Phagocytosis Overview and Steps
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Questions and Answers

What is the primary role of proteins delivered to early endosomes during phagosome maturation?

They initiate the maturation process and recruit signaling molecules and enzymes.

How does the activity of v-ATPases contribute to the hostile environment within late endosomes?

They pump protons into the endosome, acidifying the environment, causing the pH to decrease.

Besides hydrolytic enzymes, what other toxic substances are delivered by lysosomes into the phagolysosome?

Reactive oxygen species (ROS) and nitrogen intermediates.

How is the debris from digested microbes handled after phagolysosome maturation?

<p>It is either released as waste or processed for antigen presentation.</p> Signup and view all the answers

What is the typical pH range achieved by acidification within the phagolysosome?

<p>The pH is reduced to between 3.5 and 4.</p> Signup and view all the answers

What is the primary role of opsonization in the immune response?

<p>Opsonization enhances the recognition and uptake of pathogens by phagocytes.</p> Signup and view all the answers

Name two specific reactive oxygen species (ROS) that macrophages use to kill microbes in the phagolysosome.

<p>Hypochlorite (OCL-) and superoxide.</p> Signup and view all the answers

What is the role of the TIR domain in macrophage activation?

<p>It signals the cell to express immune genes.</p> Signup and view all the answers

Describe the location and ligand of Toll-like receptor 4 (TLR4).

<p>TLR4 is located on the cell wall of bacteria and it recognizes lipopolysaccharide (LPS).</p> Signup and view all the answers

Name two types of cells that are capable of carrying out phagocytosis.

<p>Macrophages and neutrophils.</p> Signup and view all the answers

What is the main shared transcription factor downstream of TLR signaling that upregulates inflammatory response?

<p>NF-κB.</p> Signup and view all the answers

What is a Pathogen-Associated Molecular Pattern (PAMP) and provide two examples?

<p>PAMPS are microbial molecules not easily mutated and that are recognised by immune cell receptors. Examples include lipopolysaccharide (LPS) and flagellin.</p> Signup and view all the answers

Explain the process of phagosome formation during phagocytosis.

<p>The cell membrane uses pseudopodia to surround and engulf the target microbe, sequestering it into an endosome known as a phagosome.</p> Signup and view all the answers

How do Pattern Recognition Receptors (PRRs) interact with Pathogen-Associated Molecular Patterns (PAMPs)?

<p>PRRs located on immune cells bind to PAMPs found on the surface of microbes, initiating an immune response.</p> Signup and view all the answers

Name two ligands that TLRs recognize in viruses?

<p>ssRNA and dsDNA</p> Signup and view all the answers

List two types of carbohydrates considered as PAMPs.

<p>Mannan and glucans.</p> Signup and view all the answers

Flashcards

Phagocytosis

The process by which cells engulf and digest pathogens or particles.

PRRs

Pattern Recognition Receptors that recognize PAMPs on pathogens.

PAMPs

Pathogen Associated Molecular Patterns recognized by PRRs.

TLR

Toll-like receptors that detect specific PAMPs.

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Opsonization

The process of marking pathogens for destruction by coating them with opsonins.

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Chemotaxis

The movement of cells towards chemical signals, usually from infection sites.

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Macrophages

Large immune cells that engulf and digest pathogens; reside in tissues.

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Neutrophils

Type of white blood cell recruited from the blood to fight infections.

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Early Endosomes

Membrane-bound compartments that interact with phagosomes to initiate maturation.

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Proton Pumps (v-ATPases)

Enzymes that acidify the environment of endosomes and lysosomes.

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Phagolysosome

A fused structure of phagosome and lysosome containing hydrolytic enzymes.

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Reactive Oxygen Species (ROS)

Toxic molecules produced in phagolysosomes that help kill microbes.

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Antigen Presentation

The process of processing microbial debris for immune response activation.

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NF-kB

A key transcription factor that regulates immune gene expression.

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Cytokines

Signaling proteins that recruit and activate various immune cells.

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Inflammatory Proteins

Mediators controlled by NF-kB that enhance the inflammatory response.

