Fundamentals of Pathology and Immunodeficiency
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Questions and Answers

What is the role of IL-12 secreted by macrophages in relation to CD4 + helper T cells?

  • To induce differentiation into TH1 subtype (correct)
  • To promote B cell maturation
  • To convert macrophages to epithelioid histiocytes
  • To directly kill pathogens

    • Which condition is primarily characterized by the developmental failure of the third and fourth pharyngeal pouches?

  • Adenosine Deaminase Deficiency
  • DiGeorge Syndrome (correct)
  • Severe Combined Immunodeficiency (SCID)
  • Cytokine Receptor Defect

    • What is a consequence of adenosine deaminase (ADA) deficiency?

  • Overproduction of white blood cells
  • Buildup of toxic metabolites leading to lymphocyte toxicity (correct)
  • Increased T cell count due to lack of destruction
  • Enhanced cytokine signaling

    • What is the primary immunodeficiency condition associated with T-cell deficiency and hypocalcemia?

    <p>DiGeorge Syndrome</p> Signup and view all the answers

    Which of the following is NOT a characteristic of Severe Combined Immunodeficiency (SCID)?

    <p>Normal function of cytokine receptors</p> Signup and view all the answers

    Which cells are converted to epithelioid histiocytes by the action of IFN-γ?

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

    What genetic deletion is associated with DiGeorge Syndrome?

    <p>22q11</p> Signup and view all the answers

    What kind of maturation is necessary for both B and T cells in the context of cytokine receptor defects?

    <p>Maturation through cytokine signaling</p> Signup and view all the answers

    What genetic mutation is primarily associated with the autoimmune polyendocrine syndrome?

    <p>AIRE mutation</p> Signup and view all the answers

    Which autoimmune disorder is characterized by the loss of self-tolerance in T cells, leading to widespread autoimmune reactions?

    <p>Autoimmune lymphoproliferative syndrome (ALPS)</p> Signup and view all the answers

    What is a consequence of deficiencies in the C5-C9 complement proteins?

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

    How does estrogen influence autoimmune disorders in women of childbearing age?

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

    What is a common feature of autoimmune disorders regarding their prevalence?

    <p>Greater incidence in twins compared to single births</p> Signup and view all the answers

    What is the primary cause of X-linked agammaglobulinemia?

    <p>Mutated Bruton tyrosine kinase</p> Signup and view all the answers

    Which of the following infections are most commonly associated with common variable immunodeficiency (CVID)?

    <p>Bacterial, enterovirus, and Giardia lamblia infections</p> Signup and view all the answers

    What is the most common immunoglobulin deficiency?

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

    What characterizes Hyper-IgM syndrome?

    <p>Elevated IgM with low IgA, IgG, and IgE</p> Signup and view all the answers

    At what stage of life do symptoms of X-linked agammaglobulinemia typically present?

    <p>After 6 months of life</p> Signup and view all the answers

    Which immunodeficiency is primarily associated with an increased risk for autoimmune disease and lymphoma?

    <p>Common variable immunodeficiency (CVID)</p> Signup and view all the answers

    What is a significant consequence of IgA deficiency in patients?

    <p>Heightened susceptibility to mucosal infections</p> Signup and view all the answers

    What type of infections should patients with X-linked agammaglobulinemia avoid?

    <p>Live vaccines</p> Signup and view all the answers

    Thrombocytopenia, eczema, and recurrent infections are indicative of a condition related to a mutation in the WASP gene.

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

    Complement deficiencies C5-C9 are primarily associated with an increased risk of infections caused by Streptococcus species.

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

    Immune-mediated damage of self tissues is not characteristic of autoimmune disorders.

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

    The presence of AIRE mutations can lead to autoimmune lymphoproliferative syndrome (ALPS).

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

    Regulatory T cells suppress autoimmunity by producing inflammatory cytokines such as IL-10.

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

    Macrophages present antigen via MHC class II to CD8 + cytotoxic T cells.

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

    DiGeorge Syndrome is associated with a 22q11 microdeletion, leading to T-cell deficiency and hypocalcemia.

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

    Severe Combined Immunodeficiency (SCID) only affects humoral immunity and has no effect on cell-mediated immunity.

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

    Adenosine deaminase (ADA) deficiency results in the accumulation of toxic metabolites that affect lymphocytes.

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

    TH1 cells secrete IL-12, stimulating the differentiation of CD4 + helper T cells.

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

    MHC class II deficiency impairs the activation and cytokine production of CD8 + cytotoxic T cells.

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

    The lack of parathyroid glands in DiGeorge Syndrome can lead to hyposensitivity to calcium.

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

    Macrophages transform into giant cells in response to IFN-γ stimulation.

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

    Patients with X-linked agammaglobulinemia are protected by maternal antibodies for the first 12 months of life.

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

    Common Variable Immunodeficiency (CVID) is characterized by an increased risk of granulomatous infections.

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

    In Hyper-IgM syndrome, the defect lies in the ability of T cells to deliver a second signal to B cells during activation.

