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Questions and Answers
What is the primary mechanism by which phagocytosed material is destroyed in leukocytes?
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?
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?
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?
What is the result of an MPO deficiency in a patient?
What role do opsonins play in phagocytosis?
What role do opsonins play in phagocytosis?
Which outcome is NOT associated with macrophage activity during inflammation?
Which outcome is NOT associated with macrophage activity during inflammation?
What indicates a positive Nitroblue tetrazolium (NBT) test?
What indicates a positive Nitroblue tetrazolium (NBT) test?
What role do neutrophils play following the resolution of inflammation?
What role do neutrophils play following the resolution of inflammation?
Which of the following is a characteristic of chronic inflammation?
Which of the following is a characteristic of chronic inflammation?
What is the primary role of CD4+ helper T cells in chronic inflammation?
What is the primary role of CD4+ helper T cells in chronic inflammation?
Which of the following describes the sequence by which macrophages arrive in tissues?
Which of the following describes the sequence by which macrophages arrive in tissues?
What is the role of myeloperoxidase in the leukocyte oxidative burst?
What is the role of myeloperoxidase in the leukocyte oxidative burst?
Which stimuli is most commonly associated with triggering chronic inflammation?
Which stimuli is most commonly associated with triggering chronic inflammation?
What is the primary role of pyrogens such as LPS in fever development?
What is the primary role of pyrogens such as LPS in fever development?
Which cell adhesion molecules are primarily upregulated on the endothelium by TNF and IL-1?
Which cell adhesion molecules are primarily upregulated on the endothelium by TNF and IL-1?
What induces the expression of E-selectin on endothelial cells?
What induces the expression of E-selectin on endothelial cells?
What condition is characterized by delayed separation of the umbilical cord and recurrent bacterial infections due to leukocyte adhesion issues?
What condition is characterized by delayed separation of the umbilical cord and recurrent bacterial infections due to leukocyte adhesion issues?
What is the initial step of neutrophil recruitment during inflammation termed?
What is the initial step of neutrophil recruitment during inflammation termed?
What enhances phagocytosis in leukocytes?
What enhances phagocytosis in leukocytes?
Which of the following substances attract neutrophils during inflammation?
Which of the following substances attract neutrophils during inflammation?
What is a clinical feature of Chediak-Higashi syndrome?
What is a clinical feature of Chediak-Higashi syndrome?
Chronic inflammation is primarily characterized by the presence of neutrophils and fibroblasts in tissue.
Chronic inflammation is primarily characterized by the presence of neutrophils and fibroblasts in tissue.
The production of anti-inflammatory cytokines by macrophages contributes to the resolution and healing of inflammation.
The production of anti-inflammatory cytokines by macrophages contributes to the resolution and healing of inflammation.
T cells differentiate into CD4+ helper T cells in the bone marrow.
T cells differentiate into CD4+ helper T cells in the bone marrow.
Chronic inflammation often results from autoimmune diseases and persistent infections.
Chronic inflammation often results from autoimmune diseases and persistent infections.
The T-cell receptor (TCR) undergoes rearrangement solely in the bone marrow.
The T-cell receptor (TCR) undergoes rearrangement solely in the bone marrow.
IL-1 and TNF increase cyclooxygenase activity in perivascular cells of the hypothalamus, causing fever.
IL-1 and TNF increase cyclooxygenase activity in perivascular cells of the hypothalamus, causing fever.
Vasoconstriction in postcapillary venules facilitates leukocyte margination by speeding up blood flow.
Vasoconstriction in postcapillary venules facilitates leukocyte margination by speeding up blood flow.
Selectins facilitate the rolling of leukocytes by interacting with sialyl Lewis X.
Selectins facilitate the rolling of leukocytes by interacting with sialyl Lewis X.
Integrins are upregulated on leukocytes in response to histamine.
Integrins are upregulated on leukocytes in response to histamine.
Phagocytosis is enhanced by opsonins like IgG and C3a.
Phagocytosis is enhanced by opsonins like IgG and C3a.
Chediak-Higashi syndrome is characterized by impaired phagolysosome formation due to a dominant genetic defect.
Chediak-Higashi syndrome is characterized by impaired phagolysosome formation due to a dominant genetic defect.
Neutrophils are attracted to sites of infection by products such as IL-8 and C5a.
Neutrophils are attracted to sites of infection by products such as IL-8 and C5a.
Leukocyte adhesion deficiency primarily results from a defect in the CD4 subunit of integrins.
Leukocyte adhesion deficiency primarily results from a defect in the CD4 subunit of integrins.
Chronic granulomatous disease (CGD) is caused by a defect in the NADPH oxidase enzyme, leading to ineffective O2-dependent killing.
Chronic granulomatous disease (CGD) is caused by a defect in the NADPH oxidase enzyme, leading to ineffective O2-dependent killing.
