Immunology Chapter on Leukocyte Function
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Questions and Answers

What is the primary mechanism by which phagocytosed material is destroyed in leukocytes?

  • O2-independent killing
  • O2-dependent killing (correct)
  • Endocytosis
  • Apoptosis

    • In chronic granulomatous disease (CGD), what is the primary defect?

  • Superoxide dismutase deficiency
  • Impaired phagocytosis
  • NADPH oxidase defect (correct)
  • Myeloperoxidase deficiency

    • Which organisms are particularly associated with recurrent infections in chronic granulomatous disease?

  • Fungi only
  • Viral pathogens
  • Gram-negative bacilli
  • Catalase-positive organisms (correct)

    • What is the result of an MPO deficiency in a patient?

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

    What role do opsonins play in phagocytosis?

    <p>They enhance the recognition and ingestion of pathogens.</p> Signup and view all the answers

    Which outcome is NOT associated with macrophage activity during inflammation?

    <p>Depletion of lymphocytes in chronic inflammation.</p> Signup and view all the answers

    What indicates a positive Nitroblue tetrazolium (NBT) test?

    <p>Leukocytes turn blue</p> Signup and view all the answers

    What role do neutrophils play following the resolution of inflammation?

    <p>They undergo apoptosis and disappear</p> Signup and view all the answers

    Which of the following is a characteristic of chronic inflammation?

    <p>Involvement of lymphocytes and plasma cells in tissue.</p> Signup and view all the answers

    What is the primary role of CD4+ helper T cells in chronic inflammation?

    <p>Secreting cytokines that promote chronic inflammation.</p> Signup and view all the answers

    Which of the following describes the sequence by which macrophages arrive in tissues?

    <p>Rolling, margination, adhesion, transmigration</p> Signup and view all the answers

    What is the role of myeloperoxidase in the leukocyte oxidative burst?

    <p>Generation of HOCl from hydrogen peroxide</p> Signup and view all the answers

    Which stimuli is most commonly associated with triggering chronic inflammation?

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

    What is the primary role of pyrogens such as LPS in fever development?

    <p>They cause macrophages to release IL-1 and TNF.</p> Signup and view all the answers

    Which cell adhesion molecules are primarily upregulated on the endothelium by TNF and IL-1?

    <p>ICAM and VCAM</p> Signup and view all the answers

    What induces the expression of E-selectin on endothelial cells?

    <p>TNF and IL-1</p> Signup and view all the answers

    What condition is characterized by delayed separation of the umbilical cord and recurrent bacterial infections due to leukocyte adhesion issues?

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

    What is the initial step of neutrophil recruitment during inflammation termed?

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

    What enhances phagocytosis in leukocytes?

    <p>Opsonins such as IgG and C3b</p> Signup and view all the answers

    Which of the following substances attract neutrophils during inflammation?

    <p>C5a, LTB4, and bacterial products</p> Signup and view all the answers

    What is a clinical feature of Chediak-Higashi syndrome?

    <p>Neutropenia due to intramedullary death</p> Signup and view all the answers

    Chronic inflammation is primarily characterized by the presence of neutrophils and fibroblasts in tissue.

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

    The production of anti-inflammatory cytokines by macrophages contributes to the resolution and healing of inflammation.

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

    T cells differentiate into CD4+ helper T cells in the bone marrow.

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

    Chronic inflammation often results from autoimmune diseases and persistent infections.

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

    The T-cell receptor (TCR) undergoes rearrangement solely in the bone marrow.

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

    IL-1 and TNF increase cyclooxygenase activity in perivascular cells of the hypothalamus, causing fever.

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

    Vasoconstriction in postcapillary venules facilitates leukocyte margination by speeding up blood flow.

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

    Selectins facilitate the rolling of leukocytes by interacting with sialyl Lewis X.

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

    Integrins are upregulated on leukocytes in response to histamine.

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

    Phagocytosis is enhanced by opsonins like IgG and C3a.

