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Questions and Answers
What mediates the firm attachment of leukocytes to the endothelium during recruitment?
What mediates the firm attachment of leukocytes to the endothelium during recruitment?
Which of the following cytokines is known to increase the avidity of integrins for their ligands?
Which of the following cytokines is known to increase the avidity of integrins for their ligands?
During phagocytosis, what is the first step that occurs?
During phagocytosis, what is the first step that occurs?
Which receptor specifically recognizes microbial sugars rather than host cell components?
Which receptor specifically recognizes microbial sugars rather than host cell components?
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Which cells primarily predominate the early inflammatory infiltrate during immune response?
Which cells primarily predominate the early inflammatory infiltrate during immune response?
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What process allows selected circulating proteins to enter the site of infection or tissue damage?
What process allows selected circulating proteins to enter the site of infection or tissue damage?
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Which cells are primarily responsible for the ingestion and destruction of microbes in tissues?
Which cells are primarily responsible for the ingestion and destruction of microbes in tissues?
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What characterizes the endothelium lining blood vessels during an inflammatory response?
What characterizes the endothelium lining blood vessels during an inflammatory response?
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Which of the following is a potential harmful consequence of inflammation?
Which of the following is a potential harmful consequence of inflammation?
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What typically happens to harmful consequences of inflammation over time?
What typically happens to harmful consequences of inflammation over time?
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What role do cytokines and growth factors play in the inflammatory response?
What role do cytokines and growth factors play in the inflammatory response?
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Which substances contribute to the extracellular matrix during an inflammatory reaction?
Which substances contribute to the extracellular matrix during an inflammatory reaction?
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What does the presence of streaks indicating lymphangitis signify?
What does the presence of streaks indicating lymphangitis signify?
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Which mediator is primarily responsible for inducing vasodilation in acute inflammation?
Which mediator is primarily responsible for inducing vasodilation in acute inflammation?
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What is one consequence of increased vascular permeability during inflammation?
What is one consequence of increased vascular permeability during inflammation?
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What condition may accompany lymphangitis, indicating further inflammation?
What condition may accompany lymphangitis, indicating further inflammation?
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What role do leukocytes play in the context of increased vascular permeability?
What role do leukocytes play in the context of increased vascular permeability?
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Which of the following is not a function of lymphatic vessels during inflammation?
Which of the following is not a function of lymphatic vessels during inflammation?
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What results from the leak of plasma proteins due to increased vascular permeability?
What results from the leak of plasma proteins due to increased vascular permeability?
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What is a major factor contributing to increased vascular permeability in acute inflammation?
What is a major factor contributing to increased vascular permeability in acute inflammation?
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Which chemical mediator is specifically mentioned as causing gaps between endothelial cells?
Which chemical mediator is specifically mentioned as causing gaps between endothelial cells?
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What role do adhesion molecules play in leukocyte migration?
What role do adhesion molecules play in leukocyte migration?
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Which integrin state is associated with stable adhesion of leukocytes?
Which integrin state is associated with stable adhesion of leukocytes?
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What signals lead to the activation of integrins in leukocytes?
What signals lead to the activation of integrins in leukocytes?
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Which molecules are necessary for the rolling phase of leukocyte migration?
Which molecules are necessary for the rolling phase of leukocyte migration?
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Which component of the extracellular matrix is mentioned in relation to macrophages and microbes?
Which component of the extracellular matrix is mentioned in relation to macrophages and microbes?
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What is the primary function of PECAM-1 (CD31) in leukocyte migration?
What is the primary function of PECAM-1 (CD31) in leukocyte migration?
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Leukocytes sense signals during migration primarily through which types of molecules?
Leukocytes sense signals during migration primarily through which types of molecules?
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What happens to integrins during the activation phase of leukocyte migration?
What happens to integrins during the activation phase of leukocyte migration?
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What is the primary outcome of the leukocyte migration process described?
What is the primary outcome of the leukocyte migration process described?
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The initial rolling of leukocytes is primarily characterized by what type of interaction?
The initial rolling of leukocytes is primarily characterized by what type of interaction?
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What is the primary role of actin polymerization in leukocyte migration?
What is the primary role of actin polymerization in leukocyte migration?
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In acute inflammation, which leukocyte type predominates in the initial response within the first 6 to 24 hours?
In acute inflammation, which leukocyte type predominates in the initial response within the first 6 to 24 hours?
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What is a consequence of using antagonists of leukocyte integrins in treatment?
What is a consequence of using antagonists of leukocyte integrins in treatment?
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Which cell type is often the first to arrive in response to viral infections?
Which cell type is often the first to arrive in response to viral infections?
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What triggers the initial attachment of neutrophils to endothelial cells during inflammation?
What triggers the initial attachment of neutrophils to endothelial cells during inflammation?
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In allergic reactions, which type of leukocyte is primarily involved?
In allergic reactions, which type of leukocyte is primarily involved?
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How does the infiltration of leukocytes change during the inflammatory response?
How does the infiltration of leukocytes change during the inflammatory response?
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What is the main effect of chemoattractants in the inflammatory response?
What is the main effect of chemoattractants in the inflammatory response?
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Which of the following statements about the recruitment of leukocytes is correct?
Which of the following statements about the recruitment of leukocytes is correct?
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In what way does the presence of activated lymphocytes, macrophages, and plasma cells reflect the immune response?
In what way does the presence of activated lymphocytes, macrophages, and plasma cells reflect the immune response?
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Study Notes
Overview of Inflammation: Definitions and General Features
- Inflammation is a vascularized tissue response that delivers leukocytes and host defense molecules to sites of infection or cell damage to eliminate the threat.
- Inflammation is a protective response essential for survival.
- Inflammation involves phagocytic leukocytes, antibodies, and complement proteins.