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

    IgA deficiency is the rarest form of immunoglobulin deficiency.

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

    Patients with IgA deficiency typically experience a higher frequency of bacterial infections compared to viral infections.

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

    Bruton tyrosine kinase mutations are linked to the maturation failure of pre- and pro-B cells.

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

    Wiskott-Aldrich Syndrome is primarily characterized by an elevation in IgG levels.

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

    Maternal antibodies are ineffective against enteroviruses such as polio after the first 6 months in infants.

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

    What are the primary clinical features of Wiskott-Aldrich Syndrome, and what genetic mutation is this condition associated with?

    <p>Wiskott-Aldrich Syndrome is characterized by thrombocytopenia, eczema, and recurrent infections, resulting from a mutation in the WASP gene.</p> Signup and view all the answers

    Explain the consequences of a C5-C9 complement deficiency and the type of infections it predisposes individuals to.

    <p>C5-C9 complement deficiencies increase the risk of infections specifically caused by Neisseria species, such as N gonorrhoeae and N meningitidis.</p> Signup and view all the answers

    Discuss the role of regulatory T cells in maintaining self-tolerance and their relevance in autoimmune disorders.

    <p>Regulatory T cells suppress autoimmunity by inhibiting T-cell activation and producing anti-inflammatory cytokines like IL-10 and TGF-β, which help maintain self-tolerance.</p> Signup and view all the answers

    What is the significance of AIRE mutations in the context of autoimmune diseases?

    <p>AIRE mutations disrupt central tolerance in the thymus, leading to autoimmune polyendocrine syndrome due to the failure of T cells to recognize self-antigens.</p> Signup and view all the answers

    Outline the primary mechanisms leading to loss of self-tolerance in autoimmune disorders.

    <p>Loss of self-tolerance in autoimmune disorders can occur due to defective central tolerance mechanisms in the thymus and bone marrow or due to the failure of peripheral tolerance processes.</p> Signup and view all the answers

    What is the significance of MHC class II in the context of T-cell activation by macrophages?

    <p>MHC class II is crucial for presenting antigens to CD4+ helper T cells, enabling their activation and subsequent secretion of cytokines.</p> Signup and view all the answers

    How does IL-12 influence the differentiation of CD4+ helper T cells in response to macrophage activity?

    <p>IL-12 induces CD4+ helper T cells to differentiate into the TH1 subtype, driving cell-mediated immunity.</p> Signup and view all the answers

    Describe the clinical manifestations associated with DiGeorge Syndrome.

    <p>DiGeorge Syndrome presents with T-cell deficiency, hypocalcemia, and various cardiac and facial abnormalities.</p> Signup and view all the answers

    What role does adenosine deaminase (ADA) play in lymphocyte health?

    <p>ADA is essential for deaminating adenosine and deoxyadenosine; its deficiency results in toxic accumulation that is harmful to lymphocytes.</p> Signup and view all the answers

    In what way does MHC class II deficiency impact immune function?

    <p>MHC class II deficiency impairs the activation of CD4+ helper T cells, resulting in compromised cytokine production and immune response.</p> Signup and view all the answers

    How does IFN-γ influence macrophage transformation in immune responses?

    <p>IFN-γ converts macrophages into epithelioid histiocytes and giant cells, enhancing their ability to tackle infections.</p> Signup and view all the answers

    What are the consequences of cytokine receptor defects in terms of T and B cell maturation?

    <p>Cytokine receptor defects hinder the proliferation and maturation of B and T cells, leading to combined immunodeficiency.</p> Signup and view all the answers

    Explain the implications of the 22q11 microdeletion in DiGeorge Syndrome.

    <p>The 22q11 microdeletion results in the developmental failure of critical structures, leading to T-cell deficiency and other abnormalities.</p> Signup and view all the answers

    What mutation is responsible for the complete lack of immunoglobulin in X-linked agammaglobulinemia?

    <p>A mutation in Bruton tyrosine kinase.</p> Signup and view all the answers

    How does Hyper-IgM syndrome affect B-cell activation?

    <p>It prevents the delivery of a second signal to B cells, disrupting class switching.</p> Signup and view all the answers

    Which types of infections are individuals with Common Variable Immunodeficiency (CVID) particularly susceptible to?

    <p>Recurrent bacterial, enterovirus, and Giardia lamblia infections.</p> Signup and view all the answers

    Why should patients with X-linked agammaglobulinemia avoid live vaccines?

    <p>Because they lack sufficient immunoglobulin to mount a proper immune response.</p> Signup and view all the answers

    What is the most common immunoglobulin deficiency and what is its characteristic?

    <p>IgA deficiency, characterized by low serum and mucosal IgA levels.</p> Signup and view all the answers

    What consequence does low IgA, IgG, and IgE have in Hyper-IgM syndrome?

    <p>It results in recurrent pyogenic infections due to poor opsonization.</p> Signup and view all the answers

    In Wiskott-Aldrich syndrome, what are the classic triad of symptoms?