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

    Chediak-Higashi syndrome is characterized by impaired phagolysosome formation due to a dominant genetic defect.

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

    Neutrophils are attracted to sites of infection by products such as IL-8 and C5a.

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

    Leukocyte adhesion deficiency primarily results from a defect in the CD4 subunit of integrins.

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

    Chronic granulomatous disease (CGD) is caused by a defect in the NADPH oxidase enzyme, leading to ineffective O2-dependent killing.

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

    Myeloperoxidase (MPO) deficiency results in an increased conversion of H2O2 to HOCl and a significantly higher risk for Candida infections.

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

    O2-independent killing mechanisms by leukocytes are generally more effective than O2-dependent killing mechanisms.

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

    The Nitroblue tetrazolium (NBT) test becomes colorless if NADPH oxidase functions correctly.

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

    Macrophages typically peak in number a few hours after the onset of inflammation.

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

    Catalase-positive organisms are more likely to cause infections in individuals with chronic granulomatous disease (CGD).

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

    The primary way leukocytes destroy phagocytosed material is through the production of hydrochloric acid (HCl).

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

    Neutrophils typically undergo apoptosis and clear from the site of inflammation within 48 hours of resolution.

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

    How do macrophages manage the inflammatory process to promote resolution and healing?

    <p>Macrophages produce anti-inflammatory cytokines such as IL-10 and TGF-β to facilitate resolution and healing of inflammation.</p> Signup and view all the answers

    What characterizes chronic inflammation compared to acute inflammation?

    <p>Chronic inflammation is marked by a delayed response involving lymphocytes and plasma cells, and it is often more specific due to adaptive immunity.</p> Signup and view all the answers

    What underlying mechanisms can lead to the formation of an abscess during inflammation?

    <p>An abscess forms due to acute inflammation that becomes encapsulated by fibrosis, mediated by macrophages through fibrogenic growth factors and cytokines.</p> Signup and view all the answers

    Describe the role of T lymphocytes in chronic inflammation.

    <p>T lymphocytes, particularly CD4+ helper T cells, present antigens and secrete cytokines that promote and sustain chronic inflammation.</p> Signup and view all the answers

    What are the common stimuli that can initiate chronic inflammation?

    <p>Chronic inflammation can be initiated by persistent infections, autoimmune diseases, foreign material, and certain cancers.</p> Signup and view all the answers

    What role do pyrogens play in the development of fever?

    <p>Pyrogens stimulate macrophages to release IL-1 and TNF, which elevate the temperature set point in the hypothalamus.</p> Signup and view all the answers

    Describe how rolling of leukocytes occurs during inflammation.

    <p>Leukocytes roll along the vessel wall due to selectins on endothelial cells binding to sialyl Lewis X on leukocytes.</p> Signup and view all the answers

    What is the consequence of integrin defects in leukocyte adhesion deficiency?

    <p>Integrin defects lead to impaired adhesion of leukocytes, resulting in delayed umbilical cord separation and recurrent infections.</p> Signup and view all the answers

    Explain the significance of chemotaxis in leukocyte function.

    <p>Chemotaxis directs leukocytes toward sites of infection through chemical signals, such as IL-8 and C5a.</p> Signup and view all the answers

    What distinguishes Chediak-Higashi syndrome from other immune disorders?

    <p>Chediak-Higashi syndrome is marked by impaired phagolysosome formation and results in increased susceptibility to pyogenic infections.</p> Signup and view all the answers

    How does vasodilation facilitate neutrophil margination?

    <p>Vasodilation slows blood flow in postcapillary venules, allowing leukocytes to marginate to the periphery of the vessel.</p> Signup and view all the answers

    What is the relationship between opsonins and phagocytosis?

    <p>Opsonins like IgG and C3b enhance phagocytosis by marking pathogens for recognition and ingestion by leukocytes.</p> Signup and view all the answers

    In what way do bacterial products influence neutrophil behavior?

