Primary Immunodeficiencies Overview
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Questions and Answers

What is the primary defect seen in SCID with T-B-NK- phenotype?

  • Deficiency in gamma chain cytokine receptor
  • Deficiency in ADA enzyme (correct)
  • Impaired VDJ recombination
  • MHC II defect

    • What causes the hypogammaglobulinemia seen in Bruton’s X-linked agammaglobulinemia?

  • Defective T cell signaling
  • BTK signaling defect (correct)
  • Deficiency in somatic hypermutation
  • Mutations in CD40L

    • In DiGeorge Syndrome, what is the primary consequence of thymic aplasia?

  • Low levels of IgM
  • High levels of IgE
  • T cell deficiency (correct)
  • B cell deficiency

    • Which condition is characterized by a defect in the FoxP3 gene leading to a lack of peripheral tolerance?

    <p>IPEX syndrome</p> Signup and view all the answers

    What is the main immune defect in Chronic Granulomatous Disease (CGD)?

    <p>Defective phagocyte respiratory burst</p> Signup and view all the answers

    Which type of leukocyte adhesion deficiency results from a defect in CD18?

    <p>LAD1</p> Signup and view all the answers

    What is a common clinical symptom associated with Hyper IgM Syndrome due to CD40L mutation?

    <p>Increased susceptibility to bacterial infections</p> Signup and view all the answers

    Which syndrome results from a defect in both Fas and FasL leading to a failure of lymphocyte apoptosis?

    <p>ALPS</p> Signup and view all the answers

    How does the defect in MHC class II contribute to the symptoms of Bare Lymphocyte Syndrome type 2 (BLS-2)?

    <p>The defect in MHC class II results in low CD8+ T cells, leading to impaired T cell differentiation and T-dependent antibody responses.</p> Signup and view all the answers

    Describe the relationship between IgA deficiency and anaphylaxis associated with IVIg treatment.

    <p>IgA deficiency leads to low IgA levels while other immunoglobulin levels remain normal, which can trigger anaphylactic reactions during IVIg treatments.</p> Signup and view all the answers

    What are the clinical implications of a defect in the LYST gene seen in Chediak-Higashi syndrome?

    <p>Defects in the LYST gene lead to partial albinism, reduced NK and CD8+ cell function, and hemophagocytic lymphohistiocytosis.</p> Signup and view all the answers

    How does Job's syndrome result in increased susceptibility to infections?

    <p>Job's syndrome causes a defect in cytokine signaling, leading to high IgE levels and impaired immune responses against infections, particularly with cold abscesses.</p> Signup and view all the answers

    What challenges arise from the absence of Tregs in IPEX syndrome?

    <p>The absence of Tregs in IPEX syndrome leads to a lack of peripheral tolerance, resulting in autoimmune symptoms due to uncontrolled immune responses.</p> Signup and view all the answers

    Explain the main defect observed in Wiskott-Aldrich syndrome and its resultant symptoms.

    <p>Wiskott-Aldrich syndrome is caused by a defect in the WASP protein, leading to cytoskeletal issues in B and T cells, and symptoms include eczema, thrombocytopenia, and petechiae.</p> Signup and view all the answers

    What is the primary defect in Familial Hemophagocytic Lymphohistiocytosis and its effect on immune cells?

    <p>Familial Hemophagocytic Lymphohistiocytosis is caused by a perforin defect, which results in impaired cytotoxic function of NK and CD8+ T cells.</p> Signup and view all the answers

    Characterize the defects associated with the leukocyte adhesion deficiencies (LAD).

    <p>Leukocyte adhesion deficiencies result from defects in leukocyte extravasation, causing leukocytosis and a lack of pus formation during infections.</p> Signup and view all the answers

    Study Notes

    Primary Immunodeficiencies

    • Severe Combined Immunodeficiency (SCID)

      • SCID: Aspergillus and Candida, GI, respiratory infections - Broad range of infections affecting multiple organ systems.
      • SCIDXI: Common γ chain, cytokine receptor - A common molecular factor in the receptor system is deficient.
      • SCID defect T-B-NK-: ADA (purine salvage) - Adenosine deaminase deficiency prevents proper purine metabolism, leading to impaired immune function across multiple cell types.
      • SCID defect T-B-NK+: RAG (no VDJ recombination but NK cells are still fine) - RAG deficiency prevents the rearrangement of variable, diversity, and joining regions of genes in lymphocytes, impacting B and T cells but not NK cells.

