Activation Pathways of the Complement System - Online Tutor, Practice Problems & Exam Prep

The complement system activates through three pathways: the alternative, lectin, and classical pathways. The alternative pathway is initiated by C3b binding to microbial surfaces, forming C3 convertase, which cleaves C3 into C3a and C3b, leading to inflammation and opsonization. The lectin pathway uses mannose-binding lectins (MBLs) to recognize carbohydrates on pathogens, also forming C3 convertase. The classical pathway relies on antibodies binding to antigens, activating complement proteins to produce C3 convertase. All pathways converge at C3 convertase, amplifying immune responses against pathogens.

Alternative Pathway

This video we're going to begin our lesson on the activation pathways of the complement system. And so first we need to recall from some of our previous lesson videos that the activation of the complement system can occur by one of three different pathways. The first pathway is going to be the alternative pathway. The second pathway is going to be the lectin pathway, and the third pathway is going to be the classical pathway. Now although these three pathways will differ in the initiation of how they activate the complement system, notice that all three of these pathways will all converge at the formation of the enzyme C3 convertase, and the formation of C3 convertase ultimately will allow for the generation of an immune response such as opsonization, microbe cell lysis, or inflammation.

Now moving forward in our course, we're going to talk about each of these three activation pathways of the complement system in their own separate videos, starting with the alternative pathway here in this video. And so the alternative pathway, once again, is a pathway that is capable of activating the complement system. And so the alternative pathway is activated when the complement system protein C3b binds to the surface molecules of invading microbes. And so there's always going to be some low levels of C3b available within the cell, and those low levels of C3b are capable of binding to the surface molecules of invading microbes, and when they bind to surface molecules of invading microbes, they can trigger activation through the alternative pathway. So binding of the C3b will ultimately attract additional complement system proteins to bind, and eventually it will lead to the formation of the enzyme C3 convertase. And once again, we know that C3 Convertase will hydrolyze C3 into C3a, as well as C3b. And again, C3b, after C3 convertase, C3b will be in high levels.

So there will be high levels of C3b after C3 convertase formation. Whereas before C3 convertase formation, C3b levels are going to be low. And so we know that, the formation of high levels of C3a and C3b will lead to the additional steps of the activation cascade, And, this all this pathway can be amplified, by cleaving more C3, to create more C3b that can bind to the microbe. And so, this C3b can bind to more microbe, which ultimately amplifies the pathway and that can amplify the immune responses. And so taking a look at this image down below right here, again we're showing you the complement system, and the complement system can be activated by the alternative pathway, and that leads to the formation of C3 convertase, which is capable of converting C3 into C3b and C3a. C3a leads to inflammation, whereas C3b can lead to opsonization or cell lysis of microbes. And so over here on the right hand side we're showing you that the alternative pathway is specifically going to be activated and triggered by the molecule C3b.

And this complement system fragment C3b is found in low levels, and so it's capable of binding to microbes, And upon C3b binding to the surface of microbes, it will ultimately lead to the formation of C3 convertase, leading ultimately to high levels of C3b and C3a, which can trigger those immune responses. And so really the biggest thing that you should note here about the alternative pathway is that it is triggered by the complement system protein C3b. And so this here concludes our brief lesson on the alternative pathway, and as we move forward we'll get to talk about the other pathways of complement system activation including the lectin pathway and the classical pathway. So I'll see you all in our next video.

The initiation pathways of the complement system result in the formation of C3 convertase and the cleaving of C3 into C3a & C3b. Where does C3b in the alternative pathway come from if C3 convertase has not yet been created?

• A. C3 can spontaneously cleave into C3a and C3b.
• B. C3 convertase can spontaneously form and in turn cleave C3 into C3a and C3b.
• C. Many microbes already have C3b embedded in their plasma membranes.

The alternative pathway resulting in the formation of C3 convertase and the splitting of C3 into C3a and C3b. C3a triggers the inflammatory response. What is the function of C3b created by the alternative pathway?

• A. Opsonization of invading microbes.
• B. Cell lysis of invading microbes.
• C. Binding to invading microbes further stimulating the alternative pathway.
• D. Combing with other complement proteins to form the inflammasome.
• E. A and B.
• F. C and D.
• G. A, B, and C.

