Activation Pathways of the Complement System: Videos & Practice Problems

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

The complement system is a crucial part of the immune response, and its activation can occur through three distinct pathways: the alternative pathway, the lectin pathway, and the classical pathway. Despite their different initiation mechanisms, all three pathways converge at the formation of the enzyme C3 convertase, which plays a vital role in generating immune responses such as opsonization, microbe cell lysis, and inflammation.

Focusing on the alternative pathway, it is activated when the complement protein C3b binds to the surface molecules of invading microbes. C3b is typically present in low levels within the body, but its binding to microbial surfaces triggers the activation of the complement system. This binding attracts additional complement proteins, leading to the formation of C3 convertase.

Once C3 convertase is formed, it hydrolyzes C3 into two fragments: C3a and C3b. The levels of C3b increase significantly after the formation of C3 convertase, amplifying the immune response. The high levels of C3a contribute to inflammation, while C3b is essential for opsonization, which enhances phagocytosis, and for the lysis of microbial cells.

The amplification of the alternative pathway occurs as more C3 is cleaved, producing additional C3b that can bind to more microbes, thereby intensifying the immune response. This cascade effect is crucial for effectively combating infections.

In summary, the alternative pathway is primarily triggered by the binding of C3b to microbial surfaces, leading to the formation of C3 convertase and the subsequent increase in C3a and C3b levels, which are essential for a robust immune response. Future discussions will explore the lectin and classical pathways of complement system activation.

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.

Answer: (A)

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.

Answer: (G)

Lectin Pathway

The lectin pathway is a crucial mechanism for activating the complement system, which plays a significant role in the immune response. This pathway utilizes pattern recognition molecules known as mannose-binding lectins (MBLs). MBLs are a type of lectin, which are proteins that specifically bind to carbohydrates. In this case, MBLs target mannose, a carbohydrate commonly found on the surfaces of bacteria and fungi.

When MBLs bind to mannose on microbial surfaces, they initiate a series of interactions with activated complement proteins. This interaction leads to the formation of the C3 convertase enzyme, a key component in the complement activation cascade. The C3 convertase cleaves the complement protein C3 into two fragments: C3b and C3a. This cleavage is essential for triggering various immune responses, including inflammation, cell lysis of pathogens, and opsonization, which enhances the ability of phagocytes to engulf and destroy microbes.

In summary, the lectin pathway, through the action of mannose-binding lectins, activates the complement system by forming C3 convertase. This process is vital for the immune system's ability to recognize and respond to infections caused by bacteria and fungi. Understanding this pathway lays the groundwork for further exploration of the classical pathway of complement activation, which will be discussed in subsequent lessons.

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.

Answer: (A)

Classical Pathway

The classical pathway is the third activation pathway of the complement system, which plays a crucial role in the immune response. This pathway is unique because it relies on antibodies produced during adaptive immunity to activate the complement system. While the complement system is primarily part of innate immunity, it enhances the adaptive immune responses, hence the name "complement."

To understand the classical pathway, it's essential to define a couple of key terms. Antigens are foreign substances, such as toxins, that trigger an immune response, while antibodies are Y-shaped proteins that specifically recognize and bind to these antigens. In the classical pathway, antibodies bind to antigens present on the surface of microbes. This binding initiates a cascade of interactions with other activated complement proteins, ultimately leading to the formation of the enzyme C3 convertase.

The formation of C3 convertase is a pivotal step in the complement activation process. This enzyme cleaves the inactive complement protein C3 into two fragments: C3a and C3b. The cleavage of C3 is significant as it triggers various immune responses, including inflammation, cell lysis of pathogens, and opsonization, which enhances the ability of phagocytes to engulf and destroy microbes.

In summary, the classical pathway utilizes antibodies from adaptive immunity to bind to microbial antigens, leading to the activation of the complement system through the formation of C3 convertase. This process is vital for mounting effective immune responses against infections.

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.

Answer: (D)

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.

Answer: (B)

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.

Answer: (A)

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.