Podcast
Questions and Answers
Which component is cleaved by MASP-2 after MBL binds to a pathogen surface?
Which component is cleaved by MASP-2 after MBL binds to a pathogen surface?
What role does C3b play in the complement system?
What role does C3b play in the complement system?
What phenotype is associated with a deficiency in C2 complement components?
What phenotype is associated with a deficiency in C2 complement components?
Which complement deficiency is associated with lupus?
Which complement deficiency is associated with lupus?
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Which outcome is indicated by host cells possessing inhibitors of complement?
Which outcome is indicated by host cells possessing inhibitors of complement?
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What role do tight junctions between epithelial cells play in innate immunity?
What role do tight junctions between epithelial cells play in innate immunity?
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Which component is most directly involved in the phagocytosis of pathogens?
Which component is most directly involved in the phagocytosis of pathogens?
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How does a low pH in the stomach contribute to innate immunity?
How does a low pH in the stomach contribute to innate immunity?
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Which pathway of complement activation would likely be compromised in someone with defective lymphocyte function?
Which pathway of complement activation would likely be compromised in someone with defective lymphocyte function?
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What is the primary function of antimicrobial factors secreted at epithelial surfaces?
What is the primary function of antimicrobial factors secreted at epithelial surfaces?
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What is the primary mediator released by mast cells that causes vasodilation and increases vascular permeability during inflammation?
What is the primary mediator released by mast cells that causes vasodilation and increases vascular permeability during inflammation?
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Which of the following is NOT one of the basic stages of acute inflammation?
Which of the following is NOT one of the basic stages of acute inflammation?
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Which hallmark of inflammation is associated with increased blood flow leading to redness?
Which hallmark of inflammation is associated with increased blood flow leading to redness?
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What is the effect of acute inflammation on lymph flow?
What is the effect of acute inflammation on lymph flow?
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According to historical medical observations, which of the following reflects the pain aspect of inflammation?
According to historical medical observations, which of the following reflects the pain aspect of inflammation?
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What do PAMPs primarily indicate to the immune system?
What do PAMPs primarily indicate to the immune system?
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Which receptors are primarily responsible for recognizing DAMPs?
Which receptors are primarily responsible for recognizing DAMPs?
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What is the function of the inflammasome complex formed by some NLRs?
What is the function of the inflammasome complex formed by some NLRs?
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What type of molecules can be classified as DAMPs?
What type of molecules can be classified as DAMPs?
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Toll-like receptors (TLRs) are primarily involved in recognizing which type of ligands?
Toll-like receptors (TLRs) are primarily involved in recognizing which type of ligands?
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What is one key feature of epithelial surfaces that aids in innate immunity?
What is one key feature of epithelial surfaces that aids in innate immunity?
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What triggers the complement system in the innate immune response?
What triggers the complement system in the innate immune response?
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Which cell types are primarily involved in the innate immune response?
Which cell types are primarily involved in the innate immune response?
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What is a characteristic of the acute inflammatory response?
What is a characteristic of the acute inflammatory response?
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How does the innate immune system recognize 'non-self' entities?
How does the innate immune system recognize 'non-self' entities?
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What distinguishes Pattern Recognition Receptors (PRRs) from other types of receptors in the immune system?
What distinguishes Pattern Recognition Receptors (PRRs) from other types of receptors in the immune system?
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Which of the following is a specific function of NOD-like receptors (NLRs)?
Which of the following is a specific function of NOD-like receptors (NLRs)?
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Damage-Associated Molecular Patterns (DAMPs) primarily indicate what type of cellular state?
Damage-Associated Molecular Patterns (DAMPs) primarily indicate what type of cellular state?
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How many Toll-like Receptors (TLRs) are known to exist in humans?
How many Toll-like Receptors (TLRs) are known to exist in humans?
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Which of the following correctly defines PAMPs?
Which of the following correctly defines PAMPs?
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What is a primary component that some active NLRs can induce?
What is a primary component that some active NLRs can induce?
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Which type of immune cell primarily expresses Pattern Recognition Receptors?
Which type of immune cell primarily expresses Pattern Recognition Receptors?
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Which of the following is NOT a common example of a DAMP?
Which of the following is NOT a common example of a DAMP?
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What key response is primarily triggered by the activation of Toll-like Receptors (TLRs)?
What key response is primarily triggered by the activation of Toll-like Receptors (TLRs)?
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What is one of the roles of extracellular heat-shock proteins in the context of DAMPs?
What is one of the roles of extracellular heat-shock proteins in the context of DAMPs?
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Study Notes
Epithelial Barriers and Complement
- Epithelial surfaces serve as primary physical barriers in innate immunity, lined with cells that create tight junctions to prevent pathogen entry.
- Antimicrobial factors are secreted at epithelial surfaces, contributing to a hostile environment for pathogens.
- The complement system plays a crucial role in the innate immune response, activated through various pathways, including the lectin pathway mediated by Mannose-Binding Lectin (MBL).