Lectin Pathway

In this video, we're going to briefly discuss the lectin pathway, which is the second pathway of activating the complement system. The lectin pathway activates the complement system using pattern recognition molecules that are called mannose-binding lectins. Now, these mannose-binding lectins are commonly abbreviated as MBLs, and so these mannose-binding lectins or MBLs are lectins themselves. Recall from our previous lesson videos that lectins are proteins that bind carbohydrates. And so these mannose-binding lectins or MBLs are lectins that bind to specific arrangements of mannose, which is a specific type of carbohydrate. This mannose carbohydrate is commonly found on bacterial and fungal cell surfaces. These MBLs will bind to the mannose on the cell surface of bacteria and fungi. Now, these bound MBLs will interact with fragments of activated complement proteins, ultimately forming what we call the C₃ convertase enzyme. We know that the C₃ convertase enzyme is going to cleave C₃ into C_3b and C_3a, and that will lead to these immune responses such as inflammation, cell lysis of the microbes, or opsonization. Notice over here on the left-hand side, we're showing you our map of the complement system, and it can be activated by the lectin pathway, which uses these mannose-binding lectins or MBLs. That will ultimately lead to the formation of C₃ convertase as we just discussed.

Over here on the right-hand side, we're showing you the lectin pathway, which again is going to be using these MBLs, these mannose-binding lectins, which again are these proteins that you can see right here in this image that bind to mannose on the surface of microbes. The mannose in this image is being represented by this little green structure. Again, it is found on the surface of microbes, and so when the mannose-binding lectin binds to the mannose, again, it is capable of activating this lectin pathway, ultimately leading to a cascade of events that leads to the formation of C₃ convertase. This here concludes our brief lesson on the lectin pathway and how it activates the complement system using MBLs. We'll be able to get some practice applying these concepts as we move forward, and then we'll get to talk about the classical pathway of complement system activation.

So, I'll see you all in our next video.

Which of the following choices would not be able to stimulate the lectin pathway of the complement system?

• A. Flu virus with lectins found in the viral membrane.
• B. E. coli with mannose found in the bacterium’s cell walls.
• C. Yeast with mannose found in the fungi’s cell walls.

Classical Pathway

In this video, we're going to briefly introduce the classical pathway, which is the 3rd activation pathway of the complement system. This classical pathway is capable of activating the complement system by using antibodies that are created in adaptive immunity. This classical pathway is the whole reason for why the system is called the complement system. This is because although the complement system is considered part of innate immunity, it does complement the adaptive immune responses. That's because antibodies are part of adaptive immune responses, and this classical pathway will use antibodies to activate the complement system.

First, we need to recall a few terms such as the term antigens, which refers to any toxin or foreign substance that induces an antibody immune response, and the term antibody, which refers to Y-shaped proteins that can recognize and bind to an antigen. During the classical pathway, what happens is antibodies that are generated in adaptive immunity will bind to antigens on the surface of microbes. Those antibodies that are bound to the surface of microbes can then interact with other activated complement proteins in a cascade of events that ultimately leads to the formation of the enzyme C₃ convertase.

If we take a look at our image down below over here on the left hand side, notice we're showing you our map of the lesson on the complement system. Again, we're focusing on the activation pathways, specifically the classical pathway. This pathway is going to utilize antibodies created in adaptive immunity. These Y-shaped proteins, these antibodies, will bind to antigens on the surface of microbes, and those bound antibodies will interact to form C₃ convertase. The classical pathway which uses antibodies and complements the adaptive immune system leads to the formation of C₃ convertase, and we know from our previous lesson videos that the enzyme C₃ convertase will cleave the inactive complement system protein C₃ into C₃a and C₃b, and through a cascade of events that will lead to these responses, immune responses such as inflammation, cell lysis of the microbes, and or opsonization.

Over here on the right, we're focusing specifically on this classical pathway. Again, the classical pathway is going to utilize antibodies, these Y-shaped proteins, that are formed in adaptive immunity. These antibodies will bind to antigens on the surface of the microbes. Notice that these microbes that you see down below, they have these antigens on their surface. The antibodies, these Y-shaped proteins right here, that are produced during adaptive immunity, will bind to these antigens. Upon binding to the antigens, these antibodies will interact with a series of other complement system proteins that ultimately leads to the formation of C₃ convertase, and that can lead to eventually these immune responses.

