Pattern Recognition Receptors (PRRs) - Online Tutor, Practice Problems & Exam Prep

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

In this video, we're going to begin our lesson on pattern recognition receptors or PRRs. So pattern recognition receptors are commonly abbreviated as PRRs. These pattern recognition receptors or PRRs are really just cell surface receptors of immune cells that are important for sensing and detecting signs of microbial invasion. Moving forward in our course, we'll learn about various types of PRRs, each detecting signs of microbial invasion in different areas of the cell. We'll discuss this more as we progress.

Notice down below, we're showing you our map of the lesson on innate immunity on the left-hand side. We've already discussed the first line defenses, the second line defenses, and cells of innate immunity in our previous lesson videos. We've also started talking about the scanning systems that are important for detecting signs of microbes, serving somewhat as security cameras. Now, we're focusing on these pattern recognition receptors.

Going forward, we will cover several types of pattern recognition receptors, including Toll-like receptors or TLRs, C-type lectin receptors or CLRs, NOD-like receptors or NLRs, and RIG-like receptors or RLRs. We'll discuss all these types thoroughly in upcoming sessions.

All these pattern recognition receptors are crucial for detecting signs of microbial invasion, but in different areas. Some PRRs are found on the cell surface, vital for detecting microbial components on the outside of the cell. Other PRRs are embedded in the membranes of phagosomes and endosomes, which are membranes brought into the cell either through endocytosis or phagocytosis. Here we have a phagosome, resulting from phagocytosis, with embedded PRRs important for detecting ingested microbial components.

Similarly, some PRRs detect components on the outside of the cell, while others detect components that have been ingested by the cell. Lastly, some PRRs located in the cell's cytoplasm are crucial for detecting microbial components and damage inside the cell.

We will discuss these different types of PRRs, their locations, and their detection capabilities as we move forward in our course. This brief introduction to pattern recognition receptors or PRRs concludes here, but we'll learn much more in our upcoming sessions. See you all in our next video.

MAMPs & DAMPs

In this video, we're going to introduce the two terms MAMPs and DAMPs. And so, first, we need to recall from some of our previous lesson videos that immune cells use pattern recognition receptors, or PRRs, to detect different types of signs that will indicate either microbial invasion or host cell damage. Now the term MAMPs is an abbreviation for Microbe-Associated Molecular Patterns. And Microbe-Associated Molecular Patterns, or MAMPs, are going to represent signs of microbes. Now signs of pathogens are referred to as PAMPs, and so, PAMPs are going to be Pathogen-Associated Molecular Patterns. And so, really, the terms MAMPs and PAMPs can be used interchangeably to refer to a broad group of different types of molecules that are associated directly with microbes or pathogens. And so some examples of MAMPs or PAMPs include lipopolysaccharide or LPS, a component found in the outer surface membranes of gram-negative bacteria; peptidoglycan, a molecule specific to bacterial cell walls; viral nucleic acids; fungal cell walls; and flagellin, a protein component important for bacterial flagella. And so these are all direct signs of microbes or pathogens, and so these are all examples of what could be considered MAMPs or PAMPs. Now DAMPs on the other hand are Damage-Associated Molecular Patterns. And so these are not direct signs of microbes/ Instead, they're more like indirect signs of microbes and pathogens, but they are direct signs that indicate host cell damage. And so these are molecules that actually originate from the host, but they indicate host cell damage. So, for example, it could be perhaps some kind of phospholipid, a component of a host cell membrane or something of that nature. Something that belongs to the host that indicates that the host cells have been damaged. And so, if we take a look at our image down below, what you'll notice is that this is an image showing you a macrophage, which is an immune system cell that has many different types of PRRs, many different types of pattern recognition receptors. And these different types of PRRs can detect either MAMPs or DAMPs in different regions. And so, some notice that some of these PRRs are found on the surface, and so, these are going to be capable of detecting microbe- or pathogen-associated molecular patterns, or MAMPs, on the outside of the cells. And so notice here we're showing you these PRRs that are positioned on the cytoplasmic membrane that are going to be detecting signs of microbes outside the cell. And again, notice that we have lipopolysaccharide, peptidoglycan, and flagellin all being detected by these PRRs on the outside of the cell. And then, notice that we have other types of PRRs that are going to be embedded in the membranes of endosomes or phagosomes, and they can detect MAMPs, like for example viral DNA or viral RNA, or bacterial DNA, that have been ingested by the cell. And we have other PRRs that are cytoplasmic PRRs that can detect either MAMPs or DAMPs. And DAMPs are, again, damage-associated molecular patterns, or just DAMPs. And those are going to detect damage to cellular components. And so, this here concludes our brief introduction to these terms, MAMPs and DAMPs, Molecular Microbe-Associated Molecular Patterns, and Damage-Associated Molecular Patterns. And so we'll be able to apply some of these concepts as we move forward in our course. So I'll see you all in our next video.