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

    At what point in life do symptoms of X-linked agammaglobulinemia typically present, and why?

    <p>Symptoms usually present after 6 months due to the waning of maternal antibodies.</p> Signup and view all the answers

    Wiskott-Aldrich Syndrome is characterized by thrombocytopenia, eczema, and recurrent ______.

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

    C5-C9 deficiencies are associated with an increased risk of ______ infections.

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

    The loss of self-tolerance in autoimmune disorders involves self-reactive lymphocytes developing tolerance in the ______.

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

    AIRE mutations can lead to autoimmune ______ syndrome.

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

    Regulatory T cells suppress autoimmunity by blocking T-cell activation and producing anti-inflammatory ______.

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

    Macrophages present antigen via MHC class II to ______ cells.

    <p>CD4+ helper T</p> Signup and view all the answers

    The 22q11 microdeletion is associated with ______ syndrome.

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

    Adenosine deaminase (ADA) deficiency leads to the buildup of ______, which is toxic to lymphocytes.

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

    IFN-γ secreting TH1 cells convert macrophages to ______ histiocytes.

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

    Severe Combined Immunodeficiency (SCID) results in defective ______-mediated and humoral immunity.

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

    MHC class II is necessary for the activation of ______ T cells.

    <p>CD4+ helper</p> Signup and view all the answers

    Patients with DiGeorge syndrome often present with ______ due to a lack of parathyroid glands.

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

    In Hyper-IgM syndrome, T cells fail to adequately deliver a second signal to ______ cells during activation.

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

    X-linked agammaglobulinemia is characterized by a complete lack of ______ due to disordered B-cell maturation.

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

    In common variable immunodeficiency (CVID), there is a low level of ______ due to B-cell or helper T-cell defects.

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

    IgA deficiency is the most common type of ______ deficiency.

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

    Hyper-IgM syndrome is characterized by elevated ______ levels due to a failure in B-cell activation.

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

    Patients with X-linked agammaglobulinemia must avoid live ______ as they are at high risk for infections.

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

    In the context of Hyper-IgM syndrome, the necessary cytokines for immunoglobulin ______ are not produced.

    <p>class switching</p> Signup and view all the answers

    Wiskott-Aldrich syndrome is characterized by thrombocytopenia, eczema, and recurrent ______.

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

    Patients with IgA deficiency are at an increased risk for ______ infections, particularly viral ones.

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

    Match the following conditions with their associated features:

    <p>Wiskott-Aldrich Syndrome = Thrombocytopenia, eczema, recurrent infections, X-linked mutation in the WASP gene C5-C9 Complement Deficiency = Increased risk for Neisseria infections (N gonorrhoeae and N meningitidis) AIRE Mutations = Lead to autoimmune polyendocrine syndrome Cl Inhibitor Deficiency = Causes hereditary angioedema, skin and mucosal edema</p> Signup and view all the answers

    Match the following principles of autoimmunity with their implications:

    <p>Loss of self-tolerance = Results in the generation of self-reactive lymphocytes Central tolerance in thymus = Leads to T-cell apoptosis or regulatory T cell generation Fas Apoptosis Pathway Mutations = Result in autoimmune lymphoproliferative syndrome (ALPS) Regulatory T cells = Suppress autoimmunity by blocking T-cell activation</p> Signup and view all the answers

    Match the autoimmune disorders with their characteristics:

    <p>Multiple Sclerosis = Associated with CD25 polymorphisms IPEX Syndrome = Results from FOXP3 mutations Autoimmune Lymphoproliferative Syndrome = Caused by mutations in the Fas apoptosis pathway Autoimmune Polyendocrine Syndrome = Linked to AIRE mutations</p> Signup and view all the answers

    Match the following types of responses with their conditions:

    <p>Hereditary Angioedema = Caused by Cl inhibitor deficiency Increased risk of granulomatous infections = Common Variable Immunodeficiency (CVID) Prevalence in women of childbearing age = Autoimmune disorders X-linked Agammaglobulinemia = Characterized by a mutation in Bruton tyrosine kinase</p> Signup and view all the answers

    Match the following features of immune regulation with their effects:

    <p>IL-10 = Anti-inflammatory cytokine produced by regulatory T cells TGF-β = Involved in suppressing immune responses Environmental triggers = Increased incidence in genetically-susceptible individuals Estrogen = May reduce apoptosis in self-reactive B cells</p> Signup and view all the answers

    Match the following immunodeficiencies with their primary characteristics:

    <p>DiGeorge Syndrome = Developmental failure of the third and fourth pharyngeal pouches Severe Combined Immunodeficiency (SCID) = Defective cell-mediated and humoral immunity Adenosine deaminase (ADA) deficiency = Buildup of toxic metabolites affecting lymphocytes MHC class II deficiency = Impairment of CD4 + helper T cell activation</p> Signup and view all the answers

    Match the following cytokines with their effects on T cells:

