2 Sistem Komplemen Alternative and Lectin

Summary

This transcript discusses the immune system's complex complement activation pathways, specifically the classical, alternative, and lectin pathways. It explains how these pathways initiate immune responses, regulate inflammation, and involve enzymes, proteins, and their interactions. Key concepts like proteolysis, cascade mechanisms, and the formation of membrane attack complexes are explored in detail. The script also touches on the importance of regulatory factors in controlling these pathways to prevent continuous activation and tissue damage, as well as the role of opsonization in immune recognition and phagocytosis.

Takeaways

• 😀 The complement cascade mechanism involves several stages, where each stage processes the output of the previous one.
• 😀 The classical pathway is initiated when specific signals activate proteolytic enzymes, such as C1q, which helps in the formation of complexes.
• 😀 Cascade mechanisms have built-in regulation to prevent continuous activation, which could otherwise cause inflammation and tissue damage.
• 😀 The C1 complex and its regulators, such as C1s and C1r, ensure that activation only occurs when necessary, preventing undesired effects.
• 😀 In the classical pathway, C4-binding proteins act as regulators, preventing the inappropriate binding of C4 components to form the C3 convertase complex.
• 😀 The alternative pathway is initiated by spontaneous hydrolysis of C3, or through interactions with microbial components, triggering a different activation process.
• 😀 In the alternative pathway, C3b can directly interact with factors like B and D, forming the alternative C3 convertase complex that is crucial for amplification.
• 😀 Lectin pathway operates similarly to the classical pathway but is triggered by the binding of mannose-binding lectin (MBL) to microbial carbohydrates, without requiring antibodies.
• 😀 The lectin pathway leads to the activation of C3 and C5 convertases, similar to the classical pathway, resulting in membrane attack complex (MAC) formation.
• 😀 The biological effects of complement activation include opsonization (enhancing phagocytosis), degranulation of mast cells, and increased vascular permeability, contributing to inflammation.

Q & A

What is the cascade mechanism mentioned in the transcript?

The cascade mechanism refers to a process involving multiple stages, where each stage processes the output of the previous one. It is commonly seen in proteolytic mechanisms, which involve the activity of proteolytic enzymes to regulate the progression of the reaction.

Why is regulation important in cascade mechanisms?

Regulation is crucial to prevent the cascade from being continuously active. Continuous activation could lead to inflammation and tissue damage. The system is designed to activate only when certain signals or initiators are present.

What are the roles of the proteins C1s, C1r, and C1NH?

C1s and C1r are enzymes involved in the initial activation of the classical complement pathway. C1NH, on the other hand, acts as an inhibitor to regulate C1 activation by disrupting the association of C1s and C1r, preventing the cascade from proceeding further.

What is the significance of C4-binding protein in the classical pathway?

C4-binding protein prevents the formation of the C3 convertase complex by binding to C4b. This binding stops the progression of the cascade, preventing overactivation and ensuring proper immune response.

How does the alternative pathway differ from the classical pathway?

The alternative pathway initiates through spontaneous hydrolysis of C3, which then interacts with factor B to form C3 convertase. Unlike the classical pathway, the alternative pathway does not require antibody interaction and is considered part of the innate immune system.

What role does the lectin pathway play in complement activation?

The lectin pathway is triggered when mannose-binding lectin (MBL) binds to carbohydrate patterns on the surface of pathogens. This interaction activates MASP-1 and MASP-2 proteases, which then activate the complement system similarly to the classical pathway but without involving antibodies.

What is opsonization, and why is it important in immune response?

Opsonization is the process by which complement proteins or antibodies bind to pathogens, marking them for easier recognition and phagocytosis by immune cells. It enhances the ability of phagocytes to identify and engulf pathogens.

How do complement proteins interact with mast cells and basophils?

Complement proteins can bind to receptors on mast cells and basophils, causing them to degranulate and release histamine. This release contributes to the inflammatory response by increasing vascular permeability and attracting other immune cells to the site of infection.

What triggers the spontaneous hydrolysis of C3 in the alternative pathway?

Spontaneous hydrolysis of C3 can occur due to the presence of water in the system. This hydrolyzed form of C3 (C3H2O) can then interact with factor B, initiating the alternative pathway.

How does the regulation of complement activity prevent excessive inflammation?

Regulation of complement activity, such as through the actions of regulatory proteins like C1NH, C4-binding protein, and factor H, ensures that complement activation only occurs when necessary and is terminated promptly to prevent excessive inflammation and tissue damage.