    <p>Bacterial products serve as chemotactic signals that attract neutrophils to the site of infection.</p> Signup and view all the answers

    What defect characterizes Chronic Granulomatous Disease (CGD) regarding its effect on immune response?

    <p>A defect in the NADPH oxidase enzyme impairs O2-dependent killing.</p> Signup and view all the answers

    How do neutrophils contribute to the resolution of inflammation after the inflammatory stimulus is removed?

    <p>Neutrophils undergo apoptosis and disappear within 24 hours.</p> Signup and view all the answers

    What is the role of superoxide dismutase (SOD) in the oxidative burst mechanism?

    <p>SOD converts O2ꜙ into H2O2 during the respiratory burst.</p> Signup and view all the answers

    What type of organisms are individuals with Chronic Granulomatous Disease particularly susceptible to?

    <p>Individuals are particularly susceptible to catalase-positive organisms such as Staphylococcus aureus.</p> Signup and view all the answers

    What test is used to screen for defects in NADPH oxidase and how does it indicate the defect?

    <p>The Nitroblue tetrazolium (NBT) test is used; it turns blue if NADPH oxidase is functioning.</p> Signup and view all the answers

    What role does myeloperoxidase (MPO) play in the process of phagocytosis?

    <p>MPO converts H2O2 to HOCl, which is crucial for killing ingested microbes.</p> Signup and view all the answers

    Describe the significance of O2-independent killing mechanisms in leukocyte function.

    <p>O2-independent mechanisms, though less effective, utilize enzymes in secondary granules for microbial killing.</p> Signup and view all the answers

    How does peripheral neuropathy relate to the deficiencies observed in certain leukocyte functions?

    <p>Defective hemostasis and abnormal granules in leukocytes may contribute to inflammatory responses impacting nerves.</p> Signup and view all the answers

    Macrophages produce anti-inflammatory cytokines such as IL-10 and TGF-β to promote ______.

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

    Chronic inflammation is characterized by the presence of ______ and plasma cells in tissue.

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

    The rearrangement of the T-cell receptor occurs in the ______.

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

    One consequence of macrophage activity during inflammation is the formation of an ______.

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

    T cells can differentiate into either CD4+ helper T cells or CD8+ ______ T cells.

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

    Pyrogens cause macrophages to release ______ and TNF, which increase cyclooxygenase activity.

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

    Chronic granulomatous disease (CGD) is characterized by poor O2-dependent killing due to a defect in ______.

    <p>NADPH oxidase</p> Signup and view all the answers

    Selectin 'speed bumps' are upregulated on endothelial cells by ______.

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

    The ______ tetrazolium test is used to screen for chronic granulomatous disease.

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

    Cellular adhesion molecules such as ICAM and VCAM are upregulated by ______ and IL-1.

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

    MPO deficiency results in a defect in the conversion of H2O2 to ______.

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

    Leukocyte adhesion deficiency is commonly due to a defect in the ______ subunit of integrins.

    <p>CD18</p> Signup and view all the answers

    Neutrophils are attracted by bacterial products, IL-8, C5a, and ______.

    <p>LTB4</p> Signup and view all the answers

    Patients with MPO deficiency are at increased risk for ______ infections.

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

    Phagocytosis is enhanced by ______ such as IgG and C3b.

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

    O2-independent killing by leukocytes is generally ______ effective than O2-dependent killing.

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

    Macrophages derived from ______ in the blood predominate after neutrophils during inflammation.

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

    The Chediak-Higashi syndrome is characterized by impaired ______ formation.

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

    Transmigration of leukocytes occurs across the endothelium of ______ venules.

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

    Granuloma formation in CGD is primarily associated with catalase-______ organisms.

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

    O2 is converted to O2ꜙ by the enzyme ______ during the oxidative burst.