    <p>IL-12 = Induces differentiation of CD4 + cells into TH1 subtype IFN-γ = Converts macrophages to epithelioid histiocytes IL-10 = Suppresses autoimmunity IL-2 = Stimulates T cell proliferation</p> Signup and view all the answers

    Match the following conditions with their resulting clinical manifestations:

    <p>DiGeorge Syndrome = T-cell deficiency and hypocalcemia Severe Combined Immunodeficiency (SCID) = Increased susceptibility to infections Adenosine deaminase (ADA) deficiency = Accumulation of toxic metabolites leading to immune dysfunction MHC class II deficiency = Defective activation of CD4 + helper T cells</p> Signup and view all the answers

    Match the following terms with their descriptions:

    <p>CD4 + T cells = Helper T cells that aid in immune response Macrophages = Present antigens via MHC class II Epithelioid histiocytes = Transformed macrophages in chronic inflammation Giant cells = Multinucleated cells formed by macrophage fusion</p> Signup and view all the answers

    Match the following etiologies of SCID with their definitions:

    <p>Cytokine receptor defects = Necessary for B and T cell proliferation and maturation Adenosine deaminase (ADA) deficiency = Toxic to lymphocytes due to adenosine buildup MHC class II deficiency = Impairment of CD4 + helper T cell activation X-linked SCID = Defect in lymphocyte development resulting from IL-2 receptor gene mutation</p> Signup and view all the answers

    Match the following immunological factors with their effects:

    <p>IFN-γ = Stimulates macrophage activation IL-12 = Drives TH1 differentiation IL-4 = Promotes TH2 differentiation TGF-β = Inhibits T cell proliferation</p> Signup and view all the answers

    Match the following genetic alterations to their associated syndromes:

    <p>22q11 microdeletion = DiGeorge Syndrome Bruton tyrosine kinase mutations = X-linked agammaglobulinemia WASP gene mutation = Wiskott-Aldrich Syndrome AIRE gene mutations = Autoimmune lymphoproliferative syndrome (ALPS)</p> Signup and view all the answers

    Match the following immune cells with their functions:

    <p>CD4 + T cells = Coordinate immune responses CD8 + T cells = Cytotoxic functions B cells = Antibody production Natural Killer cells = Destruction of virus-infected cells</p> Signup and view all the answers

    Match the immunodeficiency conditions with their characteristics:

    <p>X-Linked Agammaglobulinemia = Complete lack of immunoglobulin due to disordered B-cell maturation Common Variable Immunodeficiency (CVID) = Low immunoglobulin due to B-cell or helper T-cell defects IgA Deficiency = Low serum and mucosal IgA; most common immunoglobulin deficiency Hyper-IgM Syndrome = Characterized by elevated IgM due to mutated CD40L or CD40 receptor</p> Signup and view all the answers

    Match the conditions with their specific infections associated:

    <p>X-Linked Agammaglobulinemia = Recurrent bacterial, enterovirus, and Giardia lamblia infections Common Variable Immunodeficiency (CVID) = Increased risk for bacterial, enterovirus, and Giardia lamblia infections IgA Deficiency = Increased risk for mucosal infections, especially viral Wiskott-Aldrich Syndrome = Thrombocytopenia, eczema, and recurrent infections</p> Signup and view all the answers

    Match the immunodeficiency disorders with their treatment strategies:

    <p>X-Linked Agammaglobulinemia = Sterile isolation and stem cell transplantation Common Variable Immunodeficiency (CVID) = Immunoglobulin replacement therapy IgA Deficiency = Monitor for viral infections Hyper-IgM Syndrome = Gamma globulin therapy to prevent infections</p> Signup and view all the answers

    Match the immunodeficiency conditions with the genetic mutations associated:

    <p>X-Linked Agammaglobulinemia = Mutation in Bruton's tyrosine kinase Common Variable Immunodeficiency (CVID) = Defects in B-cell or helper T-cell function IgA Deficiency = No specific mutation identified Hyper-IgM Syndrome = Mutation in CD40L or CD40 receptor</p> Signup and view all the answers

    Match the immunodeficiency conditions with their onset of symptoms:

    <p>X-Linked Agammaglobulinemia = Presents after 6 months of life Common Variable Immunodeficiency (CVID) = Usually in late childhood IgA Deficiency = Most patients are asymptomatic Hyper-IgM Syndrome = Can present in childhood with recurrent infections</p> Signup and view all the answers

    Match the features of immunodeficiency with the corresponding disease:

    <p>X-Linked Agammaglobulinemia = Maternal antibodies protect for first 6 months Common Variable Immunodeficiency (CVID) = Increased risk for autoimmune disease and lymphoma IgA Deficiency = Most prevalent immunoglobulin deficiency Wiskott-Aldrich Syndrome = Eczema, thrombocytopenia, and immune deficiency</p> Signup and view all the answers

    Match the immunodeficiency condition with the type of immunoglobulin typically affected:

