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CMB2004 COMPLETE EXAM QUESTIONS AND ANSWERS
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CMB2004 COMPLETE EXAM QUESTIONS ANDANSWERS
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 cells or at cells leads 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 generated 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 cells 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, it becomes 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 Treg cells are deficient? - 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, produce 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
- CD40L binding to macrophage CD40
What happens when macrophages are activated by TH1 cells? - ANSWER It
increases the microbicidal activity of macrophages
This increases the fusion of phagosomes with lysosomes
This increases the synthesis of oxygen radicals, NO and proteases
What do TH17 cells do? - ANSWER Secrete IL17 and recruit neutrophils early in
infections
What are CD4 Treg cells? - ANSWER They are a kid or CD4+CD25+ cells and
CD8+ cells
They secrete suppressive cytokines - TGF beta and IL10 (inhibits APC function)
What are the 3 signals delivered to T cells? - ANSWER Signal 1 - activation
Signal 2 - survival
Signal 3 - differentiation
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