocytes before they enter circulation as part of their maturation in the generative organs
B cell selection in central tolerance?
If immature B cell in bone marrow encounters an antigen in a form which can cross-link their IgM - apoptosis is triggered
T cell selection in central tolerance?
In the thymus:
- If T cell is useless ( doesn’t bind to any self MHC at all) = apoptosis
- If T cell is dangerous ( binds to MHC too strongly ) = negative selection apoptosis
- If T cell is useful ( Binds to MHC weakly ) = positive selection and signal to survive
How can a T cell developing in the thymus encounter MHC bearing peptides?
A specialised transcription factor allows thymic expression of genes hat are expressed in peripheral tissues otherwise
AIRE ( autoimmune regulator ) promoted self tolerance by allowing thymic expression of genes from other tissues
What do mutations in AIRE result in?
Multi-organ autoimmunity :
autoimmune polyendocrinopathy syndrome type 1
What to T regulatory cells do?
They are a subset of helper T cells
Inhibit other T cells and other cells ( DCs, macrophages, etc)