    <p>X-Linked Agammaglobulinemia = IgG, IgM, IgA Common Variable Immunodeficiency (CVID) = IgG and IgA IgA Deficiency = IgA Hyper-IgM Syndrome = IgM predominantly elevated with low IgA, IgG, and IgE</p> Signup and view all the answers

    Match the immunodeficiency conditions with the risk factors involved:

    <p>X-Linked Agammaglobulinemia = Recurrent opportunistic infections and avoidance of live vaccines Common Variable Immunodeficiency (CVID) = Increased risk for granulomatous infections IgA Deficiency = Higher frequency of bacterial infections compared to viral Hyper-IgM Syndrome = Poor opsonization leading to recurrent pyogenic infections</p> Signup and view all the answers

    Study Notes

    Fundamentals of Pathology

    • Macrophages process and present antigens to CD4+ helper T cells via MHC class II
    • This interaction leads to IL-12 secretion by macrophages, which induces CD4+ helper T cells to differentiate into the TH1 subtype
    • TH1 cells secrete IFN-γ, converting macrophages to epithelioid histiocytes and giant cells

    Primary Immunodeficiency

    • DiGeorge Syndrome:

      • Developmental failure of the third and fourth pharyngeal pouches
      • Due to 22q11 microdeletion
      • Presents with T-cell deficiency (lack of thymus), hypocalcemia (lack of parathyroids), and abnormalities of the heart, great vessels, and face

    • Severe Combined Immunodeficiency (SCID)

      • Defective cell-mediated and humoral immunity
      • Etiologies include:
        • Cytokine receptor defects
        • Adenosine deaminase (ADA) deficiency
        • MHC class II deficiency
      • Characterized by susceptibility to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines
      • Treatment involves sterile isolation and stem cell transplantation

    • X-Linked Agammaglobulinemia

      • Complete lack of immunoglobulin due to disordered B-cell maturation
      • Pre- and pro-B cells cannot mature
      • Due to mutated Bruton tyrosine kinase; X-linked
      • Presents after 6 months of life with recurrent bacterial, enterovirus, and Giardia lamblia infections; maternal antibodies are protective during the first 6 months of life
      • Live vaccines must be avoided

    • Common Variable Immunodeficiency (CVID)

      • Low immunoglobulin due to B-cell or helper T-cell defects
      • Increased risk for bacterial, enterovirus, and Giardia lamblia infections, usually in late childhood
      • Increased risk for autoimmune disease and lymphoma

    • IgA Deficiency:

      • Low serum and mucosal IgA; most common immunoglobulin deficiency
      • Increased risk for mucosal infection, especially viral; however, most patients are asymptomatic

    • Hyper-IgM Syndrome:

      • Characterized by elevated IgM
      • Due to mutated CD40L (on helper T cells) or CD40 receptor (on B cells)
      • Second signal cannot be delivered to helper T cells during B-cell activation
      • Consequently, cytokines necessary for immunoglobulin class switching are not produced
      • Low IgA, IgG, and IgE result in 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); bleeding is a major cause of death
      • Due to mutation in the WASP gene; X-linked

    • Complement Deficiencies:

      • C5-C9 deficiencies: increased risk for Neisseria infection (N gonorrhoeae and N meningitidis)
      • Cl inhibitor deficiency: results in hereditary angioedema, characterized by edema of the skin (especially periorbital) and mucosal surfaces

    Autoimmune Disorders

    • Basic Principles:
      • Characterized by immune-mediated damage of self tissues
      • US prevalence is 1%-2%
      • Involves loss of self-tolerance
        • Self-reactive lymphocytes are regularly generated but develop central (thymus and bone marrow) or peripheral tolerance
        • Central tolerance in the thymus leads to T-cell (thymocyte) apoptosis or generation of regulatory T cells
        • Central tolerance in the bone marrow leads to receptor editing or B-cell apoptosis
        • Peripheral tolerance leads to anergy or apoptosis of T and B cells
        • Regulatory T cells suppress autoimmunity by blocking T-cell activation and producing anti-inflammatory cytokines (IL-10 and TGF-β)
      • More common in women; classically affects women of childbearing age
      • Etiology is likely an environmental trigger in genetically-susceptible individuals
        • Increased incidence in twins

    Fundamentals of Pathology

    • Macrophages process and present antigens via MHC class II to CD4+ helper T cells.
    • Macrophages secrete IL-12 after interacting with helper T cells.
    • IL-12 causes helper T cells to differentiate into T H1 subtype.
    • TH1 cells secrete IFN-γ, which converts macrophages into epithelioid histiocytes and giant cells.

    Primary Immunodeficiency

    • DiGeorge Syndrome:

      • Developmental failure of the third and fourth pharyngeal pouches.
      • Caused by 22q11 microdeletion.
      • Presents with T-cell deficiency, hypocalcemia, and abnormalities of the heart, great vessels, and face.

