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Questions and Answers
Which of the following cellular processes is NOT directly affected by the impaired WASP protein in Wiskott-Aldrich syndrome?
Which of the following cellular processes is NOT directly affected by the impaired WASP protein in Wiskott-Aldrich syndrome?
- Cytoskeletal rearrangement during platelet formation.
- Migration of phagocytic cells towards cytokine gradients.
- Formation of pseudopods by T cells for immunological synapse.
- Differentiation of megakaryocytes into erythrocytes. (correct)
How does the Th2-skewed response in Wiskott-Aldrich Syndrome contribute to the development of eczema?
How does the Th2-skewed response in Wiskott-Aldrich Syndrome contribute to the development of eczema?
- By enhancing IgM levels, improving the skin's defense against infections.
- By increasing Th1 cell activity, leading to a stronger immune response against pathogens.
- By suppressing IgE production, reducing allergic inflammation.
- By promoting IgE production and eosinophilic inflammation, exacerbating allergic reactions. (correct)
In Wiskott-Aldrich syndrome, how does the impaired function of invariant natural killer T (iNKT) cells contribute to the increased risk of autoimmunity and cancer?
In Wiskott-Aldrich syndrome, how does the impaired function of invariant natural killer T (iNKT) cells contribute to the increased risk of autoimmunity and cancer?
- By increasing the production of regulatory T cells, preventing autoimmunity.
- By promoting T cell activation and reducing the threshold for autoimmune responses.
- By enhancing the surveillance and elimination of cancerous or infected cells.
- By failing to effectively regulate B cell responses, leading to increased self-antibody production. (correct)
Why might Wiskott-Aldrich syndrome be underreported or misdiagnosed?
Why might Wiskott-Aldrich syndrome be underreported or misdiagnosed?
How does WASP deficiency affect B cell homeostasis in Wiskott-Aldrich syndrome?
How does WASP deficiency affect B cell homeostasis in Wiskott-Aldrich syndrome?
In the context of X-linked inheritance, why are males almost exclusively affected by Wiskott-Aldrich syndrome?
In the context of X-linked inheritance, why are males almost exclusively affected by Wiskott-Aldrich syndrome?
What is the primary function of the WASP protein in hematopoietic cells, and how do mutations in the WAS gene disrupt this function leading to Wiskott-Aldrich syndrome?
What is the primary function of the WASP protein in hematopoietic cells, and how do mutations in the WAS gene disrupt this function leading to Wiskott-Aldrich syndrome?
How does microthrombocytopenia in Wiskott-Aldrich syndrome contribute to an increased risk of bleeding?
How does microthrombocytopenia in Wiskott-Aldrich syndrome contribute to an increased risk of bleeding?
What aspect of megakaryocyte function is impaired in Wiskott-Aldrich syndrome due to the defective WASP, leading to thrombocytopenia?
What aspect of megakaryocyte function is impaired in Wiskott-Aldrich syndrome due to the defective WASP, leading to thrombocytopenia?
A research study aims to investigate the efficacy of gene therapy in treating Wiskott-Aldrich syndrome. What primary outcome measure would be the MOST indicative of successful immune reconstitution?
A research study aims to investigate the efficacy of gene therapy in treating Wiskott-Aldrich syndrome. What primary outcome measure would be the MOST indicative of successful immune reconstitution?
Flashcards
Wiskott-Aldrich Syndrome (WAS)
Wiskott-Aldrich Syndrome (WAS)
A rare, X-linked disorder characterized by immunodeficiency, thrombocytopenia, and eczema.
Etiology of WAS
Etiology of WAS
Mutations in the WAS gene, affecting cellular signaling and immunological synapse formation.
Epidemiology of WAS
Epidemiology of WAS
Rare, X-linked disorder primarily affecting males, with an estimated incidence of 1 in 100,000 live births.
