Primary Immunodeficiencies and Innate Immunity Deficiencies
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Primary Immunodeficiencies and Innate Immunity Deficiencies

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Questions and Answers

What is a primary consequence of MHC Class II deficiency in patients?

  • Reduced antigen presentation to mature helper T cells (correct)
  • Increased maturation of helper T cells
  • Enhanced humoral and cell-mediated immune responses
  • Improved response to viral infections

    • Which of the following is NOT a characteristic feature of Wiskott-Aldrich Syndrome?

  • Abnormal platelet sizes and shapes
  • Impaired actin cytoskeleton stabilization
  • Deficiency in Class II MHC gene expression (correct)
  • Recurrent infections

    • What type of genetic defect is associated with Wiskott-Aldrich Syndrome?

  • Malfunction in CIITA gene regulation
  • Dysfunction in RFXAP protein synthesis
  • Mutation in WASp protein (correct)
  • Defect in Class II MHC transcription factors

    • What immunological impact does MHC Class II deficiency have on patients?

    <p>Decreased helper T cell maturation</p> Signup and view all the answers

    Which of the following symptoms is typical for patients with Bare Lymphocyte Syndrome, Type II?

    <p>Skin granulomatous lesions</p> Signup and view all the answers

    What characterizes severe congenital neutropenia?

    <p>Neutrophil counts lower than 0.5 x 10^9 neutrophils/liter</p> Signup and view all the answers

    What is a common presentation associated with cyclic neutropenia?

    <p>Frequent episodes of severe periodontal disease</p> Signup and view all the answers

    What is the consequence of a defect in NADPH oxidase in chronic granulomatous disease?

    <p>Reduced production of reactive oxygen species</p> Signup and view all the answers

    What is the consequence of a deficiency in IL7Rα?

    <p>Lower antibody levels</p> Signup and view all the answers

    What condition arises from the loss of the common γ subunit?

    <p>X-linked SCID</p> Signup and view all the answers

    What is a frequent treatment for severe congenital neutropenia?

    <p>Aggressive antibiotic therapy and G-CSF</p> Signup and view all the answers

    What is not a characteristic of chronic granulomatous disease?

    <p>Neutrophil counts within normal range</p> Signup and view all the answers

    In cyclic neutropenia, what is the main cause of fluctuating neutrophil counts?

    <p>Apoptosis of developing neutrophils</p> Signup and view all the answers

    What is the primary cause of primary immunodeficiencies?

    <p>Inherited genetic mutations</p> Signup and view all the answers

    Which of the following is NOT typically associated with primary immunodeficiencies?

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

    What type of infection are patients with C3 deficiency particularly susceptible to?

    <p>Gram-negative bacterial infections</p> Signup and view all the answers

    What is the main consequence of Complement C1s deficiency?

    <p>Impaired immune complex clearance</p> Signup and view all the answers

    Which immunodeficiency is characterized by high white blood cell counts and recurrent skin infections?

    <p>Leukocyte Adhesion Deficiency (LAD)</p> Signup and view all the answers

    Which population is most affected by genetic mutations that cause primary immunodeficiencies?

    <p>Males with one X chromosome</p> Signup and view all the answers

    What is the effect of Factor H deficiency in the complement system?

    <p>Excess complement activation and inflammation</p> Signup and view all the answers

    Which of the following is an example of a secondary immunodeficiency?

    <p>Acquired Immune Deficiency Syndrome (AIDS)</p> Signup and view all the answers

    What can result from the C7 deficiency in the complement system?

    <p>Impaired formation of the Membrane Attack Complex (MAC)</p> Signup and view all the answers

    Which characteristic often indicates an underlying immunodeficiency?

    <p>Frequent infections</p> Signup and view all the answers

    Which condition is characterized by asthma, eczema, and increased susceptibility to viral infections?

    <p>Wiskott-Aldrich Syndrome</p> Signup and view all the answers

    What is a key factor that influences the success of stem cell transplant in Wiskott-Aldrich Syndrome?

    <p>Age of the child at transplant</p> Signup and view all the answers

    In DiGeorge Syndrome, what is one consequence of the genetic defect?

    <p>Underdeveloped thymus</p> Signup and view all the answers

    How is X-linked agammaglobulinemia primarily identified?

    <p>Lack of B cells and serum antibodies</p> Signup and view all the answers

    What is a common symptom associated with antibody deficiencies, such as selective IgA deficiency?

