Complement System Part 2 - Activation of the Complement System

Summary

This video explains the three pathways that activate the complement system, which plays a crucial role in the immune response. The classical pathway is triggered by antibodies binding to antigens, activating complement factors C1, C2, and C4, which then activate C3. The alternative pathway activates C3 through factors B, D, and P binding to microbial surfaces. The lectin pathway, initiated by the protein MBL, binds to carbohydrate patterns on microbes like bacteria and viruses, also activating C3. All pathways lead to opsonization, cytolysis, and degranulation of mast cells, enhancing the immune defense against infections.

Takeaways

• 😀 The complement system plays a crucial role in enhancing the innate immune response to microbes by activating C3, which has multiple functions.
• 😀 C3 activation can enhance immune responses in three ways: acting as an anaphylatoxin, an opsonin, and contributing to the formation of the MAC complex.
• 😀 There are three pathways by which C3 can be activated: the classical pathway, the alternative pathway, and the lectin pathway.
• 😀 The classical pathway starts when antibodies bind to an antigen on a microbe, which activates C1, and subsequently C2 and C4, leading to C3 activation.
• 😀 C2 and C4 are cleaved into smaller fragments (C2a, C2b, C4a, and C4b), and the C2a-C4b complex activates C3.
• 😀 The alternative pathway, discovered after the classical pathway, involves complement factors B, D, and P binding to lipid-carbohydrate complexes on fungi and bacteria.
• 😀 In the alternative pathway, factors B, D, and P bind to microbes, activating Factor C3 and splitting it into C3a and C3b, which also initiate opsonization, cytolysis, and degranulation of mast cells.
• 😀 The lectin pathway involves Manose Binding Lectin (MBL), an acute-phase protein produced by the liver in response to inflammation.
• 😀 MBL binds to specific carbohydrates like manose on the surface of bacteria and viruses, including pathogens like Candida albicans, Influenza, HIV, Streptococcus, and Salmonella.
• 😀 When MBL binds to microbes, it activates C2 and C4, and their cleavage (C2a, C2b, C4a, and C4b) leads to the activation of C3, triggering immune responses such as opsonization, cytolysis, and mast cell degranulation.

Q & A

What is the complement system and why is it important in the immune response?

The complement system is a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear pathogens from an organism. It plays a key role in immune defense through processes such as opsonization, degranulation of mast cells, and cytolysis.

What are the three main pathways of complement activation discussed in the video?

The three main pathways of complement activation are the classical pathway, the alternative pathway, and the lectin pathway.

How does the classical pathway activate C3 in the complement system?

The classical pathway begins when the variable region of a pair of antibodies binds to an antigen on a microbe. This complex activates C1, which in turn activates C2 and C4. C2 is split into C2a and C2b, and C4 is split into C4a and C4b. C2a and C4b then combine to form an enzyme that cleaves C3 to activate it.

What are the roles of the fragments C3a and C3b once C3 is activated?

Once C3 is activated, C3a acts as an anaphylatoxin, initiating degranulation of mast cells, while C3b acts as an opsonin, marking pathogens for phagocytosis, and also contributes to cytolysis through the formation of the Membrane Attack Complex (MAC).

What distinguishes the alternative pathway from the classical pathway?

The alternative pathway is distinguished by its lack of involvement of antibodies. Instead, it relies on complement factors B, D, and P (properdin) to bind to lipid-carbohydrate complexes on fungi and certain bacteria, activating C3.

How does the lectin pathway initiate complement activation?

The lectin pathway is initiated when lectins like Mannose-Binding Lectin (MBL) bind to specific carbohydrates, such as mannose, on the surface of bacteria and viruses. This triggers the activation of C2 and C4, which ultimately leads to the activation of C3.

What is the function of Mannose-Binding Lectin (MBL) in the complement system?

MBL is an acute-phase protein produced by the liver during inflammation. It acts as an opsonin and activates the complement system by binding to specific carbohydrates, such as mannose, found on the surface of pathogens like bacteria and fungi.

What triggers the liver to produce Mannose-Binding Lectin (MBL)?

The production of MBL is triggered by cytokines released from macrophages and neutrophils during an inflammatory response. These cytokines stimulate the liver to release MBL into the bloodstream.

What are some examples of pathogens that Mannose-Binding Lectin (MBL) targets?

MBL targets a variety of pathogens, including the fungus *Candida albicans*, which causes yeast infections, and viruses such as influenza and HIV, as well as bacteria like *Streptococcus pyogenes* (causing strep throat) and *Salmonella* (associated with foodborne illness).

What is the role of the C3 activation in the immune response?

Activated C3 plays a central role in the immune response by enhancing opsonization (coating pathogens for easier recognition by immune cells), promoting cytolysis (destruction of pathogens through the formation of the Membrane Attack Complex), and facilitating degranulation of mast cells to release inflammatory mediators.