- Inflammation normally resides in the blood, capable of rapid recruitment to any body site.
- Inflammation includes processes that deliver cells and proteins into tissues, activating recruited cells/proteins to eliminate harmful substances.
- The suffix "-itis" signifies inflammation in a specific organ (e.g., appendicitis, conjunctivitis).
- The inflammatory reaction follows a series of steps.
Historical Highlights
- Clinical observations of inflammation date back to 3000 BCE (Egyptian papyrus).
- Celsus (1st century AD) identified the four cardinal signs of acute inflammation: redness, swelling, heat, and pain.
- John Hunter (1793) recognized inflammation as a body response, not a disease.
- Elie Metchnikoff (1880s) discovered phagocytosis.
- Thomas Lewis emphasized the role of chemical mediators of inflammation.
Causes of Inflammation
- Infections (bacterial, viral, fungal, parasitic) and microbial toxins are the most common causes.
- Tissue necrosis from ischemia, trauma, physical/chemical injury triggers inflammation.
- Foreign bodies/endogenous substances (urate crystals, etc.) can trigger inflammation.
- Immune reactions (hypersensitivity) can cause inflammation and tissue damage.
Recognition of Microbes and Damaged Cells
- Sentinel cells (e.g., macrophages) recognize microbial components and damaged cell products triggering an inflammatory response.
- TLRs and other cellular receptors sense foreign invaders.
- Damage-sensing sensors (e.g., NLRs) recognize molecules from damaged cells initiating inflammasome activation and IL-1 production, resulting in inflammation.
Acute Inflammation
- Characterized by:
- Dilation of blood vessels increasing blood flow
- Increased microvasculature permeability allowing plasma proteins and leukocytes to leave the blood
- Leukocyte emigration, accumulation at the site of injury, and their activation to eliminate the offending agent
- The vascular reactions involve changes in blood flow and permeability maximizing the movement of plasma proteins/leukocytes to the site of injury.
- Exudate (high protein, cellular debris) differs from a transudate (low protein).
Increased Vascular Permeability
- Histamine, bradykinin, leukotrienes constrict endothelial cells creating gaps in venules, allowing fluid and proteins to escape.
- Endothelial injury leads to endothelial cell necrosis and detachment.
Leukocyte Recruitment to Sites of Inflammation
- Margination. Red blood cells move to center of blood vessels causing white blood cells (leukocytes) to move to the outer edges of blood vessel.
- Rolling. Leukocytes loosely attach and roll along endothelial walls via selectin molecules.
- Stable adhesion. Rolling is followed by firm adhesion via integrin molecules.
- Migration through endothelium. Leukocytes migrate through the endothelium via gaps between endothelial cells.
Chemotaxis of Leukocytes
- Chemotaxis is the movement of cells along a chemical gradient.
- Exogenous or endogenous substances act as chemoattractants (microbial products, cytokines).
- Macrophages, neutrophils predominate in the first 6-24 hours, replaced by monocytes later.
Phagocytosis and Clearance of Offending Agents
- Phagocytosis. Recognition and attachment of particle to be ingested leading to engulfment and the formation of a phagocytic vacuole and subsequent killing and degradation.
- Phagocytes. Neutrophils and macrophages.
- Phagocytic receptors (e.g., mannose), receptors for opsonins (IgG antibodies, C3b).
- Intracellular destruction. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed inside phagocytic vacuoles, as well as lysosomal enzymes.
Mediators of Inflammation
- Many substances (vasoactive amines, lipid mediators, cytokines, complement system products) initiate/regulate inflammatory reactions.
- Sources of mediators include macrophages, dendritic cells, mast cells.
- These mediators have overlapping actions.
- Mediators are short-lived, thus regulation mechanisms exist.
Systemic Effects of Inflammation
- Fever.
- Acute-phase proteins.
- Leukocytosis.
- Septic shock (severe infection).
Morphological Patterns of Acute Inflammation
- Serous inflammation. Leaking of cell-poor fluid into spaces caused by injury or body cavities.
- Fibrinous inflammation. Increased vascular leakage causing leakage of larger molecules like fibrinogen leading to fibrinous exudate.
- Purulent (suppurative) inflammation & Abscess. Production of pus (neutrophils, liquefied debris).
Chronic Inflammation
- Prolonged, weeks-months.
- Causes: persistent infection, hypersensitivity, prolonged exposure to toxic agents.
- Characterized by mononuclear cell infiltration, tissue destruction, attempts at healing (angiogenesis, fibrosis).
- Granulomatous inflammation. (Formation of granulomas, e.g., in tuberculosis, Crohn's disease).
Cells and Mediators of Chronic Inflammation
- Macrophages: Dominant cells that secrete cytokines/growth factors.
- Lymphocytes: Amplify inflammatory reactions by activating more macrophages via cytokine signaling.
- Other cells: eosinophils, mast cells.
Tissue Repair
- Regeneration of cells/tissues to normal states.
- Connective tissue deposition (scar formation).
- Steps in scar formation: Inflammation, cell proliferation (angiogenesis, fibroblast proliferation), connective tissue deposition (Collagen).
Healing of Skin Wounds
- Healing by primary intention (clean incision): epithelial regeneration (migration, mitosis), granulation tissue filling.
- Healing by secondary intention (large wound): more inflammation, exudate and debris, more granulation tissue, contraction.
Factors that Influence Tissue Repair
- Infection.
- Diabetes.
- Nutrition.
- Glucocorticoids.
- Poor perfusion.
- Foreign bodies.
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Description
Test your knowledge on the processes involved in leukocyte recruitment and the role of cytokines in immune responses. This quiz covers topics such as phagocytosis, receptor recognition, and the early cellular response during inflammation. Perfect for students studying immunology and related fields.