Immunoglobulin Deficiencies and Autoimmune Disorders
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Questions and Answers

What is the primary immunoglobulin deficiency identified in IgA deficiency?

  • Low serum and mucosal IgG
  • Low serum and mucosal IgE
  • Low serum and mucosal IgA (correct)
  • Low serum and mucosal IgM

    • Which of the following characterizes Hyper-IgM syndrome?

  • Normal CD40 receptor function in B cells
  • High levels of IgA and IgE
  • Elevated IgM due to CD40L mutations (correct)
  • Low IgM and normal IgG

    • Which condition is specifically linked to the WASP gene mutation?

  • Hyper-IgM syndrome
  • IgA deficiency
  • Complement deficiencies
  • Wiskott-Aldrich syndrome (correct)

    • What is a significant consequence of complement deficiencies involving C5-C9?

    <p>Increased risk for Neisseria infections</p> Signup and view all the answers

    What is the prevalence of autoimmune disorders in the US?

    <p>1%-2%</p> Signup and view all the answers

    How do regulatory T cells help prevent autoimmunity?

    <p>By suppressing T-cell activation</p> Signup and view all the answers

    Which autoimmune syndrome results from mutations in the AIRE gene?

    <p>Autoimmune polyendocrine syndrome</p> Signup and view all the answers

    What characterizes the immune response in individuals with IgA deficiency?

    <p>Recurrent mucosal infections</p> Signup and view all the answers

    Which population shows the highest prevalence of Systemic Lupus Erythematosus?

    <p>Middle-aged females, particularly of African American and Hispanic descent</p> Signup and view all the answers

    What role do estrogen levels potentially play in autoimmune disorders?

    <p>Reduce apoptosis of self-reactive B cells</p> Signup and view all the answers

    Which mechanism is NOT involved in the pathogenesis of Systemic Lupus Erythematosus?

    <p>Direct destruction of tissue by cytotoxic T cells</p> Signup and view all the answers

    What is a common clinical finding in individuals with Systemic Lupus Erythematosus?

    <p>Raynaud phenomenon</p> Signup and view all the answers

    Which polymorphism is associated with increased susceptibility to autoimmune disorders?

    <p>PTPN22 polymorphisms</p> Signup and view all the answers

    What is a significant consequence of DNA antigens activating TLRs in autoimmune conditions?

    <p>Amplification of immune response resulting in IFN-α production</p> Signup and view all the answers

    Which symptom is typically associated with relapses in autoimmune disorders?

    <p>Fever, weight loss, and persistent lymphadenopathy</p> Signup and view all the answers

    What condition is primarily caused by FOXP3 mutations?

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

    CD25 polymorphisms are known to be linked with autoimmune conditions such as multiple sclerosis and type 2 diabetes.

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

    Women of childbearing age are less likely to experience autoimmune disorders due to higher estrogen levels.

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

    Systemic lupus erythematosus primarily affects elderly males.

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

    Antigen-antibody complexes in systemic lupus erythematosus can lead to damage in multiple tissues through type I hypersensitivity reactions.

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

    Environmental triggers can activate self-reactive lymphocytes, leading to autoimmune disorders through mechanisms like molecular mimicry.

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

    Deficiency of early complement proteins C1q, C4, and C2 is associated with increased risk of developing systemic lupus erythematosus.

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

    Classic symptoms of systemic lupus erythematosus include fever, weight gain, and psychological disturbances.

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

    Oral or nasopharyngeal ulcers in systemic lupus erythematosus are usually painful.

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

    IgA deficiency primarily results in increased risk for bacterial infections in early childhood.

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

    Wiskott-Aldrich syndrome is characterized by thrombocytopenia, eczema, and recurrent infections due to a mutation in the WASP gene.

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

    C5-C9 complement deficiencies lead to an increased risk of infections primarily caused by Escherichia coli.

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

    Hyper-IgM syndrome results from the inability of B cells to undergo class switching due to mutated CD40L or CD40.