Myeloperoxidase (MPO) deficiency results in an increased conversion of H2O2 to HOCl and a significantly higher risk for Candida infections.
Myeloperoxidase (MPO) deficiency results in an increased conversion of H2O2 to HOCl and a significantly higher risk for Candida infections.
O2-independent killing mechanisms by leukocytes are generally more effective than O2-dependent killing mechanisms.
O2-independent killing mechanisms by leukocytes are generally more effective than O2-dependent killing mechanisms.
The Nitroblue tetrazolium (NBT) test becomes colorless if NADPH oxidase functions correctly.
The Nitroblue tetrazolium (NBT) test becomes colorless if NADPH oxidase functions correctly.
Macrophages typically peak in number a few hours after the onset of inflammation.
Macrophages typically peak in number a few hours after the onset of inflammation.
Catalase-positive organisms are more likely to cause infections in individuals with chronic granulomatous disease (CGD).
Catalase-positive organisms are more likely to cause infections in individuals with chronic granulomatous disease (CGD).
The primary way leukocytes destroy phagocytosed material is through the production of hydrochloric acid (HCl).
The primary way leukocytes destroy phagocytosed material is through the production of hydrochloric acid (HCl).
Neutrophils typically undergo apoptosis and clear from the site of inflammation within 48 hours of resolution.
Neutrophils typically undergo apoptosis and clear from the site of inflammation within 48 hours of resolution.
How do macrophages manage the inflammatory process to promote resolution and healing?
How do macrophages manage the inflammatory process to promote resolution and healing?
What characterizes chronic inflammation compared to acute inflammation?
What characterizes chronic inflammation compared to acute inflammation?
What underlying mechanisms can lead to the formation of an abscess during inflammation?
What underlying mechanisms can lead to the formation of an abscess during inflammation?
Describe the role of T lymphocytes in chronic inflammation.
Describe the role of T lymphocytes in chronic inflammation.
What are the common stimuli that can initiate chronic inflammation?
What are the common stimuli that can initiate chronic inflammation?
What role do pyrogens play in the development of fever?
What role do pyrogens play in the development of fever?
Describe how rolling of leukocytes occurs during inflammation.
Describe how rolling of leukocytes occurs during inflammation.
What is the consequence of integrin defects in leukocyte adhesion deficiency?
What is the consequence of integrin defects in leukocyte adhesion deficiency?
Explain the significance of chemotaxis in leukocyte function.
Explain the significance of chemotaxis in leukocyte function.
What distinguishes Chediak-Higashi syndrome from other immune disorders?
What distinguishes Chediak-Higashi syndrome from other immune disorders?
How does vasodilation facilitate neutrophil margination?
How does vasodilation facilitate neutrophil margination?
What is the relationship between opsonins and phagocytosis?
What is the relationship between opsonins and phagocytosis?
In what way do bacterial products influence neutrophil behavior?
In what way do bacterial products influence neutrophil behavior?
What defect characterizes Chronic Granulomatous Disease (CGD) regarding its effect on immune response?
What defect characterizes Chronic Granulomatous Disease (CGD) regarding its effect on immune response?
How do neutrophils contribute to the resolution of inflammation after the inflammatory stimulus is removed?
How do neutrophils contribute to the resolution of inflammation after the inflammatory stimulus is removed?
What is the role of superoxide dismutase (SOD) in the oxidative burst mechanism?
What is the role of superoxide dismutase (SOD) in the oxidative burst mechanism?
What type of organisms are individuals with Chronic Granulomatous Disease particularly susceptible to?
What type of organisms are individuals with Chronic Granulomatous Disease particularly susceptible to?
What test is used to screen for defects in NADPH oxidase and how does it indicate the defect?
What test is used to screen for defects in NADPH oxidase and how does it indicate the defect?
What role does myeloperoxidase (MPO) play in the process of phagocytosis?
What role does myeloperoxidase (MPO) play in the process of phagocytosis?
Describe the significance of O2-independent killing mechanisms in leukocyte function.
Describe the significance of O2-independent killing mechanisms in leukocyte function.
How does peripheral neuropathy relate to the deficiencies observed in certain leukocyte functions?
How does peripheral neuropathy relate to the deficiencies observed in certain leukocyte functions?
Macrophages produce anti-inflammatory cytokines such as IL-10 and TGF-β to promote ______.
Macrophages produce anti-inflammatory cytokines such as IL-10 and TGF-β to promote ______.
Chronic inflammation is characterized by the presence of ______ and plasma cells in tissue.
Chronic inflammation is characterized by the presence of ______ and plasma cells in tissue.
The rearrangement of the T-cell receptor occurs in the ______.
The rearrangement of the T-cell receptor occurs in the ______.
One consequence of macrophage activity during inflammation is the formation of an ______.
One consequence of macrophage activity during inflammation is the formation of an ______.
T cells can differentiate into either CD4+ helper T cells or CD8+ ______ T cells.
T cells can differentiate into either CD4+ helper T cells or CD8+ ______ T cells.
