Lecture 02: The innate immune system  [SEQ 2]
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Questions and Answers

What is the primary role of v-ATPases in the phagolysosome formation process?

They acidify the environment by pumping protons

How do reactive oxygen species (ROS) and nitrogen intermediates contribute to microbial killing within a phagolysosome?

They are toxic to the microbe and degrade their components.

Besides microbial killing, what is another important function of the phagolysosome in the context of the immune response?

Antigen presentation

What is the specific role of the TIR domain in the activation of immune genes?

<p>It sends a signal to the cell after TLR binding</p> Signup and view all the answers

Name three types of molecules that are present in lysosomes to promote degradation?

<p>Proteases, lipases, and nucleases</p> Signup and view all the answers

What is the primary function of siderophores in the context of a macrophage's antimicrobial activity?

<p>To remove nutrients from the microbe.</p> Signup and view all the answers

What is the role of NF-κB in the macrophage?

<p>It controls the expression of genes that amplify the inflammatory response.</p> Signup and view all the answers

How does the decrease in pH inside the phagolysosome affect the enclosed microbe?

<p>It creates a hostile environment for it.</p> Signup and view all the answers

What are the two primary cell types responsible for carrying out phagocytosis, and where are they primarily located?

<p>Macrophages, which reside in tissues, and neutrophils, which are recruited from the blood.</p> Signup and view all the answers

Briefly describe the role of opsonization in the process of phagocytosis.

<p>Opsonization involves coating pathogens with opsonins like antibodies, which enhances their recognition and uptake by phagocytes.</p> Signup and view all the answers

What is the primary difference between a PAMP and a PRR in the context of pathogen recognition?

<p>PAMPs are molecular patterns found on pathogens, while PRRs are receptors on immune cells that recognize these patterns.</p> Signup and view all the answers

Describe the function of toll-like receptor 4 (TLR4), including its ligand and location.

<p>TLR4 recognizes lipopolysaccharide (LPS), which is a component of the bacterial cell wall.</p> Signup and view all the answers

Name two types of nucleic acids that can act as Pathogen-Associated Molecular Patterns (PAMPs) and the type of pathogen they are typically associated with.

<p>Double-stranded RNA (dsRNA) and single-stranded RNA (ssRNA) are PAMPs found in viruses.</p> Signup and view all the answers

What is a phagosome and how does it form during phagocytosis?

<p>A phagosome is a large endosome that forms by engulfing a microbe with the phagocyte membrane via the formation of pseudopodia.</p> Signup and view all the answers

List three distinct examples of carbohydrates that can act as PAMPs and state the type of microbe they are associated with.

<p>Mannan (found in fungi and bacteria), glucans (found in fungal cell walls), and peptidoglycan (found in bacterial cell walls)</p> Signup and view all the answers

What initiates phagocytosis after a PAMP binds to a PRR?

<p>Receptor initiated signal transduction and actin rearrangement drives the ingestion of the target cell with the formation of pseudopodia</p> Signup and view all the answers

Flashcards

Phagocytosis

The process by which immune cells engulf and digest pathogens.

Macrophages

Immune cells that reside in tissues and perform phagocytosis.

Neutrophils

Immune cells recruited from the blood to fight infections.

PAMPs

Pathogen Associated Molecular Patterns recognized by immune cells.

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PRRs

Pattern Recognition Receptors on immune cells that detect PAMPs.

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Opsonization

The process where pathogens are coated to enhance phagocytosis.

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Toll-like receptors (TLRs)

Type of PRRs that detect specific PAMPs like bacteria and viruses.

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Phagosome

A compartment formed when a pathogen is engulfed during phagocytosis.

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Fusion with Early Endosomes

Process where phagosomes interact with early endosomes to trigger maturation and recruit signaling molecules.

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Fusion with Late Endosomes

Further fusion with late endosomes which begins acidification and creates a hostile environment for microbes.

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Fusion with Lysosomes

Combining phagosomes with lysosomes to form phagolysosomes for microbial degradation.

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Microbial Killing Mechanisms

Inside phagolysosomes, acidic conditions and enzymes kill and digest microbes into harmless components.

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Reactive Oxygen Species (ROS)

Toxic molecules produced in phagolysosomes for killing microbes, including superoxide and hypochlorite.