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

    Autoimmune disorders have a prevalence rate in the US of approximately 5%-10%.

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

    Regulatory T cells contribute to autoimmunity by enhancing T-cell activation.

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

    Increased levels of IgA, IgG, and IgE can lead to recurrent pyogenic infections.

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

    Mutations in the AIRE gene lead to autoimmune lymphoproliferative syndrome (ALPS).

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

    What is the primary immunological consequence of IgA deficiency?

    <p>Increased risk for mucosal infections, especially viral.</p> Signup and view all the answers

    How do mutations in CD40L or CD40 affect B-cell activation in Hyper-IgM syndrome?

    <p>They prevent the delivery of the second signal necessary for B-cell activation, inhibiting cytokine production for class switching.</p> Signup and view all the answers

    Which type of infections are individuals with complement deficiencies, particularly C5-C9, more vulnerable to?

    <p>Infections primarily caused by Neisseria species, like N gonorrhoeae and N meningitidis.</p> Signup and view all the answers

    What role do regulatory T cells play in maintaining self-tolerance?

    <p>They suppress autoimmunity by blocking T-cell activation and producing anti-inflammatory cytokines.</p> Signup and view all the answers

    What is the main clinical manifestation of Wiskott-Aldrich syndrome?

    <p>Thrombocytopenia, eczema, and recurrent infections.</p> Signup and view all the answers

    In cases of autoimmune disorders, what is typically compromised, leading to the condition?

    <p>Loss of self-tolerance, allowing self-reactive lymphocytes to cause tissue damage.</p> Signup and view all the answers

    What is characterized by edema of the skin and mucosal surfaces due to a complement deficiency?

    <p>Hereditary angioedema caused by Cl inhibitor deficiency.</p> Signup and view all the answers

    What is the connection between AIRE mutations and autoimmune disorders?

    <p>AIRE mutations lead to autoimmune polyendocrine syndrome due to impaired central tolerance development.</p> Signup and view all the answers

    What environmental factors may contribute to the onset of autoimmune disorders in genetically susceptible individuals?

    <p>Environmental triggers such as infections and UV exposure can activate self-reactive lymphocytes, potentially leading to autoimmune conditions.</p> Signup and view all the answers

    How does the immune system's response in systemic lupus erythematosus (SLE) typically manifest?

    <p>In SLE, the immune system creates antigen-antibody complexes that damage various tissues, often resulting in a type III hypersensitivity reaction.</p> Signup and view all the answers

    Describe one significant clinical manifestation of systemic lupus erythematosus.

    <p>A classic symptom of SLE is the malar 'butterfly' rash, which often appears after sun exposure.</p> Signup and view all the answers

    What role do early complement proteins C1q, C4, and C2 play in systemic lupus erythematosus?

    <p>Deficiency of these early complement proteins is associated with an increased risk of developing systemic lupus erythematosus.</p> Signup and view all the answers

    What is the relationship between sex and the prevalence of autoimmune disorders, especially systemic lupus erythematosus?

    <p>Autoimmune disorders, including SLE, are more common in women, particularly those of childbearing age.</p> Signup and view all the answers

    What is unique about the immune response observed in IPEX syndrome, and how is it related to FOXP3 mutations?

    <p>IPEX syndrome, caused by FOXP3 mutations, leads to immune dysregulation and results in a failure to control self-reactive T cells.</p> Signup and view all the answers

    What typically triggers the exacerbations or flares of systemic lupus erythematosus?

    <p>Exacerbations of SLE are often triggered by environmental factors such as UV light exposure, infections, or stress.</p> Signup and view all the answers

    Explain the concept of epitope spreading in autoimmune diseases.

    <p>Epitope spreading refers to the process where an immune response to one epitope leads to the activation of T cells against different epitopes, worsening autoimmunity.</p> Signup and view all the answers

    IgA deficiency is the most common immunoglobulin ______.

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

    Hyper-IgM syndrome is characterized by elevated ______.

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

    Wiskott-Aldrich syndrome is caused by a mutation in the ______ gene.