Which of the following are PRRs least likely to detect?

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

Toll-Like Receptors

In this video, we're going to introduce Toll-like receptors, or TLRs for short. The most well-characterized type of pattern recognition receptor (PRR) is the Toll-like receptors. Toll-like receptors are commonly abbreviated as TLRs, and these membrane-embedded PRRs are used to detect microbe-associated molecular patterns (MAMPs) outside of the cell or MAMPs that have been ingested by the cell through endocytosis or phagocytosis. The TLRs can either be found in the cell membrane or embedded in the membranes of endosomes and phagosomes, which are membrane vesicles that result from endocytosis or phagocytosis. The TLRs embedded in the cell's cytoplasmic membrane will face outward on the cell surface to detect MAMPs outside the cell. The TLRs in endosomes or phagosomes will face inward to monitor what is engulfed via endocytosis or phagocytosis.

Once a microbial invasion has been detected by a TLR, it can initiate an immune response, such as the release of cytokines. Notice in our image below on the left-hand side, we are showing a map of the lesson on the scanning systems of innate immunity, which detects signs of microbes and serves somewhat as security cameras. These pattern recognition receptors help detect microbe-associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs). There are many different types of pattern recognition receptors, but in this video, we are focusing on the Toll-like receptors. These Toll-like receptors are also membrane-embedded and can be found facing towards the outside of the cell to detect signs such as lipopolysaccharide, peptidoglycan, or flagellin, or found inside the membranes of endosomes or phagosomes, facing inwards to detect what has been ingested within the endosome or phagosome. This concludes our brief lesson on Toll-like receptors, and we will learn about other types of pattern recognition receptors as we move forward in our course.

See you all in our next video.

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.

C-Type Lectin Receptors

This video, we're going to introduce the C-type lectin receptors or CLRs. Another type of pattern recognition receptor (PRR) located on the cell surface is the C-type lectin receptors. These C-type lectin receptors, commonly abbreviated as CLRs, are cell surface pattern recognition receptors that bind to carbohydrate MAMPs on microbial surfaces. Some microbes have carbohydrate MAMPs on their surfaces, and these C-type lectin receptors are found on our own immune cells and can bind to the carbohydrate MAMPs found on these microbial surfaces. Lectins themselves, which are found within the name C-type lectin receptor, are proteins that bind to specific carbohydrates. That's really what lectins are.

If we take a look at our image down below, on the left-hand side, we are showing you our map of the lesson on the scanning systems of innate immunity, which serve to detect signs of microbes and serve as, somewhat like security cameras. We are talking about pattern recognition receptors, specifically the C-type lectin receptors. These C-type lectin receptors are membrane-embedded receptors on the cell surface. You'll notice a green region that we refer to as the lectin protein, which is capable of binding to carbohydrates like those found on the microbial surface. Our host cell uses the CLRs to bind and recognize carbohydrate MAMPs found on microbe surfaces. Once the C-type lectin receptor has bound a carbohydrate MAMP on the microbial cell surface, it can then initiate an immune response, such as perhaps the release of some cytokines.