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NF-kB

A central transcription factor activated in immune responses that regulates genes involved in inflammation.

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Cytokines

Signaling proteins produced during immune responses that recruit and activate immune cells.

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Inflammatory Proteins

Mediators controlled by NF-kB that amplify inflammatory responses during immune reactions.

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Study Notes

Phagocytosis Overview

  • Phagocytosis is a process where immune cells engulf and destroy pathogens.
  • Key cells involved are macrophages (resident tissues) and neutrophils (recruited from blood).
  • The process involves several steps: chemotaxis, attachment, ingestion, lysosome fusion, microbial killing & digestion, and waste release.

Steps in Phagocytosis

  • Chemotaxis: Attraction of phagocytes to the site of infection.
  • Attachment: Phagocyte binds to the pathogen via surface receptors.
  • Ingestion: The pathogen is engulfed by the phagocyte, forming a phagosome.
  • Phagosome Formation: The phagosome is the vesicle containing the engulfed pathogen.
  • Lysosome Fusion: The phagosome fuses with lysosomes, creating a phagolysosome.
  • Microbial Killing and Digestion: Lysosomal enzymes (e.g., proteases, lipases) and ROS/RNOS break down the pathogen; the acidic environment of the phagolysosome also contributes.
  • Debris Release: Waste products are expelled, or the pathogen components can be processed for antigen presentation.

Recognizing Microbes

  • PAMPs (Pathogen-Associated Molecular Patterns): Unique molecular structures on pathogens.

  • PRRs (Pattern Recognition Receptors): Found on immune cells, they recognize PAMPs.

  • TLR (Toll-like Receptors): A class of PRRs, with diverse ligand recognition capabilities. Key TLRs include:

    • TLR2: Recognizes peptidoglycans (bacterial cell wall component).
    • TLR4: Recognizes lipopolysaccharide (LPS) (bacterial cell wall component).
    • TLR5: Recognizes flagellin (bacterial appendage).
    • TLR7: Recognizes ssRNA (viral).
    • TLR9: Recognizes dsRNA (viral/bacterial).
    • TLR10: Recognizes flagellin (bacterial appendage).

Opsonization

  • Opsonization: Coating of pathogens with opsonins (like antibodies or complement proteins) to enhance phagocytosis.
  • Steps:
    • Antibody tagging: Antibodies mark a pathogen.
    • Recognition: Phagocytes recognize the antibodies.
    • Engulfing: Phagocyte binds and ingests the pathogen.
    • Killing: The pathogen is destroyed within the phagocyte.

Phagosome Maturation

  • Formation: The internalisation of the pathogen into a phagosome.
  • Early Endosome Interaction: The phagosome fuses with early endosomes, which provide specific proteins.
  • Late Endosome Fusion: The phagosome fuses with late endosomes where the lysosomal enzymes are present along with the proton pumps, that decrease pH.
  • Lysosome Fusion: The phagosome fuses with lysosomes to form a phagolysosome.

Microbial Killing & Debris Clearance

  • Phagocytosis vs. Microbial Clearance and Digestion: Interior environment with acidic PH reduces pH to 3.5-4
  • ROS (Reactive Oxygen Species): Toxic molecules generated to kill the pathogen.
  • AMP (Antimicrobial Peptides): e.g., defensins, cationic peptides form ion channels in the membrane
  • Enzymes (Lysosomal): Break down pathogen structures (peptidoglycans, polysaccharides).
  • Nutrient Deprivation: Removal of nutrients required by pathogens.

Signaling and Immune Response

  • Cytokines: Signal molecules to recruit and activate other immune cells.
  • Inflammatory proteins: Amplify the inflammatory response.
  • NF-κB: Key transcription factor activated by TLR signalling.
  • Inflammation and immune gene expression: The process is regulated and controls expressions of cytokines, inflammatory mediators etc
  • Phagolysosomal protein upregulation: Proteins are altered to enhance the killing and degradation process inside the phagolysosome

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Description

This quiz explores the essential process of phagocytosis, where immune cells like macrophages and neutrophils engulf and destroy pathogens. Students will learn the key steps involved, including chemotaxis, attachment, ingestion, and more. Gain a deeper understanding of how immune cells protect the body from infections.

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