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Study Notes

Phagocytosis Overview

  • Phagocytosis is a crucial process of the innate immune system, where immune cells engulf and destroy pathogens.
  • Key phagocytic cells include macrophages (resident in tissues) and neutrophils (recruited from blood).
  • The process involves several steps: chemotaxis, attachment, ingestion, lysosome fusion, microbial killing, and waste release.

Steps of Phagocytosis

  • Chemotaxis: Immune cells are attracted to the site of infection by chemical signals.
  • Attachment: Receptors on the immune cell bind to pathogen-associated molecular patterns (PAMPs) on the microbe's surface.
  • Ingestion & Phagosome Formation: The cell membrane engulfs the microbe, forming a phagosome (a vesicle).
  • Lysosome Fusion: Lysosomes, containing digestive enzymes and antimicrobial substances, fuse with the phagosome, forming a phagolysosome.
  • Microbial Killing & Digestion: The acidic environment, enzymes, and reactive oxygen species (ROS) within the phagolysosome kill and break down the pathogen.
  • Waste Release: The waste products are released from the cell.

Recognizing Microbes

  • PAMPs (Pathogen-Associated Molecular Patterns): Unique molecular structures on pathogens that are easily recognized by the immune system.
  • PRRs (Pattern Recognition Receptors): Receptors on immune cells that recognize PAMPs. Macrophages have various PRRs.
    • Toll-like receptors (TLRs): A diverse family of PRRs crucial for recognizing different microbial components. Thirteen different types are known.
      • Specific examples of TLRs & their ligands:
        • TLR2: Peptidoglycan (bacterial cell wall component)
        • TLR4: Lipopolysaccharide (LPS) (bacterial cell wall component)
        • TLR5: Flagellin (bacterial appendage)
        • TLR7: ssRNA (viruses like influenza and HIV-2)
        • TLR9: dsDNA (bacteria and herpes simplex virus)
        • TLR10: Flagellin (bacterial appendage)

Opsonization

  • Opsonization enhances phagocytosis.
  • Pathogens or particles are coated with opsonins (like antibodies or complement proteins).
  • This coating enhances their recognition and uptake by phagocytes, leading to more efficient elimination of pathogens.
  • The steps in opsonization:
    • Tagging: Antibody coats the pathogen.
    • Recognition: Macrophages recognize the antibody.
    • Engulfing: Macrophage binds and engulfs the pathogen.
    • Killing: The pathogen is destroyed inside the macrophage.

Phagosome Formation and Maturation

  • Phagosome: A vesicle formed from engulfing the pathogen.
  • Phagosome maturation involves interaction with other intracellular organelles (endosomes), leading to crucial changes in pH and environment that help in microbial killing.
    • Fusion with early endosomes: Delivers essential proteins initiating maturation.
    • Fusion with late endosomes: Acidification begins due to proton pumps (v-ATPases).
    • Fusion with lysosomes: Phagolysosome formation. This provides hydrolytic enzymes and ROS to kill the bacteria.

Microbial Killing & Debris Clearance

  • Killing Mechanisms: Acidification, ROS (like hypochlorite, nitric oxide, superoxide, peroxynitrite), antimicrobial peptides (AMPs like defensins), and lysosomal enzymes break down the microbe.
  • Debris Clearance: The broken-down remains may be released as waste or used for antigen presentation, connecting innate and adaptive immunity.

Cell Signaling and Immune Gene Expression

  • TLR binding triggers cell signaling pathways.
  • NF-κB: A crucial transcription factor activated in response to microbial recognition, controlling the expression of various immune genes.
  • Cytokines: Immune signaling proteins induced by microbial recognition and participate in activating other immune cells.
  • Inflammatory Proteins: Mediators whose production is regulated by NF-κB that amplify the inflammatory response.
  • Other molecules Phagosomal proteins and inflammatory proteins also influence the efficiency of microbial killing.

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Description

This quiz explores the process of phagocytosis, a vital function of the innate immune system. You will learn about the key cells involved, including macrophages and neutrophils, as well as the detailed steps of this immune response. Test your understanding of chemotaxis, ingestion, and microbial killing.

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