Pathogenesis of WAS
Pathogenesis of WAS
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T cell function in WAS
T cell function in WAS
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B cell function in WAS
B cell function in WAS
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NK T cells in WAS
NK T cells in WAS
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Thrombocytopenia in WAS
Thrombocytopenia in WAS
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Eczema in WAS
Eczema in WAS
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Immunodeficiency in WAS
Immunodeficiency in WAS
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Study Notes
Wiskott-Aldrich Syndrome (WAS) Overview
- WAS is a rare X-linked disorder characterized by a triad of immunodeficiency, thrombocytopenia, and eczema.
- Mutations in the WAS gene cause WAS, affecting cellular signaling and immunological synapse formation.
- The condition is seen almost exclusively in males, with an estimated incidence of 1 in every 100,000 live births.
- WAS may be underreported due to misdiagnosis.
Etiology of Wiskott-Aldrich Syndrome
- Mutations in the WAS gene, located on the X chromosome, cause WAS.
- The WAS gene encodes the Wiskott-Aldrich syndrome protein (WASP), essential for hematopoietic cell function and immune response.
- WASP is critical for cellular signaling and immunological synapse formation between immune cells.
- Mutations disrupt the ability of T cells to communicate effectively, impairing the immune response.
Epidemiology of Wiskott-Aldrich Syndrome
- WAS is rare, with an estimated incidence of 1 in every 100,000 live births.
- It is primarily seen in males due to its X-linked recessive inheritance pattern.
- There is no ethnic or geographical predominance, but the syndrome is underreported due to misdiagnosis.
Pathogenesis of Wiskott-Aldrich Syndrome
- Mutations in the WAS gene result in an impaired WASP protein, vital for cytoskeletal rearrangement.
- Cytoskeletal rearrangement is crucial for the function of T cells, B cells, and platelets.
- Impaired WASP affects immunological synapse formation and cellular signaling.
Immunological Synapse Formation and Cellular Signaling
- T cells rely on pseudopods to interact with other cells, but in WAS, their ability to form these is impaired, affecting migration, adhesion, and interaction with B cells.
- B cell homeostasis is disrupted, leading to the depletion of circulating mature B cells and compromising the humoral immune response.
- Invariant natural killer (NK) T cells are completely absent in WAS patients, increasing susceptibility to autoimmunity and cancer.
Cytoskeletal Disruption in Platelets
- Platelets are formed from megakaryocytes, and WAS disrupts this process due to defective WASP.
- Defective WASP results in fewer and smaller platelets (microthrombocytopenia), increasing the risk of bleeding.
Phagocytosis and Immune Function
- Phagocytic cells rely on cytoskeletal rearrangement to move toward cytokines and carry out phagocytosis.
- In WAS, these cells are impaired in their ability to move and engulf foreign invaders.
Clinical Presentation of Wiskott-Aldrich Syndrome
- Eczema: Dry, red patches of skin, often becoming infected due to immune system dysregulation and impaired skin barrier function.
- Eczema in WAS is caused by:
- T-cell dysfunction leading to poor immune regulation and chronic inflammation.
- Th2-skewed response causing high IgE and allergic inflammation.
- B-cell dysfunction resulting in low IgM and immune imbalance.
- A weakened skin barrier increasing allergen penetration.
- Poor neutrophil/macrophage function, leading to recurrent skin infections.
- Eczema in WAS is caused by:
- Thrombocytopenia: Low platelet count leading to easy bruising, prolonged bleeding times, and an increased risk of bleeding.
- Immunodeficiency: Increased susceptibility to bacterial, viral, and fungal infections due to impaired immune cell function.
Genetics of Wiskott-Aldrich Syndrome
- WAS is inherited in an X-linked recessive manner, primarily affecting males.
- Females are usually carriers but can sometimes show mild symptoms.
- X-linked Thrombocytopenia: A milder form caused by smaller mutations in the WAS gene, mainly leading to thrombocytopenia.
- Wiskott-Aldrich Syndrome Type II: Caused by mutations in the WIPF1 gene, which stabilizes WASP, with similar symptoms to classic WAS.
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