    • Bare Lymphocyte Syndrome (BLS)

      • Pathophysiology: Defects in MHC I and II lead to impaired T-dependent humoral responses and T cell development.
      • BLS-1: MHC I defect (TAP transporter), low CD4+, bacterial upper respiratory infections - Defective transport of MHC I molecules leads to decreased CD4+ T-cells and elevated susceptibility to bacterial infections.
      • BLS-2: MHC II defect, low CD8+, - Defective MHC II molecules lead to decrease in CD8+ T-cells.

    • Hyper IgM Syndrome (HIGM)

      • HIGM1: CD40L, X-linked - Dysfunction in the CD40 ligand, an X-linked condition.
      • HIGM2: AID mutation (somatic hypermutation and class switching), hyperplastic GCs, AR - Somatic hypermutations and class switching are affected by AID mutations, leading to accumulations of proliferating germinal centers, an autosomal recessive disorder.
      • HIGM3: CD40, AR - Dysfunction in the CD40 receptor, an autosomal recessive condition.

    • Wiskott-Aldrich Syndrome (WAS)

      • WASP protein defect impacting cytoskeletal rearrangement in B and T cells, X-linked, eczema, thrombocytopenia, petechiae - A deficiency in WASP, an X-linked disorder, affects cytoskeletal structure affecting B and T cell functions leading to eczema, low platelets, and easy bruising.

    • DiGeorge Syndrome

      • 22q11, thymic aplasia, T cell deficiency (because of no thymus!) - A chromosomal deletion leads to thymic atrophy, impacting T cell formation and function.

    • Job's/Hyper IgE Syndrome

      • AD cytokine signaling defect from multiple sources, high IgE, cold abscesses, skeletal abnormalities, pneumatoceles (in lung) - Autoimmune disorders affect cytokine signaling mechanisms, leading to elevated IgE levels and various symptoms.

    • Bruton's X-linked Agammaglobulinemia (XLA)

      • BTK signaling, X-linked, B cell deficiency, pre- to pro-B cell defect - Disruption in B cell signaling pathways lead to decreased B cell development.

    • IgA Deficiency

      • Low IgA, other Igs normal. Mechanism unknown, anaphylactic to IVIg - Decreased levels of IgA, but other immunoglobulin types are normal, an unknown mechanism, and individuals are sensitive to intravenous immunoglobulin.

    • Chediak-Higashi Syndrome

      • Partial albinism, LYST gene, no vesicle transport or fusion, low NK, defective CD8+, and phagocytes, hemophagocytic lymphohistiocytosis - A LYST gene deficiency affects vesicle transport affecting NK cells , CD8+ and phagocytes. Can lead to excessive inflammation.

    • Familial Hemophagocytic Lymphohistiocytosis (FHL)

      • Perforin defect, NK and CD8+ defect - A deficiency in perforin leads to a defect in killing functions of NK and CD8+ lymphocytes.

    • IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, X-linked)

      • Fox3P gene, no Tregs, no peripheral tolerance - Decreased regulatory T-cells impact peripheral tolerance in immune response.

    • ALPS (Autoimmune Lymphoproliferative Syndrome)

      • Fas/FasL defect, no apoptosis in either tolerance, lymphadenopathy and hepatosplenomegaly (buildup of cells that need to be dead) - Apoptosis is affected by Fas/ FasL defects, leading to a buildup of immune cells and lymphadenopathy.

    • APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy)

      • AIRE deficiency, no central tolerance in cortical thymic epithelial cells - Deficient expression of AIRE impacts central tolerance in thymic epithelial cells.

    • Chronic Granulomatous Disease (CGD)

      • cp91PHOX, no respiratory burst from phagocytes, negative nitroblue tetrazolium, symptoms – infection from catalase+ organisms (because the respiratory burst is ROS), granulomas, and Aspergillus pneumonia - Impaired respiratory burst in phagocytes, leading to increased susceptibility to certain bacteria.

    • Leukocyte Adhesion Deficiencies (LAD)

      • Defect in leukocyte extravasation (leukocytosis, no pus when infected)
      • LAD1: CD18, low affinity integrin, no umbilical detachment - A deficiency in the CD18 protein leads to a low affinity integrin function causing delay in umbilical separation.
      • LAD2: selectin - Deficient selectins in leukocyte extravasation.
      • LAD3: high affinity integrin - Deficient high affinity integrins in leukocyte extravasation.

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    Description

    This quiz covers key aspects of primary immunodeficiencies, focusing on Severe Combined Immunodeficiency (SCID) and Bare Lymphocyte Syndrome (BLS). It explores various genetic defects and their impact on the immune system, including infection susceptibility and immune cell functionality. Test your knowledge on these critical immunological disorders.

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