Download Autoimmunity

Biol 430
Question Bank
Autoimmune Diseases
1. Determine if each of the following statements is true (T) or false (F). If it is false, explain why.
a. ____ A ‘cryptic antigen’ would be best described as an autoimmune self-antigen that has not yet
been identified.
b.____ Through the process of intermolecular epitope spreading, a B-cell specific for one epitope
can potentially activate a T-Cell with a TCR for a different epitope.
c. ____ ‘Molecular mimicry’ results from infections by two closely related bacterial species.
d.____ The similarity between SLE and a Type-III hypersensitivity-like mechanism is that both
involve: deposition of immune complexes in tissues or on vessel walls.
e. ____ Immune privileged sites would be best described as areas of the body that are most
commonly afflicted with autoimmune disorders.
f. ____ “Stimulating antibodies”, such as those of Grave’s Disease, trigger apoptosis in the target
cell.
g.____ The autoimmune disorder called myasthenia gravis is caused by antibodies against the
acetylcholine receptor.
h.____ The etiology of multiple sclerosis involves antibodies that block the function of synapses.
2. Match each of the following autoimmune disorders with the correct description.
Disorder
Description
a. ___ multiple sclerosis
A. cell-mediated attack of beta cells of pancreas
b. ___ rheumatoid arthritis B. antibodies against RBCs causes anemia.
c. ___ SLE
C. involves cell mediated and humoral attack of myelin sheath
d. ___ myasthenia gravis
D. antibodies cause excessive production of thyroid hormones
e. ___ Type I diabetes
E. immune complex deposition is widespread in body
f. ___ Graves disease
F. involves autoimmune attack of neuromuscular junction
G. Presence of anti-IgG antibodies is common
3. Describe three different mechanisms by which a viral infection can contribute to the onset of a
autoimmune disease. If the virus were to produce a superantigen, how might this lead to an
autoimmune response?
Biol 430
Question Bank
Autoimmune Diseases
Page 1
4. Indicate if each of the following mutations is likely to cause (+) autoimmunity or not (-), and if so,
whether the cause would be failure of central (C) or peripheral (P) tolerance. (‘—’ means loss of
function ‘++’ means over-expression.
+ / -C/P
++
A. MHC
____
____
—
B. CD4
____
____
—
C. AIRE
____
____
—
D. FasL
____
____
++
E. INFγ
____
____
—
F. TLR9
____
____
—
G. FoxP3
____
____
H. C3
____
____
5. The process called “epitope spreading” offers an explanation
of how B-cells and T-cells can become activated against selfantigens. The diagram to the right shows a segment of DNA
bound to a gene regulatory protein (possessing three alphahelix domains – 1, 2, & 3).
Explain how a B-cell with a surface receptor specific for an
epitope in domain 1 could potentially present to and activate a
T-cell with a TCR for an epitope in domain 2.
6. It is believed that a variety of pathogens can contribute to auto immune diseases through molecular
mimicry. For example, infections by the Epstein-Barr virus (EBV) have been associated with multiple
sclerosis (MS).
A. Many people are subject to infections by EBV but a relatively small percentage of these
develop an autoimmune disease. Why?
B. Mis-recognition of antigens more commonly involves the cell-mediated than the humoral arm
of the adaptive immune system. Explain how this might be explained by the differences in
antigen recognition by antibodies and TCRs.
C. The figure below shows a structural similarity between EBV protein and human myelin basic
protein, a protein known to be a target of autoimmunity in multiple sclerosis. What other types
of evidence would you like to see before accepting that this amino acid sequence from EBV
causes MS?
Biol 430
Question Bank
Autoimmune Diseases
Page 2
7. Azab et al. examined the roles of Treg cells in patients with SLE. The study group consisted of 20
females and 4 males ranging in age from 16 to 45 years old. The status of their disease was assessed
using the SLE Disease Activity Index (SLEDAI), which defines SLE activity according to 24 clinical
and laboratory parameters. SLEDAI scores ranged from 4 to 40; oddly enough, lower scores indicate
more severe activity of the disease. FACS analysis was used to quantify numbers of CD4+CD25+ and
CD4+CD25+High cells, the latter possessing higher levels of membrane CD25.
A. Why might the study group involve more females than males? Is this a flaw in the
experimental design?
B. What are some of the characteristics might you expect to be included in the SLEDAI?
C. Why is there an interest in cells with the CD4+CD25+ phenotype?
CD4+CD25+ and CD4+CD25+High cells were distinguished on the bases of the Mean Fluorescence
Index (MFI, i.e. the intensity of
fluorescence) of CD25 on the cells;
CD4+CD25+high cells represented the top
2% of CD4+T cells with the brightest
CD25 expression.
D. In the figures to the right show
where you would expect
CD4+CD25+ and CD4+CD25+High
cells to be found in a FACS
analysis.
In the analysis shown to the right, the percent of CD4+ cells
that were CD25+, and the MFI of CD25 in CD4+CD25+High
cells, were compared to the SLEDAI for each person.
E. What property of the cells does the MFI measure?
F. How might these results relate to the severity of the
disease symptoms?
Azab N, Bassyouni I, Emad Y, Abd El-Wahab G, Hamdy G, Mashahit M.
2008. CD4+CD25+ regulatory Tcells (T REG) in Systemic Lupus
Erythematosus (SLE) patients: The possible influence of treatment with
corticosteroids. Clinical Immunology 127: 151–157.
Biol 430
Question Bank
Autoimmune Diseases
Page 3