1) What is tolerance? What are the two types?
2) What is central tolerance?
3) What is peripheral tolerance? Give 2 reasons why it is needed?
4) What are Conditions that lead peripheral tolerance of foreign antigens (i.e. when does the
body know don’t produce a response against it)
5) What are some ways we deal with things it in peripheral tolerance? What are Privileged
sites? Give an example of this site.
6) How can you generate anergetic cell ( a form of peripheral tolerance)? Explain with an
example of a transgenic mouse with HEL self that is inject with antiHEL B cell.
7) If you have TGFb* AND IL10 what kind of CD4 T cells subsets are activated and what is
the result of this?
8) How are Treq cells produced in the thymus? Give the two explanamtion. What is their main
role? What are two location of producing T req.
9) How are the natural and induced Treq cells produced?
10) What are the four marker of Regulatory T cells (Treq)? what are the marker’s roles in the
11) Explain the direct contact and indirect method of inhibition of other T cell response by Treq
12) What is linked sepression?
13)CD8+ Tregs where are they produced? Mechanism of action?
14)What is autoimmunity? Autoreactive lymphocytes? Autoreactive disease? Given example of
15) If you have mutation in AIRE gene (APECED disease), FoxP3 ( IPEX disease) and Fas
receptor (CSS disease), what do you get?
16)Hashimotoo’s thryiditis: explain this autoimmune disease. What does it causes? What are
17)Insulin dependent diabetes mellitus (type 1): what is it caused by?
18)What is the animal model for IDDM.d
19) Myasthenia gravis: what is it caused by? Symptoms?
20) Rheumatoid arthritis: what causes it? Why is it called the systemic inflammatory disease?
How does it produce both Th1 and Th2 response?
21)Explain the pathways of the two response in RA and the cytokines or other factors that are
involved in it?
22)Systemic lupus erythematosus (SLE): what causes it? What are some symptoms? How can
you detect this disease?
23)MS: target? Symptoms? Genetic factors? Environmental factors?
24) Explain the mechanism of MS of damage in the brain.
25) Explain how the EAE model for MS in mouse works?
26)How do you know EAE mediated by T cell?
27)Explain what happen if Ag given orally to EAE mouse rather then injection? Explain using
28) Oral lead to active suppression (explain using experimental data)
29)How do Environmental factors favoring the development of autoimmune disease?
30) Explain how some can be genetically predisposed to autoimmune disease? Example?
31) Explain how infection can produce autoimmmunity?
32)Why do woman have more of these dieases?
33)What are some ways to treat autoimmunity? The best way is what? Lecture 10/11
1) The prevention of an immune response against selfstructures. We have Central and
2) When the lymphocyte gets exposed to self antigen and see if they react to it. Very strongly
reactive are killed before they leave the periphery.
3) It occurs after lymphocyte development. What happens outside the thymus like the oral
tolerance? 1) we have some escapes ( so it is like a backup mechanism). Often the cell might
see self antigens that it has not seen in the thymus but is still our or if we just don’t want to
react to it ( like the things in the gut).
4) Fetus if is exposed to an antigen when it come out it will be tolerant to it. Also if the antigen
is present to the t cell but an immature or inactive. There are other reasons as well such as no
costimulation, Longterm persistence of Ag means it is probably self ( in the gut this
happen), oral introduction,
5) Apoptosis, Anergy, T req and induce T req cells inhibit these cells and also Sequestration:
where you put it in a site where no other cell can see it. Also called privelaged sites. Eye is
privileged sites in our body. Damage to eyesà now the eye antigen is now carried to the
lymphà the body then generates a response against it and it is for both eyes not just one eyes .
6) Nocostimulation. If the mouse is transgenic for the HEL and it express as normal and natural
self antigen.à you take this and you inject an antiHEL naive B cell that will only bind HEL
antigen. This anti Hel naive B cell should be activated but it is not since the T cell will not
help it fight against what it considers as selfà no response ▯ turns ANERGIC. (no stimulation).
7) T req and it inhibits all the other subsets (Th1/2/3)
8) T req tend to work on selfreactive escapes T cells. T req produced when you have an
intermediate affinityà foxt3 is unregulatedà t req is produced. Or the other explanation to
which most people agree is that No interaction with MHC and the high affinity binding cell
( no apoptosis) might become the treq.
9) There are two ways we can produce the T req inside thymus that are called the natural or
outside thymus called the induced. Natural: produced as explained in above question.
Induced: exposed to (TGFb) in periphery.
10) CD4 : coreceptor for MHC Class II (CD8 Tregs also exist) . CD25 : IL2 receptor α chain
at high levels ( IL12. CTLA4 : binds to +: on APCs and delivers a negative signal to the T
cell (inhibits their response: #7) Foxp3 transcription factor ( #8)
11) Dependent: occur as Treg cells express high levels of inhibitory CTLA4 molecules.
Independent: rely upon secretion of cytokines (IL10, TGFβ, IL