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

    C5-C9 complement deficiencies increase susceptibility to ______ infections.

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

    Autoimmune disorders involve a loss of self-______.

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

    The AIRE gene is crucial for establishing central ______ in the thymus.

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

    Regulatory T cells help suppress autoimmunity by producing anti-inflammatory ______.

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

    Complement deficiencies may lead to hereditary ______, characterized by skin edema.

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

    CD25 polymorphisms are associated with autoimmunity, including ______ and type 1 diabetes mellitus.

    <p>multiple sclerosis</p> Signup and view all the answers

    FOXP3 mutations can lead to a syndrome known as ______ which involves immune dysregulation.

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

    Systemic lupus erythematosus classically affects ______, especially those of childbearing age.

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

    Antigen-antibody complexes in systemic lupus erythematosus primarily damage tissues through a type ______ hypersensitivity reaction.

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

    Classic findings in systemic lupus erythematosus include a malar 'butterfly' rash and ______ or nasopharyngeal ulcers.

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

    A deficiency of early complement proteins, including C1q, C4, and C2, is associated with ______.

    <p>systemic lupus erythematosus</p> Signup and view all the answers

    Environmental triggers can lead to bystander activation or ______, playing a role in autoimmune disorders.

    <p>molecular mimicry</p> Signup and view all the answers

    In systemic lupus erythematosus, almost any ______ can be involved, leading to a wide range of symptoms.

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

    Match the following autoimmune conditions with their associated characteristics:

    <p>Multiple Sclerosis = CD25 polymorphisms IPEX Syndrome = FOXP3 mutations Systemic Lupus Erythematosus = Antigen-antibody complexes Type 1 Diabetes = Environmental triggers</p> Signup and view all the answers

    Match the following clinical manifestations with the corresponding autoimmune disorder:

    <p>Malar rash = Systemic Lupus Erythematosus Serositis = Systemic Lupus Erythematosus Thrombocytopenia = Wiskott-Aldrich Syndrome Raynaud phenomenon = Systemic Lupus Erythematosus</p> Signup and view all the answers

    Match the following terms with their definitions related to autoimmune diseases:

    <p>Epitope Spreading = Progressive disease with relapses and remissions Bystander Activation = Activation of lymphocytes by unrelated antigens Molecular Mimicry = Pathogen mimicking host antigens Type III Hypersensitivity = Damage from antigen-antibody complexes</p> Signup and view all the answers

    Match the following populations with their association with autoimmune diseases:

    <p>African American women = Higher prevalence of Systemic Lupus Erythematosus Older adults = Less dramatic gender bias in autoimmune diseases Children = Potential for Systemic Lupus Erythematosus Twins = Increased incidence of autoimmune disorders</p> Signup and view all the answers

    Match the following environmental factors with their role in autoimmune diseases:

    <p>UV damage = Poorly-cleared apoptotic debris Estrogen = Reduces apoptosis of self-reactive B cells HLA-B27 = Association with certain autoimmune conditions PTPN22 polymorphisms = Genetic susceptibility in autoimmunity</p> Signup and view all the answers

    Match the following immunological concepts with their descriptions:

    <p>Complement Deficiency = Associated with Systemic Lupus Erythematosus Self-reactive lymphocytes = Produce antibodies to host antigens IFN-α = Amplifies immune response to DNA antigens B cells = Undergo class switching in Hyper-IgM syndrome</p> Signup and view all the answers

    Match the following symptoms with their underlying autoimmune disorders:

    <p>Fatigue = Systemic Lupus Erythematosus Weight loss = Systemic Lupus Erythematosus Painless ulcers = Systemic Lupus Erythematosus Psychosis = Systemic Lupus Erythematosus</p> Signup and view all the answers

    Match the following terms related to autoimmune response mechanisms:

    <p>Tolerogenic Factors = Regulatory T cells preventing activation Autoimmunity Triggers = Environmental stimuli in genetically susceptible individuals Immunological Memory = Memory cells responding to previous infections Relapses = Episodic worsening of autoimmune conditions</p> Signup and view all the answers