This concludes our brief lesson on the classical pathway and how it goes about activating the complement system. I'll see you all in our next video.

Which of the following is not a mechanism that triggers the complement system?

• A. C3b binding to the surface of invading microbes.
• B. Antibodies binding to antigens found in the surface of invading microbes.
• C. Mannose-binding lectins binding to mannose on the surface of invading microbes.
• D. C3 convertase binding to the surface of invading microbes.

Which of the following initiation pathways of the complement system specially complements and enhances the adaptive immune system?

• A. Lectin pathway.
• B. Classical pathway.
• C. Alternative pathway.
• D. Adaptive pathway.

Which of the following initiation pathways of the complement system specially binds to carbohydrate molecules that are uniquely found on bacterial and fungal cell surfaces?

• A. Lectin pathway.
• B. Classical pathway.
• C. Alternative pathway.
• D. Adaptive pathway.

Here’s what students ask on this topic:

What are the three activation pathways of the complement system?

The complement system can be activated through three distinct pathways: the alternative pathway, the lectin pathway, and the classical pathway. The alternative pathway is initiated by the binding of C3b to microbial surfaces, leading to the formation of C3 convertase, which cleaves C3 into C3a and C3b. The lectin pathway uses mannose-binding lectins (MBLs) to recognize specific carbohydrate patterns on pathogens, also forming C3 convertase. The classical pathway relies on antibodies binding to antigens on the surface of microbes, activating complement proteins to produce C3 convertase. All three pathways converge at the formation of C3 convertase, which amplifies immune responses such as inflammation, opsonization, and cell lysis.

How does the alternative pathway activate the complement system?

The alternative pathway activates the complement system when the complement protein C3b binds to surface molecules of invading microbes. There are always low levels of C3b present in the cell, and when C3b binds to microbial surfaces, it attracts additional complement proteins, leading to the formation of the enzyme C3 convertase. C3 convertase then cleaves C3 into C3a and C3b, increasing the levels of C3b. This amplification can lead to immune responses such as opsonization, microbe cell lysis, and inflammation. The key trigger for the alternative pathway is the binding of C3b to microbial surfaces.

What role do mannose-binding lectins (MBLs) play in the lectin pathway?

Mannose-binding lectins (MBLs) are crucial in the lectin pathway of complement system activation. MBLs are pattern recognition molecules that bind to specific arrangements of mannose, a carbohydrate commonly found on bacterial and fungal cell surfaces. When MBLs bind to mannose on the surface of pathogens, they interact with fragments of activated complement proteins, leading to the formation of C3 convertase. C3 convertase then cleaves C3 into C3a and C3b, triggering immune responses such as inflammation, opsonization, and cell lysis. Thus, MBLs play a key role in recognizing pathogens and initiating the lectin pathway.

How does the classical pathway complement the adaptive immune system?

The classical pathway complements the adaptive immune system by using antibodies generated during adaptive immunity to activate the complement system. Antibodies, which are Y-shaped proteins, bind to antigens on the surface of microbes. These bound antibodies then interact with other activated complement proteins in a cascade of events that lead to the formation of C3 convertase. C3 convertase cleaves C3 into C3a and C3b, resulting in immune responses such as inflammation, opsonization, and cell lysis. This pathway highlights the interplay between innate and adaptive immunity, as the complement system (part of innate immunity) is activated by antibodies (part of adaptive immunity).

What is the significance of C3 convertase in the complement system?

C3 convertase is a crucial enzyme in the complement system, as it is the point where all three activation pathways (alternative, lectin, and classical) converge. C3 convertase cleaves the inactive complement protein C3 into C3a and C3b. C3a plays a role in inflammation, while C3b is involved in opsonization and cell lysis of microbes. The formation of C3 convertase amplifies the complement cascade, leading to a robust immune response against pathogens. Therefore, C3 convertase is essential for the effective functioning of the complement system and the subsequent immune responses.