    <p>NADPH oxidase</p> Signup and view all the answers

    Match the types of inflammation outcomes with their corresponding descriptions:

    <p>Resolution and healing = Production of anti-inflammatory cytokines like IL-10 Continued acute inflammation = Marked by persistent pus formation and recruitment of neutrophils Abscess = Acute inflammation surrounded by fibrosis Chronic inflammation = Characterized by the presence of lymphocytes and plasma cells</p> Signup and view all the answers

    Match the stimuli for chronic inflammation with their corresponding descriptions:

    <p>Persistent infection = Most common cause leading to chronic inflammation Autoimmune disease = Results from an inappropriate immune response against self Infection with viruses = Includes mycobacteria, parasites, and fungi Foreign material = Tissue response to substances that are not self</p> Signup and view all the answers

    Match the types of T cells with their functions:

    <p>Progenitor T cells = Produced in the bone marrow and not yet differentiated T cells = Use TCR complex for antigen surveillance CD4+ helper T cells = Activate other immune cells and secrete cytokines CD8+ cytotoxic T cells = Directly kill infected or cancerous cells</p> Signup and view all the answers

    Match the outcomes of macrophage activity with their descriptions:

    <p>Resolution and healing = Involves production of anti-inflammatory cytokines Pus formation = Indicates ongoing acute inflammation and neutrophil recruitment Fibrosis = Mediated by macrophages through fibrogenic factors and cytokines Antigen presentation = Activates CD4+ helper T cells for chronic inflammation</p> Signup and view all the answers

    Match the phases of T lymphocyte development with their processes:

    <p>Bone marrow = Site of progenitor T cell production Thymus = Where TCR undergoes rearrangement Activation = Involves interactions with antigen-presenting cells Differentiation = Results in formation of CD4+ and CD8+ T cells</p> Signup and view all the answers

    Match the following conditions with their associated characteristics:

    <p>Chronic Granulomatous Disease (CGD) = NADPH oxidase defect leading to recurrent infections MPO Deficiency = Defective conversion of H2O2 to HOCl Albinism = Absence of melanin pigment Peripheral Neuropathy = Damage to the peripheral nervous system</p> Signup and view all the answers

    Match the following components of the oxidative burst with their respective roles:

    <p>NADPH oxidase = Converts O2 to O2ꜙ Superoxide dismutase (SOD) = Converts O2ꜙ to H2O2 Myeloperoxidase (MPO) = Converts H2O2 to HOCl Lysozyme in macrophages = Partakes in O2-independent killing</p> Signup and view all the answers

    Match the following test results with their respective conditions:

    <p>Positive Nitroblue tetrazolium (NBT) test = Functional NADPH oxidase Normal NBT test in MPO deficiency = Intact respiratory burst Colorless NBT test in CGD = NADPH oxidase defect Normal respiratory burst = MPO deficiency</p> Signup and view all the answers

    Match the following organisms with their relevance to CGD:

    <p>Staphylococcus aureus = Catalase-positive organism associated with infections Pseudomonas cepacia = Recurrent infections in CGD patients Serratia marcescens = Associated with granuloma formation in CGD Aspergillus = Known to cause infections in CGD patients</p> Signup and view all the answers

    Match the phase of phagocytosis with its description:

    <p>O2-dependent killing = Most effective mechanism in leukocytes O2-independent killing = Involves enzymes from leukocyte secondary granules Apoptosis of neutrophils = Occurs within 24 hours post-inflammation Macrophages' peak presence = 2-3 days after inflammation starts</p> Signup and view all the answers

    Match the following elements of inflammation with their functions:

    <p>Neutrophils = First responders in inflammation Macrophages = Predominate after neutrophils during inflammation Oxidative burst = Mechanism of phagocytosed material destruction Granules in leukocytes = Fusion product from Golgi apparatus</p> Signup and view all the answers

    Match the following terms with their definitions:

    <p>Margination = Process of leukocyte positioning along the endothelium Rolling = Initial step in leukocyte adhesion during inflammation Transmigration = Leukocytes moving through the endothelial barrier Respiratory burst = Rapid release of reactive oxygen species by leukocytes</p> Signup and view all the answers