    Match the immunoglobulin deficiency conditions with their characteristics:

    <p>IgA deficiency = Low serum and mucosal IgA; most common immunoglobulin deficiency Hyper-IgM syndrome = Characterized by elevated IgM and low IgA, IgG, and IgE Wiskott-Aldrich syndrome = Thrombocytopenia, eczema, and recurrent infections Complement deficiencies = Increased risk for Neisseria infections and hereditary angioedema</p> Signup and view all the answers

    Match the autoimmune disorders with their basic principles:

    <p>Central tolerance = Involves T-cell apoptosis or regulatory T cell generation AIRE mutations = Lead to autoimmune polyendocrine syndrome Fas apoptosis pathway mutations = Result in autoimmune lymphoproliferative syndrome (ALPS) Self-reactive lymphocytes = Regularly generated yet often develop tolerance</p> Signup and view all the answers

    Match the specific mutation/deficiency with its associated condition:

    <p>CD40L mutation = Hyper-IgM syndrome WASP gene mutation = Wiskott-Aldrich syndrome C5-C9 deficiencies = Increased risk for Neisseria infections C1 inhibitor deficiency = Hereditary angioedema</p> Signup and view all the answers

    Match the conditions with their prevalence or significance:

    <p>Autoimmune disorders = 1%-2% prevalence in US IgA deficiency = Increased risk for mucosal infections, especially viral Complement deficiencies = Result in increased vulnerability to certain infections AIRE gene mutations = Contribute to the pathogenesis of autoimmune syndromes</p> Signup and view all the answers

    Match the immune response characteristics with their respective deficiencies:

    <p>IgA deficiency = Asymptomatic in most patients despite increased infection risk Hyper-IgM syndrome = Impaired B-cell activation due to signaling issues Wiskott-Aldrich syndrome = Major cause of death is bleeding from thrombocytopenia Complement deficiencies = Contribution to recurrent pyogenic infections</p> Signup and view all the answers

    Match the gene mutations or pathways with their implications in autoimmune disorders:

    <p>AIRE mutations = Development of central tolerance issues Fas pathway mutations = Lead to defects in T and B cell apoptosis CD40L mutations = Cannot deliver second signals during B-cell activation WASP gene mutation = X-linked inheritance affecting immunity</p> Signup and view all the answers

    Match the symptoms or risks associated with immunodeficiencies:

    <p>IgA deficiency = Increased risk for bacterial infections Wiskott-Aldrich syndrome = Eczema as a significant clinical manifestation Hyper-IgM syndrome = Recurrent pyogenic infections due to poor opsonization Complement deficiencies = Hereditary angioedema characterized by edema</p> Signup and view all the answers

    Match the immune system features with the specific syndromes or conditions:

    <p>Recurrent infections = Common in IgA deficiency and Wiskott-Aldrich syndrome Autoimmune polyendocrine syndrome = AIRE mutations cause this condition Elevated IgM = Characteristic of Hyper-IgM syndrome Loss of self-tolerance = A key feature in autoimmune disorders</p> Signup and view all the answers

    Study Notes

    Immunoglobulin Deficiencies

    • Selective IgA Deficiency: Most common, low serum and mucosal IgA.
      • Increased risk of mucosal infections, especially viral, but many remain asymptomatic.
    • Hyper-IgM Syndrome: Elevated IgM, due to mutations in CD40L or CD40 receptor, impacting B-cell activation and class switching.
      • Results in low IgA, IgG, and IgE, leading to recurrent pyogenic infections at mucosal sites due to ineffective opsonization.
    • Wiskott-Aldrich Syndrome: Characterized by thrombocytopenia, eczema, and recurrent infections (both humoral and cellular immunity issues).
      • Caused by mutation in WASP gene, an X-linked condition. Bleeding is a major cause of death.
    • Complement Deficiencies:
      • C5-C9 deficiencies: Increased risk of Neisseria infections (gonorrhea and meningitis).
      • C1 inhibitor deficiency: Leads to hereditary angioedema with edema in the skin, especially around the eyes, and mucosal surfaces.