Pyrogens cause macrophages to release ______ and TNF, which increase cyclooxygenase activity.
Pyrogens cause macrophages to release ______ and TNF, which increase cyclooxygenase activity.
Chronic granulomatous disease (CGD) is characterized by poor O2-dependent killing due to a defect in ______.
Chronic granulomatous disease (CGD) is characterized by poor O2-dependent killing due to a defect in ______.
Selectin 'speed bumps' are upregulated on endothelial cells by ______.
Selectin 'speed bumps' are upregulated on endothelial cells by ______.
The ______ tetrazolium test is used to screen for chronic granulomatous disease.
The ______ tetrazolium test is used to screen for chronic granulomatous disease.
Cellular adhesion molecules such as ICAM and VCAM are upregulated by ______ and IL-1.
Cellular adhesion molecules such as ICAM and VCAM are upregulated by ______ and IL-1.
MPO deficiency results in a defect in the conversion of H2O2 to ______.
MPO deficiency results in a defect in the conversion of H2O2 to ______.
Leukocyte adhesion deficiency is commonly due to a defect in the ______ subunit of integrins.
Leukocyte adhesion deficiency is commonly due to a defect in the ______ subunit of integrins.
Neutrophils are attracted by bacterial products, IL-8, C5a, and ______.
Neutrophils are attracted by bacterial products, IL-8, C5a, and ______.
Patients with MPO deficiency are at increased risk for ______ infections.
Patients with MPO deficiency are at increased risk for ______ infections.
Phagocytosis is enhanced by ______ such as IgG and C3b.
Phagocytosis is enhanced by ______ such as IgG and C3b.
O2-independent killing by leukocytes is generally ______ effective than O2-dependent killing.
O2-independent killing by leukocytes is generally ______ effective than O2-dependent killing.
Macrophages derived from ______ in the blood predominate after neutrophils during inflammation.
Macrophages derived from ______ in the blood predominate after neutrophils during inflammation.
The Chediak-Higashi syndrome is characterized by impaired ______ formation.
The Chediak-Higashi syndrome is characterized by impaired ______ formation.
Transmigration of leukocytes occurs across the endothelium of ______ venules.
Transmigration of leukocytes occurs across the endothelium of ______ venules.
Granuloma formation in CGD is primarily associated with catalase-______ organisms.
Granuloma formation in CGD is primarily associated with catalase-______ organisms.
O2 is converted to O2ꜙ by the enzyme ______ during the oxidative burst.
O2 is converted to O2ꜙ by the enzyme ______ during the oxidative burst.
Match the types of inflammation outcomes with their corresponding descriptions:
Match the types of inflammation outcomes with their corresponding descriptions:
Match the stimuli for chronic inflammation with their corresponding descriptions:
Match the stimuli for chronic inflammation with their corresponding descriptions:
Match the types of T cells with their functions:
Match the types of T cells with their functions:
Match the outcomes of macrophage activity with their descriptions:
Match the outcomes of macrophage activity with their descriptions:
Match the phases of T lymphocyte development with their processes:
Match the phases of T lymphocyte development with their processes:
Match the following conditions with their associated characteristics:
Match the following conditions with their associated characteristics:
Match the following components of the oxidative burst with their respective roles:
Match the following components of the oxidative burst with their respective roles:
Match the following test results with their respective conditions:
Match the following test results with their respective conditions:
Match the following organisms with their relevance to CGD:
Match the following organisms with their relevance to CGD:
Match the phase of phagocytosis with its description:
Match the phase of phagocytosis with its description:
Match the following elements of inflammation with their functions:
Match the following elements of inflammation with their functions:
Match the following terms with their definitions:
Match the following terms with their definitions:
Match the following leukocyte characteristics with their effects:
Match the following leukocyte characteristics with their effects:
Match the steps of neutrophil arrival with their descriptions:
Match the steps of neutrophil arrival with their descriptions:
Match the clinical features of Chediak-Higashi syndrome with their descriptions:
Match the clinical features of Chediak-Higashi syndrome with their descriptions:
Match the inflammatory mediators with their roles in fever development:
Match the inflammatory mediators with their roles in fever development:
Match the adhesion molecules with their characteristics:
Match the adhesion molecules with their characteristics:
Match the steps of phagocytosis with their processes:
Match the steps of phagocytosis with their processes:
Match the leukocyte recruitment steps with their processes:
Match the leukocyte recruitment steps with their processes:
Match the conditions or features with their associated mechanisms:
Match the conditions or features with their associated mechanisms:
Match the cytokines with their functions in inflammation:
Match the cytokines with their functions in inflammation:
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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Description
Test your knowledge on the mechanisms of leukocyte function and the implications of chronic granulomatous disease. This quiz covers key concepts such as phagocytosis, inflammation, and the roles of specific immune cells. Dive deep into immunological responses and the effects of various deficiencies.