    Match the following leukocyte characteristics with their effects:

    <p>Defective primary hemostasis = Due to dense granule abnormalities Increased risk for Candida infections = Due to MPO deficiency Recurrent infections = A hallmark of CGD Rapid disappearance = Apoptosis of neutrophils after resolution</p> Signup and view all the answers

    Match the steps of neutrophil arrival with their descriptions:

    <p>Step 2 - Rolling = Interaction results in rolling of leukocytes along the vessel wall. Step 3 - Adhesion = Integrins on leukocytes bind to cell adhesion molecules on the endothelium. Step 4 - Transmigration and Chemotaxis = Leukocytes move toward chemical attractants. Step 1 - Margination = Cells marginate from center of flow to the periphery.</p> Signup and view all the answers

    Match the clinical features of Chediak-Higashi syndrome with their descriptions:

    <p>Increased risk of pyogenic infections = Due to impaired phagolysosome formation. Neutropenia = Caused by intramedullary death of neutrophils. Delayed separation of the umbilical cord = Associated with leukocyte adhesion issues. Recurrent bacterial infections = Typically lack pus formation.</p> Signup and view all the answers

    Match the inflammatory mediators with their roles in fever development:

    <p>IL-1 = Causes macrophages to release pyrogens. TNF = Increases cyclooxygenase activity in the hypothalamus. PGE2 = Raises temperature set point. LPS = Acts as a pyrogen from bacteria.</p> Signup and view all the answers

    Match the adhesion molecules with their characteristics:

    <p>Selectins = Upregulated by histamine and TNF. Integrins = Upregulated on leukocytes by C5a and LTB4. ICAM and VCAM = Cellular adhesion molecules on endothelium. Sialyl Lewis X = Interacts with selectins on leukocytes.</p> Signup and view all the answers

    Match the steps of phagocytosis with their processes:

    <p>Pseudopod extension = Forms phagosomes. Phagosomes merging with lysosomes = Produces phagolysosomes. Opsonins = Enhance phagocytosis. Consumption of pathogens = Describes the overall goal of phagocytosis.</p> Signup and view all the answers

    Match the leukocyte recruitment steps with their processes:

    <p>Margination = Slowing of blood flow in postcapillary venules. Rolling = Involves selectin-mediated interactions. Adhesion = Firm binding of leukocytes to the vessel wall. Transmigration = Movement of leukocytes across endothelium.</p> Signup and view all the answers

    Match the conditions or features with their associated mechanisms:

    <p>Leukocyte Adhesion Deficiency = Due to defect in integrins (CD18 subunit). Chronic Granulomatous Disease = Caused by NADPH oxidase defect. Chediak-Higashi Syndrome = Characterized by protein trafficking defects. Neutrophil apoptosis = Typically occurs within 48 hours of resolution.</p> Signup and view all the answers

    Match the cytokines with their functions in inflammation:

    <p>IL-8 = Attracts neutrophils. C5a = Acts as a potent chemotactic factor. TNF = Induces E-selectin expression on endothelium. IL-1 = Increases endothelial adhesion molecule expression.</p> Signup and view all the answers

    Study Notes

    Inflammation

    • Inflammation is a complex response to tissue injury and infection. It results in the rapid vascular and cellular response to eliminate and contain the injury agent, thereby initiating the healing process.
    • Key hallmarks of inflammation include rubor (redness), calor (heat), tumor (swelling), dolor (pain), and functio laesa (loss of function).

    Fever

    • Fever is a systemic manifestation of inflammation.
    • Pyrogens, like bacterial LPS, stimulate macrophages to release IL-1 and TNF.
    • These cytokines increase cyclooxygenase activity in the hypothalamus, leading to increased PGE2 production.
    • PGE2 raises the hypothalamic thermostat, causing an elevation in body temperature.

