Complement System – An Introduction

Summary

This video explains the complement system, a key component of the immune response that helps defend against pathogens like bacteria, viruses, fungi, and parasites. It focuses on two main activation pathways: the classical and alternative pathways. The classical pathway is triggered by antibody-antigen complexes, while the alternative pathway is activated by bacterial lipopolysaccharides. Both pathways lead to the formation of the membrane attack complex (MAC), which disrupts pathogen cell membranes. The video highlights the cascade of proteolytic events, the biological roles of complement fragments like C3a and C5a, and the system's crucial role in immune defense.

Takeaways

• 😀 The complement system is an essential part of the innate immune response, responsible for eliminating pathogens like bacteria, viruses, fungi, and parasites.
• 😀 The system is composed of over 30 proteins, most found in serum, with others membrane-bound or receptors involved in activation.
• 😀 The classical pathway of the complement system is typically triggered by antigen-antibody complexes, specifically by IgM or IgG antibodies.
• 😀 The activation of the classical pathway starts when C1 binds to the Fc region of an antibody, leading to a cascade of enzymatic actions.
• 😀 Activated C1 cleaves C4 into C4a and C4b, with C4b attaching to the antigen-antibody complex and binding C2, leading to the formation of the C3 convertase.
• 😀 The C3 convertase cleaves C3 into C3a and C3b, with C3b attaching to the convertase to form C5 convertase.
• 😀 C5 convertase cleaves C5 into C5a and C5b, with C5a acting as a chemoattractant for immune cells like mast cells, basophils, and neutrophils.
• 😀 The membrane attack complex (MAC) is a key part of the terminal complement pathway, formed by C5b, C6, C7, C8, and C9, leading to cell lysis.
• 😀 The alternative pathway is continuously active at low levels, triggered by spontaneous hydrolysis of C3, and is amplified by the presence of activating surfaces such as bacterial cells.
• 😀 The alternative pathway also forms C3 convertase, which cleaves C3 and generates C3b, contributing to the formation of C5 convertase and, ultimately, the MAC, leading to pathogen lysis.

Q & A

What is the main role of the complement system in the immune response?

The complement system plays a major role in the innate immune response by aiding in the killing and clearance of invading pathogens, including bacteria, viruses, fungi, and parasites.

What are the two main pathways of complement activation discussed in the script?

The two main pathways of complement activation discussed are the classical pathway and the alternative pathway.

How is the classical pathway of the complement system activated?

The classical pathway is typically activated by antigen-antibody complexes. Activation occurs when the C1 protein binds to the FC portion of an antibody that is bound to an antigen.

What is the role of C1 in the classical pathway?

C1 is the first protein in the classical pathway. It binds to the FC portion of the antibody, triggering a conformational change and leading to the activation of C1r and C1s proteins.

What is the function of the C3 convertase in the classical pathway?

The C3 convertase in the classical pathway, formed by the complex of C4b and C2a, cleaves C3 into C3a and C3b, initiating downstream biological functions of the complement system.

What is the significance of C5 in the classical and alternative pathways?

In both the classical and alternative pathways, C5 is cleaved into C5a and C5b. C5a acts as a potent chemoattractant, while C5b participates in the formation of the membrane attack complex (MAC).

How do C3a and C5a contribute to immune responses?

C3a and C5a are chemoattractants that help recruit immune cells like mast cells, macrophages, and neutrophils to sites of complement activation. They also induce degranulation of mast cells and basophils, releasing histamine and other vasoactive substances.

What is the membrane attack complex (MAC) and how is it formed?

The MAC is a structure formed through the terminal complement pathway, beginning with C5b associating with C6, C7, and C8. This complex disrupts the cell membrane, and the addition of C9 molecules forms a pore large enough to cause cell lysis.

How is the alternative pathway activated?

The alternative pathway is activated by lipopolysaccharides (LPS) and other components on the surface of pathogens. It is always active at low levels due to the spontaneous hydrolysis of C3, forming C3b that interacts with Factor B.

What is the amplification effect in the alternative pathway?

The alternative pathway exhibits an amplification effect where C3b generated from the initial complement activation binds to the activating surface and further amplifies the complement cascade, leading to rapid accumulation of C3b molecules on the pathogen surface.