USMLE® Step 1 style questions USMLE
A 2-year-old boy is brought to his primary pediatrician for evaluation of recurrent infections. The parents report the patient had two episodes of severe pneumonia, an episode of otitis media, and herpes labialis in the past nine months. He was born at 38 weeks gestation to a 28-year-old otherwise healthy woman. He eats and drinks normally and has achieved the normal developmental milestones. Vitals are within normal limits. Physical examination demonstrates a well-developed and well-nourished child with fair complexion. He has eczema on his cheeks and trunk as well as petechiae on the bilateral lower extremities. Laboratory evaluation reveals a leukocyte count of 8,000/mm3 and a platelet count of 70,000/mm3. Flow cytometry of peripheral lymphocytes reveal absence of the WAS protein. Which of the following immunologic processes is most likely affected given this patient's findings?
And there’s a problem with the immune system that leads to repeated infections.
All of the hematopoietic cells, which are cells in the bone marrow, produce Wiskott-Aldrich syndrome protein, or WASp for short.
There’s also a gene - called the WIPF1 gene, which encodes a protein called WAS/WASL-interacting protein family member 1, which helps stabilize Wiskott-Aldrich protein.
So WASp, aside from having a really long name that shortens down to the name of a scary flying insect - helps to reorganize the cell’s cytoskeleton, and therefore its overall shape.
The cytoskeleton can change by either adding to or removing actin proteins from the end of an actin chain.
The chain grows longer in the direction that a cell wants to move and shortens on the side that a cell wants to move away from.
This helps with various cellular activities like phagocytosis and cellular division.
Platelets specifically rely on this functionality, because they originate from large precursor cells called megakaryocytes.
The platelets then go off to form clots at damaged sites in the blood vessels, to stop bleeding.
When they encounter a pathogen, T-cells form pseudopods or false legs that reach out and synapse or communicate with other cells.
Think of it like they’re shaking hands to exchange information.
Next up are the cytotoxic T-cells and natural killer cells, which also reorganize their cytoskeleton to form an immunological synapse with various body cells to do surveillance, and find out if they’re healthy or if they’re infected or cancerous.
If an unhealthy cell is discovered, the immune cells make that unhealthy cell undergo apoptosis, or programmed cell death.
T-regs also rely on reorganizing their cytoskeleton to function normally. Finally, there are the phagocytic cells like monocytes, macrophages, and dendritic cells, which form small foot processes to make their way towards cytokines.
These cells also perform phagocytosis, to swallow up debris, dead cells, and bacteria, so that it can be processed and destroyed.
In Wiskott-Aldrich syndrome, a mutation in the gene results in a Wiskott-Aldrich protein that can’t function normally.
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