L07 Flashcards
What is immunological tolerance
Mechanisms in place to ensure B and T cells do not respond to self
Regulation
Review of mechanisms of cellular interplay that ensures ?
Why do we need immunological tolerance?
random generation of repertoire of BCR and TCR and many self reactive specificities will be produced
- if no tolerance = autopathology
Give examples of a self Ag not expressed in thymus
Insulin, antibodies,
What is AIRE?
An autoimmune regulator protein that acts as a transcription factor
What does AIRE do?
Allows the expression of many tissue-specific-Ag (TSA) in the thymus
What do patients with AIRE deficiency/mutations end up with?
Major autoimmune syndrome
What makes T cells anergic?
When they come across APC without costimmulatory molecules, therefore no signal 2
What are other mechanisms of tolerance?
Immunological ignorance - Ag presented to T cells must be at a significant levels
Privileged sites - sites where immune cells do not go to (eyes, testis, CNS - there are barriers in place)
B cells are dependent on T cells for a response - which allows autoimmune B cells to exit BM
Treg.
What do Treg express?
FoxP3
What is FoxP3?
A transcription factor
What makes Treg a key player in regulating autoimmune B cells?
Expression of FoxP3 -> high affinity
What are types of Treg
natural Treg (nTreg), or induced Treg (iTreg)
What occurs when Treg is deficient?
Autoimmune syndrome
What cytokines are produced by Treg that inhibit other self-reactive T cells?
IL-10 and TGF-beta
What antigen is Treg specific for?
self antigen
Where are iTreg made?
Periphery
What is the regulatory B cell called?
Breg/10
What cytokine is produced by Breg?
IL-10
Why do we need regulation?
Ensure responses continue only for as long as they are needed
Reduce collateral tissue
Ensure ensure responses are qualitatively appropriate (right for the specific antigen)
What do T cell sub-sets have in relation to cytokine?
Cytokine secretion profile
What is the function of TH1 and what cytokine does it require?
Activate Mq, NK cells, CD8. IFN- gamma and IL-12
What is the function of TH2 and what cytokine does it require?
Promotes responses mediated by eosinophils, mast cells and plasma cells, Ab responses (IgE) IL-4.
What is the function of TH17 and what cytokine does it require?
Responses against fungi, IL-23, TGF-β, IL-6 and IL-1β
What is the function of Treg/Breg and what cytokine does it require?
Supress unwanted response - IL-10.
What is the function of TFH and what cytokine does it require?
Specialised Th found in GC to help B cells
How does TH1 activate Mq
secreting cytokines; IFN-gamma, GMCSF, TNF-alpha. By expressing CD40L which binds to CD40
What is the function of TFH and what cytokine does it require?
Secrete IL-17. Recruits neutrophils.
What is the other protein expressed by Treg?
CD25
What cytokines are secreted by Treg?
TGF-beta, IL-10
What does IL-10 do?
Inhibits APC function
Describe the polarisation of TH1 cytokines
promote commitment to TH1
inhibit development of TH2, TH17
Describe the polarisation of TH2 cytokines
promote commitment to TH2
inhibit development of TH1, TH17
Describe the polarisation of TH17 cytokines
promote commitment to TH17 cytokines
inhibit development of Treg
Describe the polarisation of Treg cytokines
inhibits Th1, Th2, Th17 responses
Explain the role of Treg in successful pregnancies
If there were no Treg’s the mother’s body would reject the baby, as its 50% father
What is the role of TGF-Beta
inhibition