This concludes our brief lesson on C-type lectin receptors or CLRs. We'll be able to apply some of these concepts as we move forward and learn about other pattern recognition receptors. See you in the next video.

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).

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

In this video, we're going to briefly discuss the nucleotide binding and oligomerization domain-like receptors, or in other words, for short, just the Nod-like receptors. These Nod-like receptors are commonly abbreviated as NLRs. Unlike the other two types of pattern recognition receptors that we've talked about in our previous lesson videos, including the toll-like receptors and C-type lectin receptors, which are membrane-bound receptors, the Nod-like receptor is not membrane-bound. Instead, the Nod-like receptor or NLR is a cytoplasmic receptor, meaning that it is not embedded in the membrane and it is dissolved within the cytoplasm. This Nod-like receptor or NLR is a cytoplasmic receptor protein or a cytoplasmic PRR, a cytoplasmic pattern recognition receptor that is going to detect intracellular MAMPs or DAMPs.

These Nod-like receptors, which are cytoplasmic PRRs, play an important role in the immune response of macrophages and dendritic cells. When an NLR detects a MAMP, they can combine with other cytoplasmic proteins to form what is known as an inflammasome. This inflammasome can be defined as a structure that is capable of activating pro-inflammatory cytokine production, leading to inflammation. If we take a look at our image down below, once again on the left-hand side we have our map of the lesson on the scanning systems, and we're focusing specifically on the Nod-like receptors here. Notice that these Nod-like receptors can be found in macrophages and dendritic cells, and that they are cytoplasmic pattern recognition receptors. They are found, dissolved in the cytoplasm. They are not embedded in membranes.

When these Nod-like receptors, or NLRs, bind to MAMPs and DAMPs inside the cell, here's an NLR binding to some kind of MAMP or DAMP, it can lead to the formation of what is known as an inflammasome. The inflammasome will form, which will activate cytokine production. Here we have the inflammasome formation. The formation of the inflammasome will trigger the release of cytokines, and those cytokines can trigger inflammation. Inflammation is an entire response that can help to eliminate the microbes that are causing problems. What you can see here is that these Nod-like receptors are again cytoplasmic PRRs that detect signs of intracellular MAMPs and DAMPs and can lead to some response that can ultimately help to eliminate those microbes or pathogens. This here concludes our brief lesson on the Nod-like receptors or NLRs, and we'll be able to get some practice applying some of these concepts. Then we'll talk about the final type of pattern recognition receptor, the RIG-like receptor. So, I'll see you all in our next lesson video.

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.

Retinoic acid Inducible Gene (RIG)-Like Receptors

In this video, we're going to briefly discuss retinoic acid inducible gene-like receptors, or for short, RIG-like receptors. Now these RIG-like receptors are a second type of cytoplasmic PRR in addition to the Nod-like receptors that we talked about in some of our previous lesson videos. And so once again these RIG-like receptors are cytoplasmic PRRs that are capable of detecting cytoplasmic mAMPs or cytoplasmic microbe-associated molecular patterns. Now, specifically, these RIG-like receptors are cytoplasmic proteins or cytoplasmic PRRs that detect viral RNA. And, these RIG-like receptors that are capable of detecting viral RNA in the cytoplasm are found in most types of host cells.

Now the RIG-like receptors are capable of distinguishing between host cell RNA and viral RNA by 2 features that we have listed down below. The first feature is that viral RNA can be double stranded, and double stranded RNA is quite unique and really only found in some types of viruses. And host RNA is not double stranded, so that makes it easy to distinguish the host cell's RNA from viral RNA.

Now a second feature that helps distinguish, host RNA from viral RNA is that host cell RNA is going to have a 5' cap, as well as a poly A tail, a 3' poly A tail. However, viral RNA does not have a 5' cap or a poly A tail. And so that is another way to distinguish between host cell RNA and viral RNA.