    Neutrophil Arrival and Function

    • Neutrophils are the first responders to inflammation and arrive at the site of injury within hours.
    • Margination: As vasodilation occurs, blood flow slows in postcapillary venules, allowing neutrophils to move to the periphery of the vessel.
    • Rolling: Selectins, upregulated on endothelial cells, bind to sialyl Lewis X on neutrophils, facilitating their rolling action along the vessel wall.
    • Adhesion: Cellular adhesion molecules (ICAM and VCAM), upregulated on endothelium, bind to integrins, upregulated on neutrophils, leading to strong adhesion of neutrophils to the vessel wall.
    • Transmigration/Chemotaxis: Neutrophils transmigrate across the endothelium and move toward chemical attractants like bacterial products, IL-8, C5a, and LTB4.
    • Phagocytosis: Neutrophils engulf pathogens and necrotic tissue, a process enhanced by opsonins (IgG and C3b).
    • Destruction: Neutrophils destroy phagocytosed material, primarily through oxygen-dependent killing.
    • Resolution: Neutrophils undergo apoptosis within 24 hours after resolution of the inflammatory stimulus.

    Macrophages

    • Macrophages dominate the inflammatory response after neutrophils, peaking 2-3 days after inflammation begins.
    • Macrophages arrive via the same margination, rolling, adhesion, and transmigration sequence as neutrophils.
    • They ingest organisms via phagocytosis and destroy phagocytosed material using enzymes in secondary granules (oxygen-independent killing).
    • Macrophages decide the next step in the inflammatory process, determining whether the outcome will be resolution and healing, continued acute inflammation, abscess formation, or chronic inflammation.

    Chronic Inflammation

    • Chronic inflammation is characterized by the presence of lymphocytes and plasma cells in tissue.
    • Chronic inflammation is a delayed, more specific (adaptive immunity) response compared to acute inflammation.
    • Common stimuli for chronic inflammation include persistent infections, infections with viruses, mycobacteria, parasites, and fungi, autoimmune disease, foreign material, and some cancers.

    T Lymphocytes

    • T lymphocytes originate in the bone marrow as progenitor T cells.
    • They further differentiate in the thymus, where they undergo T cell receptor (TCR) rearrangement and become CD4+ helper T cells or CD8+ cytotoxic T cells.
    • T cells use the TCR complex (TCR and CD3) for antigen surveillance.

    Fever

    • Pyrogens (e.g., LPS from bacteria) trigger macrophages to release IL-1 and TNF, which increase cyclooxygenase activity in perivascular cells of the hypothalamus.
    • Increased PGE2 elevates the temperature set point.

    Neutrophil Arrival and Function

    Margination

    • Vasodilation slows blood flow in postcapillary venules.
    • Cells marginate from the center of the blood flow to the periphery.

    Rolling

    • Selectin "speed bumps" are upregulated on endothelial cells.
      • P-selectin release from Weibel-Palade bodies is mediated by histamine.
      • E-selectin is induced by TNF and IL-1.
    • Selectins bind sialyl Lewis X on leukocytes.
    • This interaction results in leukocytes rolling along the vessel wall.

    Adhesion

    • Cellular adhesion molecules (ICAM and VCAM) are upregulated on endothelium by TNF and IL-1.
    • Integrins are upregulated on leukocytes by C5a and LTB4.
    • The interaction between CAMs and integrins leads to firm adhesion of leukocytes to the vessel wall.
    • Leukocyte adhesion deficiency is often caused by an autosomal recessive defect of integrins (CD18 subunit).
      • This results in delayed separation of the umbilical cord, increased circulating neutrophils (due to impaired adhesion of marginated leukocytes), and recurrent bacterial infections that lack pus formation.

    Transmigration and Chemotaxis

    • Leukocytes transmigrate across the postcapillary venule endothelium and move toward chemical attractants (chemotaxis).
    • Neutrophils are attracted by bacterial products, IL-8, C5a, and LTB4.

