Complement Pathways and Factor I Deficiency

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Questions and Answers

Describe a factor I deficiency.

Deficiency of factor I allows extended C3 convertase activity and for more production of C3 convertase of the alternative and classical pathways. Ultimately, this leads to depletion of C3, preventing activation of the complement cascades when they are really needed. Additionally, factor I deficiency prevents the formation of an important opsonin of complement, referred to as iC3b.

The classical pathway in the complement cascade is activated via what?

Antigens and antibodies coming into contact.

The lectin pathway in the complement cascade is activated by what?

Lectin binding to pathogen surfaces.

The alternative pathway in the complement cascade is activated by what?

Pathogen surfaces. Signup and view all the answers

What are the three functions of the complement cascade, irrespective of how the cascade is activated?

<ol> <li>Opsonization of pathogens.</li> <li>Recruitment of inflammatory and innate cells (primarily phagocytes).</li> <li>Direct killing of pathogens.</li> </ol> Signup and view all the answers

Which two complement pathways are purely innate?

The alternative and lectin pathways. Signup and view all the answers

Which complement pathway is considered to be an acquired immune response?

The classical pathway. Signup and view all the answers

In what order do the complement pathways act? (consider innate vs. acquired)

<ol> <li>Alternative pathway.</li> <li>Lectin pathway.</li> <li>Classical pathway (both innate and acquired).</li> </ol> Signup and view all the answers

What protein is involved when the classical pathway is activated in an innate capacity?

C-reactive protein. Signup and view all the answers

What are the two complement cascade products?

C3 is cleaved to C3a and C3b. Signup and view all the answers

Why is C3b the most important product of the complement cascade?

It is the primary opsonin created by these pathways. Signup and view all the answers

What are the three end products/results of the complement cascade?

<ol> <li>Recruitment of inflammatory mediator cells (anaphylatoxins).</li> <li>Opsonization of the pathogen by depositing C3b on its surface.</li> <li>Perforation of pathogen cell membranes (membrane attack complex).</li> </ol> Signup and view all the answers

What is the purpose of anaphylatoxins?

They are inflammatory mediators that activate vascular endothelium and recruit phagocytes to the inflammatory site. Signup and view all the answers

What is the purpose of opsonins?

They are easily recognized by phagocytes, encouraging them to engulf and destroy the pathogens. Signup and view all the answers

What is the purpose of the membrane attack complex (MAC)?

It causes the direct killing of the pathogen by disruption of its outer envelope, forming membrane pores. Signup and view all the answers

How are complement cascade opsonization different than antibody-mediated opsonization?

Complement opsonization is permanent as the complement proteins are covalently bound to the surface of the pathogen. Signup and view all the answers

What are the important things to know about the complement components?

<ol> <li>They are produced constitutively in the liver.</li> <li>They are secreted in their inactive zymogen form.</li> <li>They are always available in the circulation and in extravascular fluids throughout the body.</li> <li>Overactivation can lead to depletion of complement proteins because they are produced at steady state levels.</li> <li>MBL is the only one not expressed at a steady state.</li> </ol> Signup and view all the answers

What complement protein binds to antigen:antibody complexes and pathogen surfaces?

C1q. Signup and view all the answers

What complement protein binds to mannose on bacteria?

MBL. Signup and view all the answers

What complement proteins are activating enzymes?

<ol> <li>C1r, 2. C1s, 3. C2a, 4. Bb, 5. D, 6. MASP-2</li> </ol> Signup and view all the answers

What complement proteins are membrane-binding proteins and opsonins?

<ol> <li>C4b, 2. C3b.</li> </ol> Signup and view all the answers

What complement proteins are peptide mediators of inflammation?

<ol> <li>C5a, 2. C3a, 3. C4a.</li> </ol> Signup and view all the answers

What complement proteins are membrane attack proteins?

<ol> <li>C5b, 2. C6, 3. C7, 4. C8, 5. C9.</li> </ol> Signup and view all the answers

C3b is also a component of what other important cascade product?

It is a component of the C5 convertase enzyme that is required for activation of the membrane attack complex. Signup and view all the answers

How many versions of the C3 convertase enzyme are there?

Two: 1. C3b,Bb, 2. C4b,C2a. Signup and view all the answers

Study Notes

Factor I Deficiency

Factor I deficiency leads to prolonged activity of C3 convertase, enhancing C3 production.
Causes C3 depletion, hindering complement activation when necessary.
Lack of factor I prevents synthesis of iC3b, a vital opsonin.

Activation of Complement Pathways

Classical Pathway: Activated by the interaction of antigens with antibodies.
Lectin Pathway: Triggered when lectins bind to pathogen surfaces.
Alternative Pathway: Initiated by the presence of pathogen surfaces.

Functions of the Complement Cascade

Opsonization increases pathogen uptake and destruction by phagocytes.
Recruitment of inflammatory and innate cells, especially phagocytes.
Direct killing of pathogens.

Complement Pathway Classification

Innate Pathways: Alternative and lectin pathways are purely innate.
Acquired Pathway: The classical pathway is linked to the acquired immune response.
Pathways typically act in the following order: Alternative, Lectin, then Classical.

Key Proteins and Their Roles

C-reactive protein: Involved in classical pathway activation in an innate manner.
C3: Cleaved into C3a (anaphylatoxin) and C3b (opsonin).
C3b: Most significant product, serving as the primary opsonin.

End Products of the Complement Cascade

Recruitment of inflammatory mediator cells like anaphylatoxins.
Opsonization of pathogens through C3b deposition.
Formation of membrane attack complex (MAC) resulting in pathogen cell membrane perforation.

Functions of Complement Components

Anaphylatoxins: Activate endothelium and recruit phagocytes; enhance vascular permeability.
Opsonins: Facilitate phagocyte recognition and destruction of pathogens.
MAC: Directly kills pathogens by creating membrane pores.

Opsonization Comparisons

Complement opsonization differs from antibody-mediated opsonization as it permanently binds proteins to pathogen surfaces.

Complement Component Characteristics

Constitutively produced in the liver; secreted in inactive zymogen form.
Available in circulation and extravascular fluids; vulnerable to overactivation leading to depletion.
Mannose-binding lectin (MBL) is not produced at a steady state.

Specific Complement Proteins Functions

C1q: Binds to antigen-antibody complexes and pathogen surfaces.
MBL: Binds to mannose on bacteria.
Activating Enzymes: C1r, C1s, C2a, Bb, D, MASP-2.
Binding Proteins and Opsonins: C4b, C3b.
Inflammatory Peptide Mediators: C5a, C3a, C4a.
Membrane Attack Proteins: C5b, C6, C7, C8, C9.

C3 Convertase

C3b is integral to C5 convertase, essential for MAC activation.
There are two forms of C3 convertase: C3bBb and C4bC2a.

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Description

This quiz covers the intricacies of Factor I deficiency and its impact on the complement system. It explores the activation of different complement pathways and their functional roles in the immune response. Understand the mechanisms behind opsonization, phagocytosis, and the interaction of innate and acquired immune responses.