    <p>Asymptomatic presentation in many cases</p> Signup and view all the answers

    What kind of infections are individuals with X-linked agammaglobulinemia particularly susceptible to?

    <p>Extracellular bacterial infections</p> Signup and view all the answers

    What is a potential treatment option for DiGeorge Syndrome?

    <p>Thymic transplantation</p> Signup and view all the answers

    What genetic change is associated with DiGeorge Syndrome?

    <p>Deletion of a portion of chromosome 22</p> Signup and view all the answers

    What is a common symptom associated with deficiencies in an IgG subclass?

    <p>Frequent upper respiratory tract infections</p> Signup and view all the answers

    Which condition is characterized by an inability to bind B cells and no class switching?

    <p>CD40L Hyper IgM syndrome</p> Signup and view all the answers

    What is a consequence of AID deficiency?

    <p>Normal to high concentrations of IgM and low IgG</p> Signup and view all the answers

    In which demographic is common variable immunodeficiency (CVID) most frequently diagnosed?

    <p>Around 2 years of age or in 20s and 30s</p> Signup and view all the answers

    Which mutation is NOT commonly associated with common variable immunodeficiency (CVID)?

    <p>CD40L</p> Signup and view all the answers

    What is the primary treatment method for antibody deficiencies such as CVID?

    <p>IVIG or SCIG infusions</p> Signup and view all the answers

    What is the hallmark laboratory finding in patients with common variable immunodeficiency (CVID)?

    <p>Very low serum levels of at least two Ig isotypes</p> Signup and view all the answers

    Which of the following infections are patients with AID deficiency particularly susceptible to?

    <p>Bacterial respiratory and GI infections</p> Signup and view all the answers

    Why do patients with CD40L Hyper IgM syndrome have lower cell-mediated immunity?

    <p>They cannot produce IL-12</p> Signup and view all the answers

    In patients with CVID, the lack of antibody response may affect how they respond to what?

    <p>Infections and vaccinations</p> Signup and view all the answers

    Study Notes

    Primary Immunodeficiencies

    • Primary immunodeficiencies are caused by inherited genetic mutations
    • Over 100 primary immunodeficiencies have been described
    • These deficiencies affect immune cell development and/or function
    • Primary immunodeficiencies are characterized by recurrent and sometimes overwhelming infections
    • Most cases are genetically inherited as recessive traits
    • Often, the gene responsible for the deficiency is located on the X chromosome, leading to higher rates of disease in males

    Innate Immunity Deficiencies

    • Complement Deficiencies:
      • C1s deficiency: Leads to impaired classical complement pathway activation, resulting in reduced IgM/IgG complement activation and impaired clearance of immune complexes.
      • C2 Deficiency: Disrupts both classical and mannose pathways, increasing susceptibility to bacterial infections, even from normally non-pathogenic organisms.
      • C3 Deficiency: Patients produce no detectable C3, resulting in susceptibility to a wide array of bacterial infections, particularly gram-negative bacteria, leading to recurrent sepsis, pneumonia, and wound infections.
      • C7 Deficiency: Prevents the formation of the Membrane Attack Complex (MAC), which is important for killing bacterial pathogens.
      • Factor H deficiency: Leads to increased C3 and C5 convertase activity, resulting in excessive complement activation and increased inflammation, potentially causing glomerulonephritis and renal failure.
      • Defects in other complement components also result in recurrent infections by extracellular bacteria, which require opsonization for control.
    • Leukocyte Adhesion Deficiencies (LADs):
      • Deficiency in CD18 or β2 chain of LFA proteins, causing impaired adhesion of immune cells to endothelial cells and poor extravasation.
      • Patients experience high white blood cell counts (WBCs) and recurrent infections, often in the skin, with little or no pus formation.
      • Characterized by delayed umbilical stump separation due to inflammation at the site.
    • Neutropenia:
      • Characterized by lower than normal neutrophil counts.
      • Severe congenital neutropenia: Causes consistent low neutrophil counts (below 0.5 x 109 neutrophils/liter), leading to frequent bacterial infections and requiring aggressive antibiotic therapy and granulocyte colony-stimulating factor (G-CSF) treatment.
      • Cyclic neutropenia or elastase deficiency: Caused by a mutation in the gene encoding neutrophil elastase, resulting in decreased enzyme activity and leading to apoptosis of developing neutrophils. Fluctuating neutrophil counts contribute to periods of high infectious risk, along with frequent severe periodontal disease.
    • Chronic Granulomatous Disease (CGD):
      • Characterized by the inability to produce reactive oxygen species (ROS) in phagocytes.
      • Leads to recurrent bacterial infections, often in the lungs and skin.
      • Caused by defects in NADPH oxidase (Phox), with the X-linked form (gp91phox) being the most common.

