Why do we need immunological tolerance? - answer✔✔This allows us to get random generation
of the repertoire of BCR and TCR
This means self-reactive specificities will be made
Without tolerance, we will get self destruction
How do lymphocytes become tolerant? - answer✔✔Central tolerance - they encounter antigens
in the central lymphoid organs when they are immature
Peripheral tolerance - they encounter antigens in the peripheral tissues in the absence of other
necessary signals
What is the major tolerance? - answer✔✔Clonal deletion
The engagement of receptors on immature B cell or at cells lead to deletion
Which tolerance is more controlled? - answer✔✔T cell tolerance
B cells can escape selection
Why is T cell tolerance more controlled? - answer✔✔It can recognise self-MHC and
autoantibodies but this means it will be too good at recognition and can be killed
What are the 3 possible outcomes of random TCR gene rearrangement? - answer✔✔Failure to
recognise self-MHC (no survival signal)
Recognises self-MHC and peptide generates from self-antigen presented in thymus (removed by
negative selection as it binds too well)
Recognises self-MHC and any other peptide (expanded by positive selection)
Where is insulin expressed? - answer✔✔Beta cells in the pancreas
It can't be expressed in the thymus
What is AIRE? - answer✔✔autoimmune regulator protein
It is a transcription factor
Plays a role in tolerance induction
What does AIRE do? - answer✔✔It allows the expression of normal tissue-specific antigens in
the thymus and hence deletion of T cell that recognise these antigens
This leads to autoimmune syndrome
What is the outcome of AIRE is present? - answer✔✔The sucking can be expressed in our
thymus and it will remove auto reactive T cells - no T cells specific to insulin = diabetes
What is the outcome of AIRE is mutated? - answer✔✔The insulin won't be expressed in the
thymus; they will have lots of autoreactive T cells causing immunity problems
What does random Ig gene rearrangement lead to? - answer✔✔B cells expressing self-reactive
BCR
What is receptor editing? - answer✔✔B cells get a second chance to rearrange any self-reactive
BCR
They have further light chain gene rearrangement so that there is a possibility of expressing a
receptor that's not self-reactive
What happens to the immature T cells that fail the positive selection? - answer✔✔They undergo
further rearrangements of the TCR alpha locus to produce a different receptor
What genes rearrange the receptors? - answer✔✔RAG genes
What are anergic lymphocytes? - answer✔✔The unresponsive lymphocytes that recognise self-
antigens
How are immature B cells formed? - answer✔✔When receptors encounter antigens that is not
multivalent, this forms immature B cells which downregulate BCR
How do T cells become anergic? - answer✔✔They encounter antigens in the absence of co-
stimulation
How do B cells become anergic? - answer✔✔When the B cell get signal 1 without signal 2, they
become anergic
What are the other mechanisms of tolerance? - answer✔✔Immunological tolerance - many
antigens aren't presented at sufficient levels to activate T cells
What are regulatory T cells? - answer✔✔These are a T cell subset that suppressed the immune
response
How do Treg cells develop? - answer✔✔In the thymus from T cells with high affinity receptors
for self antigen (nTreg)
They can be induced in the periphery (iTreg)
What are nTreg? - answer✔✔Natural Treg cells
Generated in thymus
Self reactive
They control other self reactive cells that escape negative selection
What happens when there is a deficiency in Treg cells? - answer✔✔Leads to a severe
autoimmune syndrome IPEX
How is IPEX caused? - answer✔✔By mutations in the transcription factor which controls Treg
development - less Treg cells, more auto reactive cells harm us
What are iTreg cells? - answer✔✔This is when the nTreg cells produce cytokines in the
periphery which dampen down the effects of other T cells
They arise from circulating T cells in the peripheral tissue
What are regulatory B cells? - answer✔✔B10 makes IL10, dampening the immune system and
preventing autoimmunity
What happens after successful activation of the immune system? - answer✔✔CD4 T cells
differentiate into effector T cells
What are the different types of effector cells? - answer✔✔TH1 - activation of macrophages, NK
cells and cytotoxic T cells
TH2 - promotes responses mediated by eosinophils and mast cells, involved in IgE
TH17 - promote responses against fungi
Treg - suppresses unwanted response
Tfh - specialised T helper cells, produces TH1, TH2 and TH17 cytokines
What do TH1 and TH2 cells make? - answer✔✔TH1 cells make interferons which activate
macrophages
TH2 cells make IL4 but don't make macrophages
What is the link between TH1 cells and macrophages? - answer✔✔TH1 cells activate
macrophages;
- via secretion of cytokines
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