Case Study: Wiskott-Aldrich Syndrome

Before you read the case or begin answering the following questions RECALL what you have
learned in previous courses about the cellular cytoskeleton. Some terms that might come to
mind include actin, talin, microtubules, intermediate filaments

1. Per the case, what types of effector cells do T cells interact with?
T cells interact with B cells, dendritic cells and infected cells that are targeted through the
initiation of cell-cell contact via receptors. (Case Study)
2. What results when helper T cells interact with B cells? (list 4 effects, as stated in the
case)
a. Stimulate B-cell proliferation
b. Stimulate B-cell differentiation
c. Stimulate B cell isotype switching
d. Stimulate the generation of memory cells
(Case Study)
3. T cells kill infected target cells. What happens within the T cell to cause the secretion of
products?
The T cell reorganizes its cortical actin cytoskeleton which then results in the secretion of
products to the target cell. Specifically, T cells that kill virus infected cells come in direct
contact with the infected cells. The cytoskeleton itself, is linked to cell-surface receptors
on the T cell so if the T cell comes into contact with certain antigens, it will elicit the
response of reorganizing its cytoskeleton. The T cell will reorganize it’s cortical actin
cytoskeleton locally at the zone of which contact is made. This will result in a
microtubule-dependent mechanism to where it secretes cytokines and other products
towards the target cell. (Case Study)
4. Which of Jonathan’s lab results were abnormal?
Hemoglobin, platelet count & size, positive DAT, decreased IgM levels, increased IgA
and IgE levels, lack of Antibodies in reverse typing, low antibody titers of previous
vaccinations, lack of expression of Wiskot-Aldrich syndrome protein in lymphs via flow
cytometry (Case Study)
5. What specific protein was found to be absent in Jonathan’s lymphocytes?
Wiskot-Aldrich syndrome protein was found to be absent (Case Study)
6. What disorder developed after Jonathan’s bone marrow transplant?
Acute graft versus host disease was developed after marrow transplant (Case Study)
7. Explain why Jonathan’s blood type changed. (use your deductive reasoning)
Red blood cells are made in the bone marrow via hematopoiesis, since Jonathan received
bone marrow from a donor that was B positive, the donor’s bone marrow, specifically

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 new donor hematopoetic stem cells produced red cells that expressed a different blood
type than Jonathan’s original. (Case Study, prior knowledge, textbook)
8. Using your answer to #2, explain why Jonathan didn’t respond to the pneumococcal
vaccine.
Vaccines function to provide an antigen that will elicit an immune response and generate
memory to provide immunity if the antigen comes into contact with the body again;
however, this immunity cannot be acquired if the main cells that produce humoral
immunity are affected. Due to the inability for Jonathan’s T cells to secrete cytokines on
B cells, this did not allow B cells to differentiate into Plasma Cells. Additionally,
immunoglobulin isotype switching was also impaired and deficient along with generation
of memory cells. Furthermore, individuals with WAS have a decreased ability to form
antibodies against carbohydrate antigens such as blood group antigens and the anti-
pneumococcal vaccine. (Prior Knowledge, Textbook)
9. List the S&S of Wiskott-Aldrich Syndrome
Abnormally small platelets
Thrombocytopenia
Bleeding in bowel movements
Eczema
Petechiae
Autoimmunity/autoimmune disorders
Antibody deficiencies
Reduction of marginal zone in spleen
Susceptibility to pyogenic bacterial and opportunistic infections
(Case Study)

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