    Phagocytosis

    • Consumption of pathogens or necrotic tissue; phagocytosis is enhanced by opsonins (IgG and C3b).
    • Pseudopods extend from leukocytes to form phagosomes, which are internalized and merge with lysosomes to produce phagolysosomes.
    • Chediak-Higashi syndrome is an autosomal recessive protein trafficking defect characterized by impaired phagolysosome formation. Clinical features include:
      • Increased risk of pyogenic infections
      • Neutropenia (due to intramedullary death of neutrophils)
      • Giant granules in leukocytes (due to fusion of granules arising from the Golgi apparatus)
      • Defective primary hemostasis (due to abnormal dense granules in platelets)
      • Albinism
      • Peripheral neuropathy

    Destruction of Phagocytosed Material

    • O2-dependent killing is the most effective mechanism.
    • HOCl generated by the oxidative burst in phagolysosomes destroys phagocytosed microbes.
      • O2 is converted to O2ꜙ by NADPH oxidase (oxidative burst).
      • O2ꜙ is converted to H2O2 by superoxide dismutase (SOD).
      • H2O2 is converted to HOCl (bleach) by myeloperoxidase (MPO).
    • Chronic granulomatous disease (CGD) is characterized by poor O2-dependent killing.
      • Due to NADPH oxidase defect (X-linked or autosomal recessive)
      • Leads to recurrent infection and granuloma formation with catalase-positive organisms, particularly Staphylococcus aureus, Pseudomonas cepacia, Serratia marcescens, Nocardia, and Aspergillus.
      • Nitroblue tetrazolium test is used to screen for CGD.
        • Leukocytes are incubated with NBT dye, which turns blue if NADPH oxidase can convert O2 to O2ꜙ, but remains colorless if NADPH oxidase is defective.
    • MPO deficiency results in defective conversion of H2O2 to HOCl.
      • Increased risk for Candida infections, however, most patients are asymptomatic.
      • NBT is normal; respiratory burst (O2 to H2O2) is intact.
    • O2-independent killing is less effective than O2-dependent killing and occurs via enzymes present in leukocyte secondary granules (e.g., lysozyme in macrophages and major basic protein in eosinophils).

    Resolution

    • Neutrophils undergo apoptosis and disappear within 24 hours after resolution of the inflammatory stimulus.

    Macrophages

    • Macrophages predominate after neutrophils and peak 2-3 days after inflammation begins.
    • Derived from monocytes in blood.
    • Arrive in tissue via the margination, rolling, adhesion, and transmigration sequence.
    • Ingest organisms via phagocytosis (augmented by opsonins) and destroy phagocytosed material using enzymes (e.g., lysozyme) in secondary granules (O2- independent killing).
    • Manage the next step of the inflammatory process. Outcomes include:
      • Resolution and healing: Anti-inflammatory cytokines (e.g., IL-10 and TGF- β) are produced by macrophages.
      • Continued acute inflammation: Marked by persistent pus formation; IL-8 from macrophages recruits additional neutrophils.
      • Abscess: Acute inflammation surrounded by fibrosis; macrophages mediate fibrosis via fibrogenic growth factors and cytokines.
      • Chronic inflammation: Macrophages present antigen to activate CD4+ helper T cells, which secrete cytokines that promote chronic inflammation.

    Chronic Inflammation

    Basic Principles

    • Characterized by the presence of lymphocytes and plasma cells in tissue.
    • Delayed response, but more specific (adaptive immunity) than acute inflammation.
    • Stimuli include:
      • Persistent infection (most common cause)
      • Infection with viruses, mycobacteria, parasites, and fungi
      • Autoimmune disease
      • Foreign material
      • Some cancers

    T Lymphocytes

    • Produced in bone marrow as progenitor T cells.
    • Further develop in the thymus where the T-cell receptor (TCR) undergoes rearrangement and progenitor cells become CD4+ helper T cells or CD8+ cytotoxic T cells.
    • T cells use the TCR complex (TCR and CD3) for antigen surveillance.

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