Pattern Recognition Receptors (PRRs): Videos & Practice Problems

Pattern recognition receptors (PRRs) are crucial for immune cells to detect microbial invasion and host cell damage. Key types include Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), and RIG-like receptors (RLRs). TLRs and CLRs identify microbe-associated molecular patterns (MAMPs) on cell surfaces, while NLRs and RLRs detect intracellular MAMPs and damage-associated molecular patterns (DAMPs). This detection initiates immune responses, such as cytokine release, essential for inflammation and pathogen elimination.

Pattern Recognition Receptors

Pattern recognition receptors (PRRs) are essential components of the immune system, functioning as cell surface receptors on immune cells that detect signs of microbial invasion. These receptors play a crucial role in identifying pathogens and initiating immune responses. There are various types of PRRs, each specialized for detecting microbial components in different cellular locations.

PRRs can be categorized based on their location: some are found on the cell surface, while others are embedded in the membranes of phagosomes and endosomes, or located within the cytoplasm of the cell. Surface PRRs are responsible for recognizing microbial components and signs of cell damage from outside the cell. In contrast, PRRs located in phagosomes and endosomes detect components that have been ingested through processes like endocytosis or phagocytosis. Additionally, cytoplasmic PRRs monitor for microbial components and damage that occur inside the cell.

As we delve deeper into the study of PRRs, we will explore specific types, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), and RIG-like receptors (RLRs). Each of these receptors plays a unique role in the immune response, contributing to the body's ability to recognize and respond to various pathogens effectively.

Understanding the function and location of different PRRs is vital for comprehending how the immune system detects and responds to microbial threats, ultimately enhancing our knowledge of innate immunity.

MAMPs and DMPs

In the study of immunology, understanding the roles of MAMPs and DAMPs is crucial for grasping how the immune system detects threats. MAMPs, or Microbe Associated Molecular Patterns, are molecules that signal the presence of microbes. These patterns are recognized by immune cells through pattern recognition receptors (PRRs). Examples of MAMPs include lipopolysaccharide (LPS), which is found in the outer membranes of gram-negative bacteria, peptidoglycan from bacterial cell walls, viral nucleic acids, fungal cell wall components, and flagellin, a protein associated with bacterial flagella. These molecules serve as direct indicators of microbial presence, often referred to as PAMPs, or Pathogen Associated Molecular Patterns, which can be used interchangeably with MAMPs.

On the other hand, DAMPs, or Damage Associated Molecular Patterns, are indicative of host cell damage rather than direct microbial signs. These molecules originate from the host and signal that cellular injury has occurred. For instance, certain phospholipids from damaged cell membranes can act as DAMPs. The immune system utilizes various PRRs to detect both MAMPs and DAMPs, which are located on the surface of immune cells, within endosomes, or in the cytoplasm. This detection process is vital for initiating appropriate immune responses to both microbial threats and cellular damage.

In summary, MAMPs and DAMPs play essential roles in the immune response, with MAMPs signaling the presence of pathogens and DAMPs indicating host cell damage. Understanding these concepts is fundamental for further exploration of immune system functions and responses.

Which of the following are PRRs least likely to detect?

• A. Glycolysis enzymes.
• B. Peptidoglycan.
• C. Flagellin.
• D. Lipopolysaccharide.
• E. Foreign nucleotide sequences.

Answer: (A)

Toll-Like Receptors (TLRs)

Toll-like receptors (TLRs) are a crucial type of pattern recognition receptor (PRR) that play a significant role in the immune system by detecting microbe-associated molecular patterns (MAMPs). These receptors are embedded in cell membranes and can be found either on the surface of the cytoplasmic membrane or within the membranes of endosomes and phagosomes, which are vesicles formed during endocytosis or phagocytosis.

TLRs on the cell surface are oriented outward to identify MAMPs present outside the cell, while those located in endosomes or phagosomes face inward to monitor substances that have been engulfed. This dual positioning allows TLRs to effectively recognize various microbial components, such as double-stranded RNA, which is indicative of certain viral infections and is not typically found in host cells.

Upon detecting a MAMP, TLRs initiate an immune response, often leading to the release of cytokines, which are signaling molecules that help coordinate the immune response. This mechanism is part of the innate immune system's scanning capabilities, functioning similarly to security cameras that monitor for signs of microbial invasion.

In summary, TLRs are essential for the early detection of pathogens, enabling the immune system to respond swiftly to potential threats. Their ability to recognize a wide range of microbial signatures underscores their importance in maintaining immune surveillance and initiating appropriate defensive actions.

Toll-like receptors (TLRs) bind molecules on pathogens. Why is this helpful to the immune response?

• A. It provides a highly specific response to very small and highly unique areas on an individual pathogenic microbe, providing the most specific and selective response possible.
• B. It provides a general response to broad categories of molecules/cells that should NOT be in our system, as we don't have these molecules on our own cells.
• C. These secreted molecules help bind pathogens and then direct them to receptors on the immune system cells that are best capable of eliminating them from our systems. TLRs are delivery mechanisms for the immune responses.
• D. TLRs are capable of directly lysing (destroying) the microbes, helping our immune responses by eliminating pathogens.