    • Severe Combined Immunodeficiency (SCID):

      • Defective cell-mediated and humoral immunity.
      • Etiologies involve:
        • Cytokine receptor defects.
        • Adenosine deaminase (ADA) deficiency.
        • MHC class II deficiency.
      • Characterized by susceptibility to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines.
      • Treatment involves sterile isolation and stem cell transplantation.

    • X-Linked Agammaglobulinemia:

      • Complete lack of immunoglobulin due to disordered B-cell maturation.
      • Caused by a mutated Bruton tyrosine kinase, which is X-linked.
      • Presents after six months of life with recurrent bacterial, enterovirus, and Giardia lamblia infections.
      • Maternal antibodies present during the first six months of life provide protection.
      • Live vaccines must be avoided.

    • Common Variable Immunodeficiency (CVID):

      • Low immunoglobulin due to B-cell or helper T-cell defects.
      • Increased risk of bacterial, enterovirus, and Giardia lamblia infections, usually in late childhood.
      • Increased risk of autoimmune disease and lymphoma.

    • IgA Deficiency:

      • Low serum and mucosal IgA, the most common immunoglobulin deficiency.
      • Increased risk of mucosal infection, especially viral; however, most patients are asymptomatic.

    • Hyper-IgM Syndrome:

      • Characterized by elevated IgM.
      • Caused by a mutated CD40L (on helper T cells) or CD40 receptor (on B cells).
      • Impaired delivery of the second signal to helper T cells during B-cell activation.
      • Deficiency in IgA, IgG, and IgE, leading to recurrent pyogenic infections 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, which is X-linked.
      • Bleeding is a major cause of death.

    • Complement Deficiencies:

      • C5-C9 deficiencies increase the risk of Neisseria infection (N gonorrhoeae and N meningitidis).
      • C1 inhibitor deficiency leads to hereditary angioedema, characterized by edema of the skin and mucosal surfaces.

    Autoimmune Disorders

    • Basic Principles:

      • Characterized by immune-mediated damage to self tissues.
      • Involves loss of self-tolerance.
      • More common in women, especially of childbearing age.
      • Etiology likely involves an environmental trigger in genetically susceptible individuals.

    • Loss of Self-Tolerance:

      • Self-reactive lymphocytes are regularly generated but become tolerant in the thymus or bone marrow.
      • Central Tolerance:
        • Central tolerance in the thymus leads to T-cell apoptosis or the generation of regulatory T cells.
        • AIRE mutations result in autoimmune polyendocrine syndrome.
        • Central tolerance in the bone marrow leads to receptor editing or B-cell apoptosis.
      • Peripheral Tolerance:
        • Peripheral tolerance leads to anergy or apoptosis of T and B cells.
        • Fas apoptosis pathway mutations result in autoimmune lymphoproliferative syndrome (ALPS).
        • Regulatory T cells suppress autoimmunity by blocking T-cell activation and producing anti-inflammatory cytokines.
        • CD25 polymorphisms are associated with autoimmunity (MS and type 1DM)
        • FOXP3 mutations lead to IPEX syndrome.

    Fundamentals of Pathology

    • Macrophages process and present antigens to CD4+ helper T cells via MHC class II
    • Helper T cells release IL-12, which induces differentiation into TH1 subtype
    • TH1 cells secrete IFN-γ, which converts macrophages to epithelioid histiocytes and giant cells
    • Giant cells can be found in granulomas, a hallmark of many inflammatory and infectious diseases

    Primary Immunodeficiency

    • DiGeorge Syndrome:

      • Developmental failure of the third and fourth pharyngeal pouches
      • Caused by 22q11 microdeletion
      • Characterized by T-cell deficiency, hypocalcemia, and abnormalities of heart, great vessels, and face.

    • Severe Combined Immunodeficiency (SCID):

      • Defective cell-mediated and humoral immunity
      • Caused by:
        • Cytokine receptor defects: Cytokine signaling is essential for B and T cell proliferation and maturation
        • Adenosine deaminase (ADA) deficiency: Buildup of adenosine and deoxyadenosine is toxic to lymphocytes
        • MHC class II deficiency: Essential for CD4+ helper T cell activation and cytokine production
      • Characterized by susceptibility to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines
      • Treated with sterile isolation and stem cell transplantation

    • X-Linked Agammaglobulinemia:

      • Complete lack of immunoglobulin due to disordered B-cell maturation
      • Caused by mutated Bruton tyrosine kinase; X-linked
      • Presents after 6 months of age with recurrent bacterial, enterovirus, and Giardia lamblia infections
      • Maternal antibodies provide protection during the first 6 months of life, but live vaccines must be avoided

    • Common Variable Immunodeficiency (CVID):

      • Low immunoglobulin levels due to B-cell or helper T-cell defects
      • Increased risk for bacterial, enterovirus, and Giardia lamblia infections, typically in late childhood
      • Increased risk of autoimmune disease and lymphoma

    • IgA Deficiency:

      • Most common immunoglobulin deficiency, characterized by low serum and mucosal IgA
      • Increased risk for mucosal infections, primarily viral, but 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)
      • The second signal necessary for B-cell activation cannot be delivered to helper T cells.
      • Low IgA, IgG, and IgE result in recurrent pyogenic infections, especially at mucosal sites

    • Wiskott-Aldrich Syndrome:

      • Characterized by thrombocytopenia, eczema, and recurrent infections (defective humoral and cellular immunity)
      • Caused by mutations in the WASP gene; X-linked
      • Bleeding is a major cause of death

    • Complement Deficiencies:

      • C5-C9 deficiencies: Increased risk for Neisseria infection (N. gonorrhoeae and N. meningitidis)
      • C1 inhibitor deficiency: Hereditary angioedema: Edema of the skin (especially periorbital) and mucosal surfaces

    Autoimmune Disorders

    • Characterized by immune-mediated damage to self tissues, affecting 1%-2% of the US population.
    • Loss of self-tolerance:
      • Self-reactive lymphocytes are regularly generated but develop central (thymus and bone marrow) or peripheral tolerance
      • Central tolerance in thymus: T-cell apoptosis or generation of regulatory T cells
        • AIRE mutations cause autoimmune polyendocrine syndrome.
      • Central tolerance in 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:
        • Blocking T-cell activation and producing anti-inflammatory cytokines (IL-10 and TGF-β)
        • CD25 polymorphisms are associated with autoimmune diseases (MS and type 1DM)
        • FOXP3 mutations cause IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked).
    • More common in women, particularly those of childbearing age.
    • Etiology: Environmental triggers in genetically-susceptible individuals.
      • Increased incidence among twins

    Fundamentals of Pathology

    • Macrophages process and present antigen via MHC class II to CD4+ helper T cells.
    • Interaction leads macrophages to secrete IL-12, inducing CD4+ helper T cells to differentiate into TH1 subtype.
    • TH1 cells secrete IFN-γ, which converts macrophages to epithelioid histiocytes and giant cells.

    Primary Immunodeficiency

    • DiGeorge Syndrome

      • Developmental failure of the third and fourth pharyngeal pouches
        • Due to 22q11 microdeletion
      • Presents with T-cell deficiency (lack of thymus); hypocalcemia (lack of parathyroids); and abnormalities of heart, great vessels, and face.

    • Severe Combined Immunodeficiency (SCID)

      • Defective cell-mediated and humoral immunity
      • Etiologies include
        • Cytokine receptor defects - Cytokine signaling is necessary for proliferation and maturation of B and T cells.
        • Adenosine deaminase (ADA) deficiency - ADA is necessary to deaminate adenosine and deoxyadenosine for excretion as waste products; buildup of adenosine and deoxyadenosine is toxic to lymphocytes.
        • MHC class II deficiency - MHC class II is necessary for CD4+ helper T cell activation and cytokine production.
      • Characterized by susceptibility to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines
      • Treatment is sterile isolation ('bubble baby') and stem cell transplantation.

    • X-Linked Agammaglobulinemia

      • Complete lack of immunoglobulin due to disordered B-cell maturation
        • Pre- and pro-B cells cannot mature.
      • Due to mutated Bruton tyrosine kinase; X-linked
      • Presents after 6 months of life with recurrent bacterial, enterovirus (e.g., polio and coxsackievirus), and Giardia lamblia infections; maternal antibodies present during the first 6 months of life are protective.
      • Live vaccines (e.g., polio) must be avoided.

    • Common Variable Immunodeficiency (CVID)

      • Low immunoglobulin due to B-cell or helper T-cell defects
      • Increased risk for bacterial, enterovirus, and Giardia lamblia infections, usually in late childhood
      • Increased risk for autoimmune disease and lymphoma

    • IgA Deficiency

      • Low serum and mucosal IgA; most common immunoglobulin deficiency
      • Increased risk for mucosal infection, especially viral; however, most patients are asymptomatic.

    • Hyper-IgM Syndrome

      • Characterized by elevated IgM
      • Due to mutated CD40L (on helper T cells) or CD40 receptor (on B cells)
        • Second signal cannot be delivered to helper T cells during B-cell activation.
        • Consequently, cytokines necessary for immunoglobulin class switching are not produced.
      • Low IgA, IgG, and IgE result in 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); bleeding is a major cause of death
      • Due to mutation in the WASP gene; X-linked

    • Complement Deficiencies

      • C5-C9 deficiencies - increased risk for Neisseria infection (N gonorrhoeae and N meningitidis)
      • Cl inhibitor deficiency - results in hereditary angioedema, which is characterized by edema of the skin (especially periorbital) and mucosal surfaces

