Lecture 02: The innate immune system [MCQ 2]

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Questions and Answers

Which of the following is NOT a direct function of opsonisation?

Directly killing the pathogen (correct)

Enhancing recognition of pathogens by phagocytes

Facilitating the engulfment of pathogens

Tagging pathogens for destruction

Which Toll-like receptor (TLR) is most directly involved in the recognition of lipopolysaccharide (LPS)?

TLR2

TLR4 (correct)

TLR5

TLR7

What is the primary ligand recognized by TLR5?

Single-stranded RNA

Flagellin (correct)

Peptidoglycan

Double-stranded DNA

Which of the following microbial components would NOT be classified as a PAMP?

Fc region of an antibody (B) Signup and view all the answers

During phagocytosis, what structures are formed when the cell membrane extends around the target microbe?

Pseudopodia (C) Signup and view all the answers

Which of the following best describes the function of Pattern Recognition Receptors (PRRs)?

To identify and bind to Pathogen Associated Molecular Patterns (PAMPs) (B) Signup and view all the answers

Where would you expect to find glucans?

Fungal cell wall (C) Signup and view all the answers

Which of the following Toll-like receptors (TLRs) is known to recognize single-stranded RNA?

TLR7 (B) Signup and view all the answers

What is the correct sequence of the events in phagocytosis after attachment has occurred?

Ingestion -> Lysosome fusion -> Microbial killing -> Waste release (B) Signup and view all the answers

Which of the following describes the role of the phagosome?

To engulf the microbe within a membrane bound compartment (A) Signup and view all the answers

What is the primary role of hydrolytic enzymes in the phagolysosome?

They degrade microbial components into small, non-harmful units. (C) Signup and view all the answers

What effect does the fusion of phagosomes with lysosomes have on the pH within the phagolysosome?

It lowers the pH, creating a hostile environment for the microbes. (D) Signup and view all the answers

How do reactive oxygen species (ROS) contribute to microbial killing?

By creating oxidative stress that is toxic to microbes. (C) Signup and view all the answers

What is the function of the TLRs (Toll-like receptors) in the immune response?

They signal the cell to express immune genes upon pathogen binding. (B) Signup and view all the answers

Which of the following accurately describes the role of NF-κB in the immune response?

It serves as a transcription factor that regulates immune gene expression. (C) Signup and view all the answers

What is an effect of the cationic peptides (AMPs) produced during the immune response?

They create ion pores in the microbial membrane to induce cell lysis. (A) Signup and view all the answers

What role do siderophores play in the immune response?

They transport and sequester iron, limiting nutrient availability to pathogens. (D) Signup and view all the answers

Which substances are involved in controlling the inflammatory response?

Cytokines and inflammatory proteins. (B) Signup and view all the answers

What results from the removal of debris after phagocytosis?

It can be processed for antigen presentation. (D) Signup and view all the answers

Which of the following statements about the acidification process in phagocytosis is true?

It creates a pH environment optimal for lysosomal enzyme activity. (D) Signup and view all the answers

Study Notes

Innate Immune System: Phagocytosis

Phagocytes: Macrophages (resident in tissues) and neutrophils (recruited from blood) are crucial for phagocytosis.
Steps in Phagocytosis:
- Chemotaxis: Phagocytes are attracted to the site of infection.
- Attachment: Receptors on the phagocyte bind to pathogen-associated molecular patterns (PAMPs) on the microbe's surface.
- Ingestion and Phagosome Formation: The phagocyte engulfs the microbe, forming a phagosome.
- Lysosome Fusion: The phagosome fuses with lysosomes, forming a phagolysosome.
- Microbial Killing and Digestion: Enzymes, ROS, and the acidic environment in the phagolysosome kill and break down the microbe.
- Release of Waste: Undigested material is released.

Recognizing Microbes

PAMPs and PRRs: Pathogen-associated molecular patterns (PAMPs) on microbes are recognized by pattern recognition receptors (PRRs) on phagocytes.
Macrophage PRRs (e.g., Toll-like receptors): Macrophages possess various TLRs, each recognizing specific microbial components.
- TLR2: Recognizes peptidoglycan (bacterial cell wall).
- TLR4: Recognizes lipopolysaccharide (LPS; bacterial cell wall).
- TLR5: Recognizes flagellin (bacterial flagella).
- TLR7: Recognizes ssRNA (viruses like influenza and HIV-2).
- TLR9: Recognizes dsDNA (bacteria and herpes viruses).
- TLR10: Recognizes flagellin (bacterial flagella). There are 13 different types of TLRs in total.
Types of PAMPS: - Nucleic acids: Double-stranded RNA (dsRNA) and single-stranded RNA (ssRNA) found in viruses. - Proteins: Flagellin (bacterial flagella), pilin (bacterial pili). - Lipids: Lipopolysaccharide (LPS) in Gram-negative cell walls, and lipoteichoic acid in Gram-positive cell walls. - Carbohydrates: Mannan (fungi and bacteria), glucans (fungi), peptidoglycan (bacteria).

Opsonization:

Opsonization is a process where pathogens are coated with opsonins (like antibodies or complement proteins).
This enhances phagocyte binding and phagocytosis.
Steps:
- Tagging: Antibodies coat the pathogen.
- Recognition: Macrophages recognize the antibody's Fc region using their Fc receptors.
- Engulfing: The macrophage binds to the antibody and engulfs the pathogen.
- Killing: The pathogen is destroyed within the phagolysosome.

Phagosome Maturation

Phagosome Formation: The microbe is engulfed.
Phagosome-Endosome Interactions: The phagosome interacts with early endosomes, which contribute proteins to initiate maturation.
Phagosome-Late Endosome Interactions:The maturing phagosome fuses with late endosomes. This step creates an increasingly acidic environment.
Phagosome-Lysosome Fusion: The phagosome fuses with a lysosome, creating a phagolysosome.

Microbial Killing and Digestion

Phagolysosome environment: The phagolysosome contains hydrolytic enzymes (proteases, lipases), ROS, and an acidic environment (pH 3.5-4) to kill and digest the pathogen.

Debris Clearance

Waste Disposal: Indigested material is either released as waste or processed to present antigens, triggering adaptive immunity.

Mechanisms of Microbial Killing

Acidification: Decreasing the pH (3.5-4) via H+ ATPase pumps.
Reactive Oxygen Species (ROS): e.g., hypochlorite(OCL-), nitric oxide, superoxide, peroxynitrite.
Antimicrobial Peptides (AMPS): Defensins create ion pores in the microbial membrane.
Enzymes: Lysozymes degrade peptidoglycan in Gram-positive bacteria. Ribonucleases (RNases), DNases, and proteases degrade other components.
Nutrient Depletion: Siderophores and nutritional transport systems deprive microbes of essential nutrients.

Cellular Signaling and Immune Gene Expression

TLR Signal Transduction: Binding of PAMPs to TLRs initiates signaling pathways, leading to the expression of immune genes.
Transcription Factors: The key transcription factor NF-κB is activated.
Cytokines: Production of cytokines is induced, recruiting and activating other immune cells.
AMPS and Inflammatory Mediators: Mediators that amplify the inflammatory response are up-regulated.
Phagosomal Proteins: Proteins involved in phagosome maturation and microbial degradation are enhanced.

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Description

This quiz explores the key components and processes of the innate immune system, focusing specifically on phagocytosis. Learn about the roles of phagocytes, the steps involved in engulfing pathogens, and the mechanisms used to eliminate microbes.