Complement

Summary

The video discusses the complement system, a crucial yet often overlooked part of the immune response. It highlights the system's evolutionary importance, its role in inflammation and pathogen defense, and its synthesis in the liver. The lecture covers the three complement pathways—classical, alternative, and lectin-binding—that converge on the membrane attack complex (MAC). It emphasizes the system's regulation to prevent excessive inflammation, introduces key components and their nomenclature, and explains the biological activities and diseases associated with complement deficiencies. The talk aims to provide a deeper understanding of complement beyond its pathways.

Takeaways

• 🧬 Complement is a critical, evolutionarily conserved immune system component, even found in fruit flies.
• 🛡️ Complement consists of plasma proteins that mediate inflammation and immune responses, important in autoimmune disorders, cancer, and traumatic injuries.
• 🧪 Complement proteins make up about 7% of all serum protein and are mainly synthesized in the liver.
• 🔬 There are three complement pathways: classical, alternative, and lectin binding, all culminating in the formation of the membrane attack complex (MAC).
• 🧩 Complement proteins are named with 'C' followed by a number in the order they were discovered, not necessarily the order of their function in the pathway.
• ⚙️ The system includes control proteins to regulate activity, ensuring complement activation doesn't cause excessive inflammation or damage.
• ⚛️ The classical pathway uses proteins C1 to C9, while the alternative pathway involves additional factors B, D, and properdin, and the lectin pathway substitutes C1 with mannose-binding lectin.
• 🛠️ The complement system is vital for opsonization, which enhances phagocytosis of pathogens by marking them for immune cells.
• 💥 Complement activation leads to the formation of the MAC, which lyses pathogens, but its primary role is promoting inflammation and immune responses.
• 🧑‍⚕️ Deficiencies in complement proteins or control proteins can lead to diseases, such as repeated infections or autoimmune-like conditions due to improper clearance of antigen-antibody complexes.

Q & A

What is the main function of the complement system?

The main function of the complement system is to mediate important biological activities, primarily inflammation, and work against pathogens. It also plays a role in mediating inflammation even when a pathogen is not present.

How has the complement system been conserved across species?

The complement system is highly conserved and has been maintained across many species, including complex organisms and even down to fruit flies, indicating its essential role in the immune response.

Where are the components of the complement system synthesized?

The components of the complement system are mainly synthesized in the liver, although there is some local tissue synthesis by macrophages.

What is the classical pathway of the complement system?

The classical pathway of the complement system is the first discovered pathway, which involves a series of proteins named C1 through C9 that work in a specific sequence to drive the inflammatory response.

What is the role of opsonization in the complement system?

Opsonization is the process where pathogens are coated with complement proteins like C3b, which enhances the ability of phagocytes to bind and ingest these pathogens, making it easier for the immune system to clear infections.

What are anaphylatoxins and their role in the complement system?

Anaphylatoxins, such as C3a and C5a, are small fragments that interact with basophils and mast cells to release potent inflammatory mediators like histamines. They increase vascular permeability and recruit immune cells to the site of infection or inflammation.

What is the membrane attack complex (MAC) and its function?

The membrane attack complex (MAC) is formed by complement proteins C5b through C9, and its function is to punch holes in the membranes of target cells, leading to cell lysis and death of the pathogen.

How is the complement system regulated to prevent uncontrolled inflammation?

The complement system is regulated by several mechanisms, including the decay of active proteins, the presence of control proteins on cell surfaces, and specific inhibitors like C1 inhibitor, which prevents the activation of the complement cascade.

What is hereditary angioedema and how is it related to the complement system?

Hereditary angioedema is a condition caused by a deficiency in C1 inhibitor, leading to uncontrolled activation of the classical complement pathway, resulting in increased vascular permeability and recurrent episodes of severe swelling (edema).

Why are repeated Neisseria infections associated with deficiencies in C5 through C8?

Repeated Neisseria infections occur in individuals deficient in complement proteins C5 through C8 because these proteins are crucial for forming the membrane attack complex, which is essential for effectively killing Neisseria bacteria.