Answer: (B)

C-Type Lectin Receptors (CLRs)

C-type lectin receptors (CLRs) are a vital class of pattern recognition receptors (PRRs) located on the surface of immune cells. These receptors play a crucial role in the immune system by binding to carbohydrate microbe-associated molecular patterns (MAMPs) found on the surfaces of various microbes. The term "lectin" refers to proteins that specifically bind to carbohydrates, which is fundamental to the function of CLRs.

When CLRs recognize and bind to carbohydrate MAMPs, they initiate an immune response. This response can include the release of cytokines, which are signaling molecules that help coordinate the immune response. The structure of CLRs includes a lectin domain, which is responsible for the carbohydrate binding, allowing the immune cells to detect and respond to microbial threats effectively.

In the context of innate immunity, CLRs act like security cameras, constantly scanning for signs of microbial presence. Their ability to recognize specific carbohydrate patterns on pathogens enhances the immune system's capacity to identify and eliminate infections. Understanding the function and mechanism of CLRs is essential as we explore other types of PRRs and their roles in immune responses.

Which of the following is not considered a MAMP (Microbe/Pathogen-Associated Molecular Pattern)?

• A. Carbohydrates on microbial surfaces.
• B. Peptidoglycan from gram + bacteria.
• C. Damaged host cell DNA.
• D. Lipopolysaccharide (LPS).

Answer: (C)

Nucleotide-Binding & Oligomerization Domain (NOD)-Like Receptors

Nucleotide binding and oligomerization domain-like receptors, commonly known as NLRs, are a crucial type of cytoplasmic pattern recognition receptor (PRR) that play a significant role in the immune response. Unlike toll-like receptors and C-type lectin receptors, which are membrane-bound, NLRs are located within the cytoplasm, allowing them to detect intracellular microbe-associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs).

When NLRs identify MAMPs or DAMPs, they can oligomerize with other cytoplasmic proteins to form a complex known as an inflammasome. This inflammasome is essential for activating the production of pro-inflammatory cytokines, which are signaling molecules that promote inflammation. The inflammatory response is vital for eliminating pathogens and restoring homeostasis within the body.

In summary, NLRs serve as key cytoplasmic receptors that detect intracellular signals indicative of infection or cellular damage. Their ability to form inflammasomes and trigger cytokine release underscores their importance in the innate immune response, particularly in immune cells such as macrophages and dendritic cells. Understanding the function of NLRs enhances our knowledge of immune system mechanisms and their role in combating infections.

Why are NOD-like receptors (NLRs) important for macrophage cells?

• A. Macrophages commonly ingest infectious material and use NLRs to detect intracellular MAMPs.
• B. Macrophages are unstable and commonly have intracellular damage and use NLRs to detect DAMPs.
• C. Macrophages use NLRs to detect MAMPs which triggers the formation of RIG-like receptors.
• D. Macrophages are the only cells able to detect viral infection and use NLRs to detect viral RNA.

Answer: (A)

Retinoic Acid Inducible Gene (RIG)-Like Receptors

Retinoic acid inducible gene-like receptors, commonly known as RIG-like receptors (RLRs), are a crucial type of cytoplasmic pattern recognition receptors (PRRs) that play a significant role in the immune response by detecting viral RNA within host cells. Unlike other PRRs, such as NOD-like receptors, RLRs specifically identify cytoplasmic microbe-associated molecular patterns (mAMPs), particularly those associated with viral infections.

RLRs are found in various host cell types and are adept at distinguishing between host cell RNA and viral RNA based on two key characteristics. First, viral RNA can exist as double-stranded RNA, a form that is relatively rare and primarily associated with certain viruses. In contrast, host cell RNA is typically single-stranded. Second, host RNA is characterized by the presence of a 5' cap and a 3' poly-A tail, which are absent in viral RNA. This distinction allows RLRs to effectively identify and respond to viral infections.

When a virus infects a cell, it releases its genetic material, which can be transcribed into either single-stranded or double-stranded viral RNA. RLRs recognize these viral RNA molecules, triggering an immune response that may include the release of cytokines, such as interferons. These cytokines play a vital role in the antiviral response, helping to establish an effective defense against the invading virus.

In summary, RIG-like receptors serve as essential components of the innate immune system, acting as sensors that detect viral RNA and initiate protective immune responses. Understanding the function and mechanisms of RLRs is fundamental to comprehending how the immune system identifies and combats viral infections.

What defining features of viral RNA allows the RIG-like receptors to distinguish infecting viral RNA from the host cell’s RNA?

• A. Viral RNA has a 5’ cap while host cell RNA does not.
• B. Viral RNA has a poly-A tail while host cell RNA does not.
• C. Viral RNA can be double stranded while host cell RNA is single stranded.
• D. Viral RNA has a circular formation while host cell RNA is linear.
• E. None of the above.