    Autoimmune Disorders

    • Characterized by immune-mediated damage of self tissues
      • US prevalence is 1%-2%.
    • Involves loss of self-tolerance
      • Self-reactive lymphocytes are regularly generated but develop central (thymus and bone marrow) or peripheral tolerance.
      • Central tolerance in thymus leads to T-cell (thymocyte) apoptosis or generation of regulatory T cells.
        • AIRE mutations result in autoimmune polyendocrine syndrome.
      • Central tolerance in bone marrow leads to receptor editing or B-cell apoptosis.
      • Peripheral tolerance leads to anergy or apoptosis of T and B cells.
        • Fas apoptosis pathway mutations result in 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 are associated with autoimmunity (MS and type 1DM).
        • FOXP3 mutations lead to IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked).
    • More common in women; classically affects women of childbearing age
      • Estrogen may reduce apoptosis of self-reactive B cells.
    • Etiology is likely an environmental trigger in genetically-susceptible individuals.
      • Increased incidence in twins

    Inflammation, Inflammatory Disorders, and Wound Healing

    • Granuloma
      • Noncaseating
      • Caseating
    • Angioedema
      • Edema of the skin (especially periorbital) and mucosal surfaces

    Fundamentals of Pathology

    • Macrophages process and present antigens through MHC class II to CD4+ helper T cells
    • Macrophages secrete IL-12, inducing CD4+ helper T cells to become T H1 subtype
    • TH1 cells secrete IFN- γ, which causes macrophages to turn into epithelioid histiocytes and giant cells

    Primary Immunodeficiency

    • DiGeorge Syndrome

      • Developmental failure of the 3rd and 4th pharyngeal pouches
      • Caused by a 22q11 microdeletion
      • Presents with T-cell deficiency, hypocalcemia, heart, great vessel, and facial abnormalities

    • Severe Combined Immunodeficiency (SCID)

      • Defective cell-mediated and humoral immunity
      • Cytokine receptor defects lead to impaired B and T cell proliferation and maturation
      • Adenosine deaminase (ADA) deficiency leads to toxic buildup of adenosine and deoxyadenosine, harming lymphocytes
      • MHC class II deficiency impairs CD4+ helper T cell activation and cytokine production
      • Patients are susceptible to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines
      • Treatment involves sterile isolation and stem cell transplantation

    • X-linked Agammaglobulinemia

      • Complete lack of immunoglobulin due to disordered B-cell maturation
      • Caused by a mutated Bruton tyrosine kinase; X-linked
      • Presents after 6 months of age with recurrent bacterial, enterovirus, and Giardia lamblia infections
      • Maternal antibodies provide protection during the first 6 months of life
      • Live vaccines must be avoided

    • Common Variable Immunodeficiency (CVID)

      • Low immunoglobulin due to B-cell or helper T-cell defects
      • Increased risk for bacterial, enterovirus, and Giardia lamblia infections, usually in late childhood
      • Increased risk for autoimmune disease and lymphoma

    • IgA Deficiency

      • Low serum and mucosal IgA; most common immunoglobulin deficiency
      • Increased risk for mucosal infection, especially viral; however, most patients are asymptomatic

    • Hyper-IgM Syndrome

      • Elevated IgM levels
      • Caused by a mutated CD40 ligand (on helper T cells) or CD40 receptor (on B cells)
      • Impairs the second signal during B-cell activation, preventing cytokine production for immunoglobulin class switching
      • Low IgA, IgG, and IgE lead to recurrent pyogenic infections, especially at mucosal sites

    • Wiskott-Aldrich Syndrome

      • Thrombocytopenia, eczema, and recurrent infections due to defective humoral and cellular immunity; bleeding is a major hazard
      • Caused by a mutation in the WASP gene; X-linked

    • Complement Deficiencies

      • C5-C9 deficiencies: Increased risk for Neisseria infections (N gonorrhoeae and N meningitidis)
      • C1 inhibitor deficiency: Results in hereditary angioedema, characterized by edema of the skin (especially periorbital) and mucosal surfaces

    Autoimmune Disorders

    • Characterized by immune-mediated damage of self tissues
    • US prevalence is 1%-2%
    • Involves the loss of self-tolerance
      • Self-reactive lymphocytes undergo central (thymus and bone marrow) or peripheral tolerance mechanisms
      • Central tolerance:
        • In the thymus: Leads to T cell (thymocyte) apoptosis or development of regulatory T cells
          • AIRE mutations result in autoimmune polyendocrine syndrome
        • In the bone marrow: Leads to receptor editing or B cell apoptosis
      • Peripheral tolerance: Leads to anergy or apoptosis of T and B cells
        • Fas apoptosis pathway mutations result in 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 are associated with autoimmunity (MS and type 1 diabetes mellitus)
        • FOXP3 mutations lead to IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked)
    • More common in women; classically affects those of childbearing age
      • Estrogen may reduce apoptosis of self-reactive B cells
    • Etiology likely involves environmental triggers in genetically susceptible individuals
      • Increased incidence in twins

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    Description

    This quiz covers crucial concepts in pathology, focusing on the role of macrophages and T cells in immune responses. It also explores specific primary immunodeficiencies such as DiGeorge Syndrome and Severe Combined Immunodeficiency, detailing their mechanisms and clinical presentations.

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