- MBL binds pathogen surfaces, initiating a cascade that leads to the cleavage of complement proteins, ultimately tagging pathogens for destruction.
Cells of Innate Immunity & Inflammation
- Key innate immune cells include neutrophils and macrophages, which are essential for phagocytosis and the inflammatory response.
- Neutrophils have a short lifespan but are abundant in blood and respond rapidly to infection.
- Macrophages can reside in healthy tissues, have a longer lifespan, and initiate inflammation when damage occurs.
- Cytokines released by activated macrophages and other cells enhance immune responses and inflammation.
Inflammation Process
- Acute inflammation involves three stages: dilation of small blood vessels, increased permeability of microvasculature, and leukocyte extravasation.
- Symptoms of inflammation are characterized by Celsus’ hallmarks: redness (rubor), swelling (tumor), heat (calor), and pain (dolor).
- Inflammation is a protective response but can also lead to various pathologies if dysregulated.
Recognition of Non-Self and Damage
- The innate immune system recognizes non-self entities through Pattern Recognition Receptors (PRRs), which detect Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs).
- PAMPs include microbial components like bacterial lipids and nucleic acids, whereas DAMPs consist of molecules released upon cell damage.
- TLRs (Toll-Like Receptors) and NLRs (NOD-Like Receptors) are types of PRRs crucial for sensing microbial and damage signals, activating proinflammatory pathways.
Complement System Outcomes and Deficiencies
- The complement system enhances pathogen targeting via opsonization (C3b tagging), promoting phagocytosis and lysis of pathogens.
- Complement deficiencies can lead to serious health issues: C1q deficiency is linked to lupus, C3 deficiency results in severe sepsis, and MAC deficiency predisposes to Neisseria infections.
Inflammation – Acute vs Chronic
- Acute inflammation typically results in edema and the recruitment of cells to combat pathogens, while chronic inflammation may lead to tissue damage and disease.
Learning Objectives Recap
- Distinguish between innate and adaptive immunity based on cell types and response kinetics.
- Explain the contributions of epithelial barriers and the complement system.
- Understand the importance of innate immune cells and the pathways leading to inflammation and tissue healing.
- Elucidate how the innate immune system recognizes threats through specific receptors and mechanisms.
Epithelial Barriers and Complement
- Epithelial surfaces include skin, lungs, gastrointestinal (GI) tract, and reproductive tract, providing crucial defense against pathogens.
- Epithelial tight junctions create a barrier that prevents pathogen entry, while mechanisms like mucociliary escalator and longitudinal flow contribute to mechanical protection.
- Chemical defenses include low pH in the stomach, fatty acids in the skin, and antimicrobial enzymes like lysozyme in tears and saliva.
- Healthy microbiomes in the skin, gut, and respiratory tract also play an essential role in innate immunity.
Cells of Innate Immunity & Inflammation
- Key innate immune cells:
- Macrophages: Tissue-resident, long-lived, derived from blood monocytes, initiate immune responses.
- Neutrophils: Short-lived, abundant, flood sites of inflammation to combat infection.
- Both macrophages and neutrophils utilize phagocytosis, employing receptors and opsonization via complement and antibodies to facilitate particle uptake.
Mechanisms of Phagocyte Action
- Phagocytosis involves the fusion of phagosomes with lysosomes, leading to degradation of pathogens.
- Reactive oxygen species are produced by key enzymes, NADPH oxidase and myeloperoxidase, essential for pathogen killing.
- Deficiencies in these enzymes can result in Chronic Granulomatous Disease, characterized by recurrent infections.
Complement System
- Complement components participate in innate immune response to combat infection, triggered by various pathways.
- Cleavage of C3 into C3a and C3b leads to:
- Phagocytosis of pathogens via opsonization.
- Lysis of pathogens through the formation of the membrane attack complex.
- Activation of inflammatory responses, recruiting additional immune cells.
Recognition of Non-Self and Damage
- Pattern Recognition Receptors (PRRs) are essential for recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).
- PAMPs: Conserved microbial structures, such as bacterial membranes and viral nucleic acids, recognized for signaling an immune response.
- DAMPs: Indicators of cellular damage, including extracellular heat-shock proteins and mitochondrial DNA.
Pattern Recognition Receptors
- Toll-Like Receptors (TLRs): Recognize extracellular microbial ligands; there are 10 TLRs in humans, inducing proinflammatory responses.
- NOD-like Receptors (NLRs): Cytosolic receptors activated by PAMPs and DAMPs, with 22 family members linked to the inflammasome complex and IL-1β release.
- PRRs are expressed by innate immune cells, activating them to initiate immune responses.
Inflammatory Response
- Acute inflammatory responses are characterized by key chemical mediators and cellular activities, aiding in pathogen clearance and healing.
- Key mediators include various interleukins (IL-1, IL-2, IL-3), which contribute to the signaling processes in inflammation.
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Description
Test your knowledge on innate immunity, including epithelial barriers, complement systems, and the cells involved in innate immune responses. This quiz covers essential elements like innate recognition of non-self and damage, vital for understanding the immune system's first line of defense.
