Biol 430QuestionBank Autoimmune Diseases

1. Determine if each of the following statements is true (T) or false (F). If it is false, explain why.

  1. ____ A ‘cryptic antigen’ would be best described as an autoimmune self-antigen that has not yet been identified.
  1. ____ 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.
  1. ____ ‘Molecular mimicry’ results from infections by two closely related bacterial species.
  1. ____ 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.
  1. ____ Immune privileged sites would be best described as areas of the body that are most commonly afflicted with autoimmune disorders.
  1. ____ “Stimulating antibodies”, such as those of Grave’s Disease, trigger apoptosis in the target cell.
  1. ____ The autoimmune disorder called myasthenia gravis is caused by antibodies against the acetylcholine receptor.
  1. ____The etiology of multiple sclerosis involvesantibodies that block the function of synapses.

2. Match each of the following autoimmune disorders with the correct description.

DisorderDescription

a. ___ multiple sclerosisA. cell-mediated attack of beta cells of pancreas

b. ___ rheumatoid arthritisB. antibodies against RBCs causes anemia.

c. ___ SLEC. involves cell mediated and humoral attack of myelin sheath

d. ___ myasthenia gravisD. antibodies cause excessive production of thyroid hormones

e. ___ Type I diabetesE. immune complex deposition is widespread in body

f. ___ Graves diseaseF. 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?

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 self-antigens. The diagram to the right shows a segment of DNA bound to a gene regulatory protein (possessing three alpha- helix 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).

  1. Many people are subject to infections by EBV but a relatively small percentage of these develop an autoimmune disease. Why?
  2. 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.
  3. 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?


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 assessedusing the SLE Disease Activity Index (SLEDAI), which definesSLE 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+Highcells, the latter possessing higher levels of membrane CD25.

  1. Why might the study group involve more females than males? Is this a flaw in the experimental design?
  2. What are some of the characteristics might you expect to be included in the SLEDAI?
  3. Why is there an interest in cells with the CD4+CD25+ phenotype?

CD4+CD25+ and CD4+CD25+Highcellswere distinguished on the bases of the Mean Fluorescence Index (MFI, i.e. the intensity of fluorescence) of CD25 on the cells; CD4+CD25+highcells represented the top 2% of CD4+T cells with the brightest CD25 expression.

  1. In the figures to the right show where you would expect CD4+CD25+ and CD4+CD25+Highcells 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+Highcells, were compared to the SLEDAI for each person.

  1. What property of the cells does the MFI measure?
  2. 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 (TREG) in Systemic Lupus Erythematosus (SLE) patients: The possible influence of treatment with corticosteroids. Clinical Immunology 127: 151–157.

Biol 430Question BankAutoimmune Diseases

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