The Wiskott-Aldrich Syndrome: An X-linked Primary Immunodeficiency - PowerPoint PPT Presentation

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The Wiskott-Aldrich Syndrome: An X-linked Primary Immunodeficiency

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The Wiskott-Aldrich Syndrome: An X-linked Primary Immunodeficiency Kristin Goff WAS Primary immune deficiency disorder Entails part of the bodies immune system is ... – PowerPoint PPT presentation

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Title: The Wiskott-Aldrich Syndrome: An X-linked Primary Immunodeficiency


1
The Wiskott-Aldrich SyndromeAn X-linked Primary
Immunodeficiency
  • Kristin Goff

2
WAS
  • Primary immune deficiency disorder
  • Entails part of the bodies immune system is
    missing or does not function properly
  • Caused by genetic defects in the immune system
  • X-linked recessive trait
  • Genetic defect causing deficiency is on the
    X-chromosome
  • Only affects males and is passed to child from
    the mother, a healthy carrier of the disorder

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Symptoms
  • Thrombocytopenia (low platelet count and
    disturbed platelet function)
  • Recurrent infections
  • Eczema
  • Malignancies in the form of leukemia and lymphoma
    occur in more severe cases

6
Normal platelets
7
Small Platelets
8
History
  • First described by German physician Alfred
    Wiskott in 1937
  • Robert Anderson Aldrich described the disease as
    an X-linked recessive trait in 1954
  • Joined the list of Primary Immune Deficiency
    Diseases in the 1960s

9
Mutations
  • WAS is associated with the absence of the
    Wiskott-Aldrich Syndrome protein (WASP) which is
    caused by simple mutations in the WASP gene
  • Missense and frameshift mutations are two known
    to cause WAS

10
A missense mutation has the ability to change
one amino acid into a different amino acid,
altering the protein and possibly causing it to
be nonfunctional.
A frameshift mutation deletes a DNA base,
shifting the entire sequence and changing the
amino acids from that point on. In this case,
the Mutation turns an amino acid in the protein
sequence into a stop codon and translation of
the protein is prematurely ended.
11
Actin Reorganization
  • WASP is involved in the reorganization of the
    actin skeleton. When the WAS protein is altered,
    it does not properly bind and actin
    reorganization is prohibited.

12
Affect on T Lymphocytes
  • Cytoskeleton reorganization is involved in the
    binding of T lymphocytes to antigen-presenting
    cells through CD3 crosslinking.
  • Without actin reorganization, CD3 is not properly
    presented at the cells surface and the T cell is
    not activated.
  • Causes recurrent viral and fungal infections (as
    noted in symptoms).

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Affect on B Lymphocytes
  • Thymus dependent B lymphocytes need T cells for
    activation and differentiation.
  • B cells only able to produce IgM through thymus
    independent B lymphocytes.
  • Causes recurrent bacterial infections because
    proper antibodies are not produced against
    certain bacteria.

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Treatment
  • Intravenous immunoglobulin substitution
  • Specialized antibiotics
  • Splenectomy
  • Hematopoietic stem cell transplantation

18
WAS Discovered in Females
  • Skewed X-chromosome inactivation in a female
    carrier can cause the typically healthy female to
    exhibit clinical signs of the disorder.
  • Causes the X-chromosome carrying the normal WASP
    gene to become inactivated so only the
    X-chromosome with the mutant WASP gene is left
    active.

19
Summary
  • WAS is caused by a mutation in the WASP gene.
  • A mutation in the WASP gene inhibits actin
    reorganization.
  • Without actin reorganization, CD3 cannot be
    presented and T cells are not activated.
  • Thymus dependent B cells are not activated
    without production of T cells.
  • B cell differentiation does not occur and only
    IgM antibodies are produced.
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