    Autoimmune Disorders

    • General Principles:
      • Characterized by immune-mediated destruction of self tissues.
      • US prevalence is 1-2%.
      • Loss of self-tolerance: Self-reactive lymphocytes normally undergo central (thymus and bone marrow) or peripheral tolerance mechanisms.
        • Central Tolerance (thymus): Apoptosis or generation of regulatory T cells. AIRE mutations cause autoimmune polyendocrine syndrome.
        • Central Tolerance (bone marrow): Receptor editing or B-cell apoptosis.
        • Peripheral Tolerance: Anergy or apoptosis of T and B cells. Fas apoptosis pathway mutations lead to autoimmune lymphoproliferative syndrome (ALPS).
        • Regulatory T cells: Suppress autoimmunity by blocking T-cell activation and producing anti-inflammatory cytokines (IL-10 and TGF-β). CD25 polymorphisms linked to autoimmunity (multiple sclerosis and type 1 diabetes), FOXP3 mutations lead to IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked).
      • More common in women, especially childbearing age. Estrogen may reduce apoptosis of self-reactive B cells.
      • Likely caused by environmental triggers in genetically susceptible individuals.
        • Increased incidence in twins.
        • Association with certain HLA types (e.g., HLA-B27) and PTPN22 polymorphisms.
        • Environmental triggers may lead to bystander activation or molecular mimicry.
      • Clinically progressive with relapses and remissions, often with overlapping features. Explained by epitope spreading.

    Systemic Lupus Erythematosus (SLE)

    • Chronic, systemic autoimmune disease with frequent flares and remissions.
    • Most common in middle-aged women, particularly African American and Hispanic women, but can occur in children and older adults (less gender bias).
    • Antigen-antibody complexes damage multiple tissues (type III hypersensitivity reaction).
      • Poorly cleared apoptotic debris (e.g., from UV damage) activates self-reactive lymphocytes, leading to antibody production against host nuclear antigens.
      • Antigen-antibody complexes are initially low level and taken up by dendritic cells.
      • DNA antigens activate TLRs, amplifying the immune response (IFN-α).
      • Antigen-antibody complexes are subsequently generated at higher levels and deposit in various tissues, causing disease.
      • Deficiency of early complement proteins (C1q, C4, and C2) associated with SLE.
    • Almost any tissue can be affected. Classic findings include:
      • Fever, weight loss, fatigue, lymphadenopathy, and Raynaud phenomenon.
      • 'Butterfly' rash across the face or discoid rash, especially after sun exposure.
      • Oral or nasopharyngeal ulcers (usually painless).
      • Arthritis affecting at least two joints.
      • Serositis (pleuritis and pericarditis).
      • Psychosis or seizures.
      • Renal damage.

    Immunoglobulin Deficiencies

    • Selective IgA Deficiency: Most common immunoglobulin deficiency, with low serum and mucosal IgA.
    • Increased Risk of Mucosal Infections: Patients with IgA deficiency are at higher risk for viral infections in the mucosal lining. Most patients are asymptomatic.
    • Hyper-IgM Syndrome: High IgM levels due to mutations in CD40L (on helper T cells) or CD40 receptor (on B cells).
    • Inability to Deliver Second Signal: Mutations prevent the delivery of the second signal to helper T cells during B-cell activation, halting immunoglobulin class switching.
    • Low IgG, IgA, and IgE: Deficiency in these immunoglobulins leads to frequent pyogenic infections, particularly at mucosal sites.
    • Wiskott-Aldrich Syndrome: Characterized by thrombocytopenia, eczema, and recurrent infections, affecting both humoral and cellular immunity.
    • Bleeding: A major cause of death in individuals with Wiskott-Aldrich Syndrome.
    • Mutation in WASP Gene: X-linked genetic disorder caused by mutations in the WASP gene.
    • Complement Deficiencies: Deficiencies in complement proteins can increase susceptibility to infections.
    • C5-C9 Deficiencies: Increased risk for Neisseria infections, including N gonorrhoeae and N meningitidis.
    • C1 Inhibitor Deficiency: Leads to hereditary angioedema, characterized by skin and mucosal swelling.