    T and B Cell Immunodeficiencies

    • Common γ Subunit of Cytokine Receptors:
      • IL7Rα deficiency: In mice, IL7Rα is critical for T cell and B cell development, with some humans experiencing lower antibody levels.
      • X-linked SCID (Severe Combined Immunodeficiency): Loss of the γ subunit disrupts cytokine receptor signaling, affecting critical cytokines crucial for T and B cell maturation and function. Patients experience bacterial respiratory infections, bronchiectasis, and skin granulomatous lesions.
    • MHC Class II Deficiency (Bare Lymphocyte Syndrome, Type II):
      • Caused by mutations in transcription factors regulating class II MHC gene expression, such as CIITA, RFX5, RFXAP, and RFXANK.
      • Transcription of class II MHC genes is inhibited, leading to reduced helper T cell maturation and impaired antigen presentation to developing helper T cells.
      • Patients present with severe, recurrent infections due to disrupted humoral and cell-mediated immunity.
    • Wiskott-Aldrich Syndrome (WAS):
      • Genetic defect in WASp (Wiskott-Aldrich syndrome protein), expressed by hematopoietic stem cells to stabilize the actin cytoskeleton, leading to abnormal size, shape, and functions of cells such as platelets and lymphocytes.
      • Clinical presentations: Asthma, eczema, allergic diseases, increased susceptibility to viral infections, and increased susceptibility to encapsulated bacterial infections.
      • Treatment: Stem cell transplantation before age 5, depending on the child’s overall health, match between donor and recipient, and age.
    • DiGeorge Syndrome:
      • Genetic defect resulting in an underdeveloped thymus, caused by a deletion in a portion of chromosome 22.
      • Affects multiple body systems, leading to very low T cell numbers and varying phenotypes based on the size of the deletion.
      • Treatment: Thymic transplantation, non-transplant options like management of cardiac abnormalities and prevention of opportunistic infections, with prognosis varying based on disease severity and treatment.

    Antibody Deficiencies

    • X-linked agammaglobulinemia:
      • Characterized by recurrent bacterial infections (Streptococcus pyogenes, Staphylococcus aureus), chronic viral infections (poliovirus, Hepatitis B and C), and typically detected months to a year after birth.
      • Caused by a mutation in Bruton’s tyrosine kinase (BTK), a kinase important in signal transduction from the pre-B cell receptor. BTK mutations prevent pre-B cell receptor signaling, leading to apoptosis and resulting in a lack of B cells and serum antibodies.
    • Selective IgA Deficiency:
      • Many cases are asymptomatic. Symptomatic cases often involve deficiency in at least one IgG subclass.
      • Symptoms vary, including frequent upper respiratory tract infections caused by bacteria, GI infections (often with Giardia), and increased risk for asthma, eczema, celiac disease, and ulcerative colitis.
    • CD40L Hyper IgM Syndrome:
      • Characterized by a lack of CD40L expression on activated T cells, preventing interaction with CD40 on antigen-presenting cells (B cells, dendritic cells), leading to an inability to class switch and only IgM production.
      • Patients are susceptible to extracellular bacteria and lack sufficient cell-mediated immunity.
    • AID Deficiency (activation-induced cytidine deaminase deficiency):
      • Mutation in AID, which is required for initiation of somatic hypermutation and class switching.
      • Produces normal or high IgM levels with low or absent IgG, IgA, and IgE.
      • Patients experience recurrent bacterial respiratory and GI infections.
    • Common Variable Immunodeficiency (CVID):
      • Caused by a variety of mutations.
      • Characterized by very low serum levels of at least two Ig isotypes, including IgG, IgA, and/or IgM.
      • Lack of antibody response to infection and vaccination, leading to frequent infections and a variety of other autoimmune conditions.
      • Diagnosed throughout life with a complex interplay of genetic and environmental factors.
      • Treatment: IVIG (intravenous immunoglobulin) or SCIG (subcutaneous immunoglobulin) infusions.

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    Immunology Session 26 Primary Immunodeficiencies PDF

    Description

    Explore the intricacies of primary immunodeficiencies caused by genetic mutations and their impact on the immune system. This quiz covers various deficiencies, their features, and the consequences of impaired immune cell function. Delve into the specifics of complement deficiencies and their role in increasing infection susceptibility.

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