Ch 3 -Humoral Immunity III: The Complement System

Complement System

A group of approximately 15 plasma proteins that interact to produce physiological effects, and are part of the innate immune mechanisms.

Activation of Complement Proteins

When components are activated, they possess enzyme activity and are designated with a line over the number of the component.

C3 Convertase

A powerful serine protease formed by the combination of C4b and C2a in the classical pathway, which splits C3 into C3a and C3b.

C3b

A complement protein that initiates the alternative pathway and can bind to an activator or unprotected surface to activate the complement system.

Opsonization

The process by which complement components coat microbes, enhancing phagocytosis.

C5 Convertase

A complex formed in both the classical (C4b2a3b) and alternative pathways that cleaves C5 into C5a and C5b.

Classical Pathway

A complement activation pathway triggered by antigen-antibody complexes, characterized by specific interactions between complement proteins.

Alternative Pathway

A more primitive complement activation pathway triggered by microbial cell walls, involving components such as Factor B.

Anaphylatoxins

Complement fragments (C3a, C4a, C5a) that can stimulate mast cell release of histamine and serve as chemotactic factors.

Membrane Attack Complex (MAC)

The structure formed at the end of the complement pathway, responsible for creating pores in the membranes of target cells.

What is the Classical Pathway in immunology?

A complement activation mechanism triggered by antigen-antibody complexes.

What initiates the Alternative Pathway?

microbial cell walls without the need for antibodies.

Components of the Complement System

The Complement System consists of approximately 15 plasma proteins that work together to enhance immune responses.

Role of C3 Convertase

C3 Convertase cleaves C3 into C3a and C3b, playing a key role in both classical and alternative pathways.

What triggers C5 Convertase?

C5 Convertase is activated by the actions of the C3 Convertase in both classical and alternative complement pathways.

How does the Complement System enhance phagocytosis?

By opsonization, where complement proteins coat microbes to improve recognition and ingestion by phagocytes.

Function of Membrane Attack Complex (MAC)

The MAC forms pores in the membranes of target cells, leading to cell lysis.

What are Anaphylatoxins?

complement fragments like C3a, C4a, and C5a that stimulate mast cell degranulation.

Significance of Opsonization

Opsonization greatly increases the efficiency of phagocytosis by marking pathogens for destruction.

Key difference between Classical and Alternative Pathways

Classical Pathway requires antibody-antigen interactions while the Alternative Pathway operates independently of antibodies.

The ___ Pathway is initiated by the binding of C1 to antibody-antigen complexes.

Classical

In the Classical Pathway, the complex C4b2a is also known as ___ Convertase.

C3

The ___ Pathway relies on the recognition of microbial surfaces by complement proteins without requiring antibodies.

Alternative

C5 Convertase for the Classical Pathway is represented as ___ .

C4b2a3b

The alternative pathway involves the factor ___ which helps stabilize the C3 convertase.

B

____ is a critical component of both Classical and Alternative pathways that gets cleaved to provide biological effects.

C3

In the Classical Pathway, the activation of C1 leads to cleavage of C4 and C2 forming ___ Convertase.

C3

The ___ Pathway is considered more primitive and is an essential part of the innate immune response.

Alternative

The end product of complement activation is the formation of the ___, which creates pores in target cell membranes.

Membrane Attack Complex (MAC)

Both pathways lead to the production of ___, which enhances inflammation and attracts immune cells to the site of infection.

Anaphylatoxins

Step 1 of Classical Pathway

Binding of C1 to antigen-antibody complexes.

Step 2 of Classical Pathway

C1 activates C2 and C4, leading to the formation of C3 Convertase.

C3 Convertase formation in Classical Pathway

The C4b2a complex that cleaves C3 into C3a and C3b.

Step 3 of Classical Pathway

C3b binds to the surface of the pathogen, marking it for opsonization.

Step 4 of Classical Pathway

C3b combines with C3 Convertase to form C5 Convertase.

Step 1 of Alternative Pathway

Spontaneous hydrolysis of C3 leads to C3b generation.

Step 2 of Alternative Pathway

C3b binds to a microbial surface and interacts with Factor B.

Formation of C3 Convertase in Alternative Pathway

The C3bB complex, stabilized by Factor D.

Step 3 of Alternative Pathway

C3 Convertase cleaves more C3, amplifying the response.

Final step in both pathways

Formation of the Membrane Attack Complex (MAC) leading to cell lysis.