    Autoimmune Disorders

    • Immune-mediated Damage of Self Tissues: Autoimmune disorders result in the body's immune system attacking its own tissues.
    • Loss of Self-Tolerance: Breakdown in the immune system's ability to distinguish self from non-self, leading to the activation of self-reactive lymphocytes.
    • Central Tolerance: Established in the thymus and bone marrow, eliminating or regulating self-reactive lymphocytes.
      • AIRE Mutations: Result in autoimmune polyendocrine syndrome, a condition affecting multiple endocrine glands.
    • Peripheral Tolerance: Mechanisms that suppress self-reactive lymphocytes that escape central tolerance.
      • Fas Apoptosis Pathway Mutations: Associated with autoimmune lymphoproliferative syndrome (ALPS).
    • Regulatory T Cells: Suppress autoimmunity by blocking T-cell activation and producing anti-inflammatory cytokines.
      • CD25 Polymorphisms: Linked to autoimmune diseases like multiple sclerosis (MS) and type 1 diabetes mellitus (T1DM).
      • FOXP3 Mutations: Cause IPEX syndrome, an X-linked disorder characterized by immune dysregulation, polyendocrinopathy, and enteropathy.
    • Women More Susceptible: Autoimmune disorders are more prevalent in women, particularly those of childbearing age.
    • Estrogen's Role: Estrogen may play a role by reducing apoptosis of self-reactive B cells.
    • Environmental Triggers in Genetically Susceptible Individuals: Often contribute to the development of autoimmune disorders.
      • Twin Studies: Higher incidence of autoimmune disorders in twins suggests a genetic component.
      • HLA Types and PTPN22 Polymorphisms: Associations with certain HLA types and PTPN22 genetic variations have been observed in individuals with autoimmune disorders.
      • Bystander Activation and Molecular Mimicry: Environmental triggers can lead to immune system activation against self-antigens.
    • Clinical Progression: Autoimmune disorders have a fluctuating course with periods of flares and remissions and often exhibit overlapping features.
      • Epitope Spreading: The autoimmune response can expand to target additional self-antigens, contributing to the development of autoimmune disorders.

    Systemic Lupus Erythematosus (SLE)

    • Chronic Systemic Autoimmune Disease: SLE involves multiple organs and systems with intermittent periods of flares and remissions.
    • Middle-aged Females Predisposed: SLE predominately affects middle-aged women, especially those of African American and Hispanic descent.
    • Antigen-antibody Complex Damage: Damage to various tissues is mediated by antigen-antibody complexes (type III hypersensitivity reaction).
      • Apoptotic Debris: Poorly cleared apoptotic debris, for instance, from UV damage, triggers the production of autoantibodies against nuclear antigens by self-reactive lymphocytes.
      • TLR Activation: DNA antigens engage Toll-like receptors (TLRs), amplifying the inflammatory response.
      • Complement Protein Deficiency: Low levels of C1q, C4, and C2 complement proteins are associated with SLE.
    • Multiple Tissue Involvement: SLE can affect almost any tissue in the body.
      • Classic Symptoms: Fever, weight loss, fatigue, lymphadenopathy, and Raynaud's phenomenon.
      • Skin Manifestations: Malar "butterfly" rash, discoid rash, especially triggered by sunlight exposure.
      • Oral and Nasopharyngeal Ulcers: Usually painless.
      • Arthritis: Joint inflammation affecting two or more joints.
      • Serositis: Inflammation of the pleural and pericardial linings.
      • Neurological Complications: Psychosis, seizures.
      • Kidney Damage: Renal involvement is a major complication.