Answer: (C)

In addition to peptidoglycan, which molecule(s) unique to bacteria would PRRs recognize?

• A. Lipopolysaccharide (LPS).
• B. Fungal cell walls.
• C. Flagellin proteins.
• D. Tubulin proteins found in cilia.
• E. A and C.
• F. B and D.
• G. All of the answers would be recognized by PRRs.

Answer: (E)

Toll-like receptors are receptor proteins on ___________.

• A. Granulocytes that destroy parasitic helminths.
• B. Phagocytes that recognize foreign or microbe-associated molecules.
• C. Viruses entering the body which stimulate the immune system.
• D. Mucus producing cells that trigger mucus production when they bind with an allergen.

Answer: (B)

Which type of pattern recognition receptor when bound to MAMPs triggers the formation of the inflammasome?

• A. NOD-Like Receptors.
• B. RIG-Like Receptors.
• C. Toll-Like Receptors.
• D. C-Type Lectin Receptors.

Answer: (A)

Toll-like receptors:

• A. Are cytokines.
• B. Each recognize a specific "danger" molecule.
• C. Are embedded in cellular membranes.
• D. Are part of adaptive immunity.
• E. b and c.

Answer: (E)

______ on phagocytes bind to PAMPs on bacteria, triggering uptake & destruction of the bacterial pathogens?

• A. PRRs.
• B. PAMPs.
• C. AMPs.
• D. PMNs.

Answer: (A)

Here’s what students ask on this topic:

What are Pattern Recognition Receptors (PRRs) and their role in the immune system?

Pattern Recognition Receptors (PRRs) are cell surface receptors found on immune cells that play a crucial role in detecting microbial invasion and host cell damage. They recognize specific molecular patterns associated with pathogens (MAMPs) or host cell damage (DAMPs). Upon detection, PRRs initiate immune responses, such as cytokine release, which are essential for inflammation and pathogen elimination. Key types of PRRs include Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), and RIG-like receptors (RLRs). Each type of PRR is specialized to detect microbial components in different cellular locations, ensuring a comprehensive immune surveillance system.

What are the different types of Pattern Recognition Receptors (PRRs) and their functions?

There are several types of Pattern Recognition Receptors (PRRs), each with specific functions:

• Toll-like receptors (TLRs): Membrane-bound receptors that detect MAMPs on the cell surface or within endosomes/phagosomes.
• C-type lectin receptors (CLRs): Cell surface receptors that bind to carbohydrate MAMPs on microbial surfaces.
• NOD-like receptors (NLRs): Cytoplasmic receptors that detect intracellular MAMPs and DAMPs, leading to inflammasome formation and cytokine release.
• RIG-like receptors (RLRs): Cytoplasmic receptors that detect viral RNA, distinguishing it from host RNA, and initiate antiviral responses.

These PRRs collectively ensure the immune system can detect and respond to a wide range of microbial invasions and cellular damage.

How do Toll-like receptors (TLRs) function in the immune response?

Toll-like receptors (TLRs) are membrane-bound PRRs that detect MAMPs either on the cell surface or within endosomes/phagosomes. TLRs on the cell surface recognize microbial components like lipopolysaccharides and flagellin, while those in endosomes/phagosomes detect ingested microbial nucleic acids. Upon recognizing MAMPs, TLRs initiate immune responses by activating signaling pathways that lead to the production of cytokines and other inflammatory mediators. This helps to recruit and activate other immune cells, enhancing the body's ability to eliminate pathogens and initiate an effective immune response.

What are MAMPs and DAMPs, and how do they relate to PRRs?

MAMPs (Microbe-Associated Molecular Patterns) and DAMPs (Damage-Associated Molecular Patterns) are molecular signals detected by PRRs. MAMPs are molecules associated with microbial pathogens, such as lipopolysaccharides, peptidoglycan, and viral nucleic acids. DAMPs, on the other hand, are molecules released from damaged host cells, indicating cellular injury. PRRs, such as TLRs, CLRs, NLRs, and RLRs, recognize these patterns and trigger immune responses. MAMPs and DAMPs help the immune system distinguish between microbial invaders and host cell damage, ensuring appropriate and targeted immune reactions.

What is the role of NOD-like receptors (NLRs) in the immune system?

NOD-like receptors (NLRs) are cytoplasmic PRRs that detect intracellular MAMPs and DAMPs. Unlike membrane-bound PRRs, NLRs are dissolved in the cytoplasm and play a crucial role in the immune response of macrophages and dendritic cells. Upon detecting MAMPs or DAMPs, NLRs can form inflammasomes, which are protein complexes that activate pro-inflammatory cytokine production. This leads to inflammation, a critical response for eliminating pathogens and repairing tissue damage. NLRs thus help in recognizing intracellular threats and initiating appropriate immune responses.