Podcast
Questions and Answers
Which type of pathogen-associated molecular pattern (PAMP) is recognized by TLR4?
Which type of pathogen-associated molecular pattern (PAMP) is recognized by TLR4?
What is the primary role of opsonization in the immune response?
What is the primary role of opsonization in the immune response?
Which Toll-like receptor (TLR) specifically recognizes flagellin?
Which Toll-like receptor (TLR) specifically recognizes flagellin?
Which statement about phagocytosis is incorrect?
Which statement about phagocytosis is incorrect?
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What is the role of Pattern Recognition Receptors (PRRs) in the innate immune system?
What is the role of Pattern Recognition Receptors (PRRs) in the innate immune system?
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Which component primarily differentiates gram-positive bacteria from gram-negative bacteria?
Which component primarily differentiates gram-positive bacteria from gram-negative bacteria?
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Which of the following is NOT a step in the phagocytosis process?
Which of the following is NOT a step in the phagocytosis process?
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What happens during the tagging step of opsonization?
What happens during the tagging step of opsonization?
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What role do hydrolytic enzymes play in the phagolysosome?
What role do hydrolytic enzymes play in the phagolysosome?
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How does pH reduction in the phagolysosome contribute to microbial killing?
How does pH reduction in the phagolysosome contribute to microbial killing?
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What is the function of reactive oxygen species (ROS) in the immune response?
What is the function of reactive oxygen species (ROS) in the immune response?
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What triggers the expression of immune genes upon receptor binding?
What triggers the expression of immune genes upon receptor binding?
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What role do AMPs (antimicrobial peptides) play in the phagosome?
What role do AMPs (antimicrobial peptides) play in the phagosome?
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What happens to debris resulting from the degradation of microbes?
What happens to debris resulting from the degradation of microbes?
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Which of the following correctly describes NF-kB's role in the immune response?
Which of the following correctly describes NF-kB's role in the immune response?
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How do nutrient transporters aid macrophages in fighting infections?
How do nutrient transporters aid macrophages in fighting infections?
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Study Notes
Innate Immune System: Phagocytosis
- Phagocytes: Macrophages (tissue resident) and neutrophils (blood-derived) are key phagocytic cells.
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Phagocytosis Steps:
- Chemotaxis: Attraction to the target.
- Attachment: Receptors bind to pathogen-associated molecular patterns (PAMPs).
- Ingestion: Formation of a phagosome around the pathogen.
- Fusion: Phagosome fuses with lysosomes.
- Killing & Digestion: Enzymes, reactive oxygen species (ROS) and reactive nitrogen species (RNS), and a reduced pH degrade the pathogen.
- Release: Waste products are released and some digested material is processed for antigen presentation.
- Recognizing Microbes: PAMPs (on microbes) are recognized by PRRs (on phagocytes), most notably, TLRs.
- Pattern Recognition Receptors (PRRs): Macrophages express TLRs for specific PAMP detection.
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Toll-like Receptors (TLRs): A diverse set of TLRs exist, each recognizing specific PAMPs. Example TLRs:
- TLR2: Recognizes Peptidoglycan (bacterial cell wall component).
- TLR4: Recognizes Lipopolysaccharide (LPS) (bacterial cell wall component).
- TLR5: Recognizes Flagellin (bacterial flagella).
- TLR7: Recognizes ssRNA (from viruses like influenza and HIV-2).
- TLR9: Recognizes dsDNA (from bacteria and herpes simplex virus).
- TLR10: Recognizes Flagellin (bacterial flagella).
PAMPs (Pathogen-Associated Molecular Patterns)
- Characteristics: PAMPs are conserved molecular patterns on microbes. They are not easily mutated, therefore providing consistent markers for immune response.
- Types: Nucleic acids (viral RNA), proteins (flagellin, pilin), lipids (LPS, lipotechoic acid), carbohydrates (mannan, glucans, peptidoglycan).
Opsonization
- Definition: The coating of pathogens with opsonins (e.g., antibodies, complement proteins) to enhance phagocytosis.
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Process:
- Tagging: Antibodies mark the pathogen for destruction.
- Recognition: Macrophages recognize the antibody's Fc region.
- Engulfing: The macrophage binds and engulfs the pathogen.
- Killing: The pathogen is destroyed inside the macrophage.
Phagosome Maturation
- Phagosome Formation: The phagocyte engulfs the microbe within a phagosome, a large endosome.
- Early Endosome Fusion: The phagosome interacts with early endosomes, which deliver maturation proteins.
- Late Endosome Fusion: Further fusion with late endosomes leads to acidification (pH decrease).
- Lysosome Fusion: The phagosome fuses with lysosomes to create a phagolysosome. Lysosomes contain lytic enzymes and generate ROS for microbial kill.
Microbial Killing and Digestion
- Phagolysosome Contents: The acidic environment, lysosomal enzymes, and ROS destroy and break down microbes.
Debris Clearance
- Disposal: Digested or remaining waste is released or processed for antigen presentation to adaptive immune cells.
Macrophage Killing Mechanisms
- Acidification: Lowering of pH via H+ ATPase pumps.
- Reactive Oxygen Species (ROS): Hypochlorite (bleach), nitric oxide.
- Antimicrobial Peptides (AMPs): Defensins, cationic peptides for membrane disruption.
- Enzymes: Lysozyme degrades peptidoglycan.
- Nutrient Removal: Siderophores and nutrient transporters.
Signaling and Immune Gene Expression
- TLR Signaling: TLR engagement activates downstream signaling, typically involving the transcription factor NF-κB.
- NF-κB Activation: Leads to increased expression of immune response genes, promoting AMP production, enhancing phagocyte killing, inducing cytokine production, and stimulating inflammatory mediators.
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Description
Explore the intricacies of phagocytosis within the innate immune system. This quiz covers the key steps involved, the role of phagocytes like macrophages and neutrophils, and the importance of pattern recognition receptors in identifying pathogens. Test your knowledge on how our body defends against infections!