    Immunodeficiency Disorders

    • X-Linked Agammaglobulinemia (Bruton's Agammaglobulinemia): Absence of mature B cells leads to severely impaired antibody production, recurrent bacterial infections (especially encapsulated bacteria), and low serum immunoglobulin levels.
    • Common Variable Immunodeficiency (CVID): Diverse genetic and environmental causes, leading to low levels of IgG, IgA, and IgM. Recurrent bacterial and viral infections, as well as chronic diarrhea and autoimmune disorders, are common.
    • Selective IgA Deficiency: Most common immunoglobulin deficiency, featuring low serum and mucosal IgA levels. Predisposes individuals to viral infections, especially at mucosal surfaces, but many remain asymptomatic.
    • Hyper-IgM Syndrome: Characterized by elevated IgM levels, caused by mutations in CD40L or CD40 receptor, which are essential for B-cell activation and class switching. This results in low IgA, IgG, and IgE, leading to recurrent infections at mucosal surfaces.
    • Wiskott-Aldrich Syndrome: X-linked recessive disorder caused by mutations in the WASP gene, leading to thrombocytopenia, eczema, and recurrent infections due to impaired humoral and cellular immunity. Bleeding is a major concern.
    • Complement Deficiencies: Deficiencies in C5-C9 increase susceptibility to infections caused by Neisseria species (N gonorrhoeae and N meningitidis). Cl inhibitor deficiency results in hereditary angioedema, characterized by edema of the skin and mucosal surfaces.

    Autoimmune Disorders

    • General Principles: These disorders involve an immune response directed against self-antigens, leading to tissue damage. They are more common in females, especially of childbearing age, and are likely triggered by environmental factors in genetically susceptible individuals.
    • Loss of self-tolerance: normally self-reactive lymphocytes are eliminated or suppressed. Mutations in AIRE gene lead to autoimmune polyendocrine syndrome. Mutations in Fas apoptosis pathway result in autoimmune lymphoproliferative syndrome.
    • Systemic Lupus Erythematosus (SLE): Chronic, systemic autoimmune disease characterized by the formation of antigen-antibody complexes that damage multiple tissues. Commonly affects middle-aged women, especially African Americans and Hispanics.
    • Classic features: Butterfly rash, discoid rash, oral/nasopharyngeal ulcers, arthritis, serositis (pleuritis, pericarditis), psychosis, seizures, and renal damage.
    • Pathogenesis: Apoptotic debris, especially from UV damage, activates self-reactive lymphocytes, triggering the production of antibodies against host nuclear antigens. These antibodies form antigen-antibody complexes, which deposit in various tissues causing inflammation.
    • Genetic predisposition: Associations with specific MHC class II alleles (e.g., HLA-DR2 and HLA-DR3) and other genetic factors influence susceptibility.

    Immunoglobulin Deficiencies

    • IgA Deficiency: Most common immunoglobulin deficiency, marked by low serum and mucosal IgA.
      • Patients usually asymptomatic, but experience increased risk of mucosal infections, particularly viral.
    • Hyper-IgM Syndrome: Characterized by elevated IgM levels.
      • Caused by mutated CD40L (on helper T cells) or CD40 receptor (on B cells).
      • This disrupts B-cell activation and class switching, resulting in low levels of IgA, IgG, and IgE.
      • Patients suffer from recurrent pyogenic infections due to poor opsonization, especially at mucosal sites.
    • Wiskott-Aldrich Syndrome: Characterized by thrombocytopenia, eczema, and recurrent infections (defective humoral and cellular immunity).
      • Caused by a mutation in the WASP gene (X-linked).
      • Bleeding is a major cause of death.
    • Complement Deficiencies:
      • C5-C9 deficiencies: Increased risk of Neisseria infections (N gonorrhoeae and N meningitidis).
      • C1 inhibitor deficiency: Results in hereditary angioedema, causing edema of the skin and mucosal surfaces.

