Review of the Complement System: Study with Video Lessons, Practice Problems & Examples

The complement system is a crucial part of innate immunity, activated through three pathways: the alternative, lectin, and classical pathways. Activation leads to the formation of C3 convertase, which cleaves the inactive protein C3 into C3a and C3b. C3a triggers inflammation, while C3b enhances opsonization, improving phagocytosis. Additionally, C3b contributes to the formation of membrane attack complexes, leading to cell lysis of pathogens. This interplay between innate and adaptive immunity highlights the complement system's role in immune responses against invading microbes.

Review of the Complement System

In this video, we're going to do a review of the complement system. And so, because this video is a review, what that means is that there's really no new information here in this video. And so, if you're already feeling really good about the complement system then you can feel free to skip this video. But if you're looking for a good way to review a lot of the concepts that we talked about in our previous lesson videos, then stick around because this might be a really helpful review for you. In reviewing the complement system, we're going to review the activation pathways, as well as the responses or the effects of activation of the complement system. Recall that the complement system consists of inactive proteins that are circulating in our blood and circulating through the tissues. These inactive complement system proteins can become activated by one of three different pathways: the alternative pathway, the lectin pathway, or the classical pathway. Now, the alternative pathway will activate the complement system and is triggered by C3b, a complement system fragment, binding to the surface of invading microbes. When C3b binds to the surface of invading microbes, it helps to activate the complement system. Of course, the alternative pathway is going to ultimately lead to the formation of the enzyme C3 convertase, which is actually where all three of these pathways converge together. So, the lectin pathway is going to be triggered and activate the complement system through the MBL, the mannose-binding lectin. The mannose-binding lectin consists of a protein that binds to mannose carbohydrates that are found on the surface of microbes. So they bind to the surface of invading microbes by binding to the mannose on those microbes. Here in this image, notice that the mannose is represented by these little green hexagons that are on the surface of the microbe. The lectin, the mannose-binding lectin or the MBL, is represented by this structure that you see here. When the mannose-binding lectin binds to the mannose on the surface of the microbes, it will lead to a cascade of events that ultimately leads to the formation of C3 convertase. Then, the classical pathway is going to be triggered and activate the complement system when antibodies from the adaptive immune system are going to bind to antigens on the surface of microbes. Ultimately, these antibodies from the adaptive immune system that bind to the surface of these microbes lead to a cascade of events that once again leads to the formation of C3 convertase. This classical pathway here has an asterisk next to it because the classical pathway is really why the complement system is called the complement system. Because through the classical pathway, the complement system, which is part of innate immunity, is able to complement the adaptive immunity. That's because the antibodies are part of adaptive immunity, and the antibodies help to trigger the complement system, which is part of innate immunity. There's some crosstalk between innate immunity and adaptive immunity right here through the classical pathway. But regardless of which pathway is used, the alternative lectin or classical pathway, they all lead to the formation of C3 convertase, which is an enzyme that is being represented as scissors here because this enzyme C3 convertase will cleave or fragment this inactive complement system protein called C3. When C3 is cleaved by C3 convertase, it will be cleaved into C3a, which is over here, as well as C3b, which is over here. And so there will be high levels of C3a and high levels of C3b after the formation of C3 convertase. Now, the C3a, along with other complement system proteins such as, for example, C5a, can go on to trigger the inflammatory response to help eliminate microbes. And C3b can go on to act as an opsonin to allow for opsonization, which is going to improve the effectiveness of phagocytosis, allowing phagocytes like macrophages to phagocytose microbes much easier and much more effectively. And C3b can also interact with a series of other complement system proteins to lead to microbe cell lysis through the formation of membrane attack complexes that form pores in the membranes of gram-negative bacteria, such as these bacteria being shown here. And so this here concludes our review of the complement system, and we'll be able to apply some of the concepts that are in this review as we move forward. So I'll see you all in our next video.

Which of the following statements about the complement system is true?

• A. There are many methods of triggering the complement system.
• B. There are many immune responses triggered by the complement system.
• C. All triggers of the complement system lead to the formation of C3 convertase.
• D. C3a and C3b result in different immune response for the complement system.
• E. All of the above are true.

Which complement molecule is an attractant for neutrophils?

• A. C4b.
• B. C5a.
• C. C3b.
• D. C7a.

The key molecule upon which all complement pathways converge is

• A. C1.
• B. C2.
• C. C3.
• D. C6.

The complex resulting from complement activity that leads to cell lysis is the

• A. Prostaglandin complex.
• B. Leukotriene activating complex.
• C. Membrane attack complex.
• D. Histamine complex.

Which of the following are most susceptible to complement lysis?

• A. Gram-positive bacteria.
• B. Gram-negative bacteria.
• C. Bacteriophages.
• D. Prions.

Here’s what students ask on this topic:

What are the three pathways that activate 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 triggered by the binding of C3b to the surface of invading microbes. The lectin pathway is activated when mannose-binding lectin (MBL) binds to mannose carbohydrates on the surface of microbes. The classical pathway is initiated when antibodies from the adaptive immune system bind to antigens on the surface of microbes. All three pathways ultimately lead to the formation of C3 convertase, which cleaves the inactive protein C3 into C3a and C3b, playing crucial roles in immune responses.

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

C3 convertase is a crucial enzyme in the complement system that cleaves the inactive protein C3 into two fragments: C3a and C3b. C3a plays a role in triggering the inflammatory response, which helps to eliminate microbes. C3b acts as an opsonin, enhancing opsonization and improving the effectiveness of phagocytosis by phagocytes like macrophages. Additionally, C3b interacts with other complement proteins to form membrane attack complexes, leading to the lysis of pathogen cells. Thus, C3 convertase is essential for amplifying the immune response against invading microbes.

How does the classical pathway of the complement system complement adaptive immunity?

The classical pathway of the complement system complements adaptive immunity by involving antibodies from the adaptive immune system. When these antibodies bind to antigens on the surface of microbes, they trigger a cascade of events that lead to the formation of C3 convertase. This interaction between antibodies (adaptive immunity) and the complement system (innate immunity) enhances the overall immune response. The classical pathway exemplifies the crosstalk between innate and adaptive immunity, making the immune system more effective in combating pathogens.

What are the effects of C3a and C3b in the complement system?

C3a and C3b, produced by the cleavage of C3 by C3 convertase, have distinct roles in the complement system. C3a is involved in triggering the inflammatory response, which helps to recruit immune cells to the site of infection and eliminate microbes. C3b acts as an opsonin, enhancing opsonization and making it easier for phagocytes like macrophages to engulf and destroy pathogens. Additionally, C3b contributes to the formation of membrane attack complexes, which create pores in the membranes of pathogens, leading to their lysis and death.

What is the significance of the membrane attack complex in the complement system?

The membrane attack complex (MAC) is a crucial component of the complement system that leads to the lysis of pathogen cells. Formed by the interaction of C3b with other complement proteins, the MAC creates pores in the membranes of gram-negative bacteria and other pathogens. These pores disrupt the integrity of the microbial cell membrane, causing cell lysis and death. The formation of the MAC is an essential mechanism by which the complement system directly eliminates invading microbes, thereby protecting the host from infections.