And so if we take a look at our image down below over here on the left-hand side, notice we have our map of the lesson on the scanning systems of innate immunity, which serve to detect signs of microbes and host cell damage, and they serve somewhat as these security cameras. And so here in this video we're focusing specifically on pattern recognition receptors, specifically these RIG-like receptors. And so, these RIG-like receptors, again are capable of detecting viral RNA. And so when a virus infects a cell, so here we have an infecting virus, it will uncoat and release its genetic material, and that viral genetic material can be transcribed through the process of transcription to make viral RNA, either viral single stranded RNA or viral double stranded RNA.

And so, regardless if it's viral single stranded RNA or viral double stranded RNA, the RIG-like receptors, which are down below right here, are capable of distinguishing the host cell's RNA, which notice the host cell's RNA is over here. It is single stranded, and it has a 5' cap and a poly A tail, from the viral RNA. And so, that's because, again, the viral RNA is not going to have the 5' cap or poly A tail, and also viral RNA can be double stranded. And so these RIG-like receptors will detect these viral RNA molecules, and upon detecting the viral RNA molecules, it could initiate some kind of immune response. Like for example, the release of a cytokine, perhaps an interferon for example, which we'll get to talk about the interferon response in more detail later in our course. But for now, this here concludes our brief lesson on these RIG-like receptors, and we'll be able to get some practice applying these concepts as we move forward in our course. So I'll see you all in our next video.

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.

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.

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.

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.

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.

Here’s what students ask on this topic:

What are Pattern Recognition Receptors (PRRs) and why are they important 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). PRRs are essential for initiating immune responses, such as the release of cytokines, which help in 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 detects microbial components in different cellular locations, ensuring a comprehensive immune surveillance system.

What are the differences between MAMPs and DAMPs in the context of PRRs?

MAMPs (Microbe-Associated Molecular Patterns) and DAMPs (Damage-Associated Molecular Patterns) are two types of signals detected by PRRs. MAMPs, also known as PAMPs (Pathogen-Associated Molecular Patterns), are molecules associated with microbial pathogens, such as lipopolysaccharides, peptidoglycan, and viral nucleic acids. DAMPs, on the other hand, are molecules that originate from host cells and indicate cell damage, such as phospholipids from damaged cell membranes. While MAMPs signal the presence of an infection, DAMPs signal tissue damage, both triggering immune responses to protect the host.

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

Toll-like receptors (TLRs) are a type of PRR that are membrane-embedded and detect MAMPs either on the cell surface or within endosomes and phagosomes. TLRs on the cell surface recognize microbial components like lipopolysaccharides and flagellin, while those in endosomes detect ingested microbial nucleic acids. Upon recognizing MAMPs, TLRs initiate immune responses by activating signaling pathways that lead to the production of cytokines, which are crucial for inflammation and pathogen elimination. This helps the immune system respond quickly to infections.

What role do NOD-like receptors (NLRs) play 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 key role in the immune response of macrophages and dendritic cells. When NLRs detect intracellular MAMPs or DAMPs, they can form inflammasomes, which are structures that activate pro-inflammatory cytokine production, leading to inflammation. This process helps to eliminate intracellular pathogens and damaged cells, contributing to the overall immune defense.

How do RIG-like receptors (RLRs) distinguish between viral RNA and host RNA?

RIG-like receptors (RLRs) are cytoplasmic PRRs that detect viral RNA. They distinguish viral RNA from host RNA based on two key features: viral RNA can be double-stranded, which is uncommon in host cells, and viral RNA lacks a 5' cap and a 3' poly-A tail, which are present in host RNA. Upon detecting viral RNA, RLRs initiate immune responses, such as the release of cytokines like interferons, which help to combat viral infections by inhibiting viral replication and activating other immune cells.