    Autoimmune Disorders

    • General Principles:
      • Characterized by immune-mediated damage to self tissues.
      • Involves loss of self-tolerance, where self-reactive lymphocytes are normally eliminated or controlled.
      • Central tolerance mechanisms in the thymus (T-cell apoptosis or regulatory T cell generation) and bone marrow (receptor editing or B-cell apoptosis) are crucial.
      • Peripheral tolerance mechanisms like anergy and apoptosis of T and B cells are also important.
      • Regulatory T cells suppress autoimmunity by blocking T-cell activation and producing anti-inflammatory cytokines.
      • More common in women, especially those of childbearing age.
      • Likely involves environmental triggers in genetically susceptible individuals.
      • Characterized by clinical progression with relapses and remissions.
    • Systemic Lupus Erythematosus (SLE):
      • Chronic, systemic autoimmune disease with flares and remissions.
      • Typically affects middle-aged women, particularly African American and Hispanic women.
      • Antigen-antibody complexes damage multiple tissues (type III hypersensitivity reaction).
      • Poorly cleared apoptotic debris can trigger self-reactive lymphocytes to produce antibodies against host nuclear antigens.
      • Deficiency of early complement proteins (C1q, C4, and C2) is associated with SLE.
      • Can involve almost any tissue, with classic findings:
        • Fever, weight loss, fatigue, lymphadenopathy, and Raynaud phenomenon.
        • Malar 'butterfly' rash or discoid rash, especially upon sun exposure.
        • Oral or nasopharyngeal ulcers (usually painless).
        • Arthritis (usually involving ≥ 2 joints).
        • Serositis (pleuritis and pericarditis).
        • Psychosis or seizures.
        • Renal damage.

    Immunoglobulin Deficiency

    • IgA deficiency is the most common immunoglobulin deficiency.
    • Patients with IgA deficiency have low serum and mucosal IgA and are at increased risk for mucosal infection, especially viral, however, most are asymptomatic.
    • Hyper-IgM syndrome is characterized by elevated IgM due to mutated CD40L or CD40 receptor.
    • Patients with Hyper-IgM syndrome are at increased risk for recurrent pyogenic infections at mucosal sites due to poor opsonization.
    • Wiskott-Aldrich syndrome is characterized by thrombocytopenia, eczema, and recurrent infections; it is X-linked.

    Complement Deficiencies

    • C5-C9 deficiencies increase risk for Neisseria infection.
    • C1 inhibitor deficiency results in hereditary angioedema, which clinically manifests as edema of the skin and mucosal surfaces.

    Autoimmune Disorders

    • Autoimmune disorders are characterized by immune-mediated damage of self tissues and can involve loss of central or peripheral tolerance.
    • Classic autoimmune disorder features include:
    • More common in women, often affecting women of childbearing age.
    • Estrogen may reduce apoptosis of self-reactive B cells.
    • Environmental triggers may lead to bystander activation or molecular mimicry.
    • Autoimmune disorders are clinically progressive with relapses and remissions.
    • Autoimmune disorders often show overlapping features, which can be explained by epitope spreading.

    Systemic Lupus Erythematosus (SLE)

    • SLE is a chronic, systemic autoimmune disease that can be characterized by flares and remissions.
    • The underlying cause of SLE is unclear, but it may be due to poorly cleared apoptotic debris, which activates self-reactive lymphocytes that then produce antibodies to host nuclear antigens.
    • SLE is characterized by a variety of clinical symptoms, including:
    • Fever
    • Weight loss
    • Fatigue
    • Lymphadenopathy
    • Raynaud phenomenon
    • Malar 'butterfly' rash
    • Discoid rash
    • Oral or nasopharyngeal ulcers (usually painless)
    • Arthritis (usually involving ≥ 2 joints)
    • Serositis (pleuritis and pericarditis)
    • Psychosis or seizures
    • Renal damage

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    Description

    This quiz covers essential knowledge on various immunoglobulin deficiencies, including Selective IgA Deficiency, Hyper-IgM Syndrome, and Wiskott-Aldrich Syndrome. Additionally, it touches on complement deficiencies and their implications. Test your understanding of these conditions and their effects on the immune system.

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