Immuno 2.2 Classical Complement Pathway

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Questions and Answers

What is the complement cascade?

Sequential activation of complement proteins that occurs after a specific trigger.

What are the three stages of the complement system?

Recognition or initiation (binding to pathogen) 2. Amplification, proenzyme -> enzyme 3. Membrane attack complex (MAC)/biological effector expression

What are the 4 goals of the complement pathway?

Recognize and bind to pathogenic surfaces 2. Promote inflammatory response 3. Opsonize pathogen 4. Induce cellular lysis

What are the three complement pathways?

<ol> <li>Classical 2. Alternative 3. Lectin</li> </ol> Signup and view all the answers

What is involved in classical initiation?

IgG (antibodies) or a CRP (C-reactive protein) bind to the surface of a pathogen. Signup and view all the answers

Define classical initiation with CRPs.

The antibody binds to a pathogen. C1 then binds to the antibody. Signup and view all the answers

Define classical amplification with CRPs. (C1-C2)

After C1 binds to the antibody, it cleaves C4 into C4a and C4b. C4b attaches to the surface of the antigen and cleaves C2 into C2b and C2a. C2a binds to C4b on the antigen surface to form C3 convertase. Signup and view all the answers

What is C4a?

A modest inflammatory mediator. Signup and view all the answers

What is C2b?

It leaves the complement system after it is cleaved from C2. Signup and view all the answers

What is C3 convertase in CRPs?

C4aC2b Signup and view all the answers

Define classical amplification with CRPs. (C3C-C5)

After C3 convertase is formed, it cleaves C3 into C3a and C3b. C3b combines with C4bC2a on the antigen surface to form C5 convertase. Signup and view all the answers

What is C3a?

A major inflammatory mediator that causes degranulation, WBC stimulation, attracts WBCs, and increases phagocytosis. Signup and view all the answers

What is C5 convertase in CRPs?

C4bC2aC3b Signup and view all the answers

Define classical amplification in CRPs. (C5C-C5)

C5 convertase cleaves C5 into C5a and C5b. C5b attaches to the pathogen surface. Signup and view all the answers

What is C5a?

A major inflammatory mediator. Signup and view all the answers

What is the MAC and how is it formed?

Membrane attack complex formed through a chain of recruitment. When C5b binds to the pathogen surface, it recruits C6, C7, C8, and C9 respectively. The addition of C9 forms the MAC. Signup and view all the answers

What does the MAC do?

The addition of multiple C9 molecules creates pores in the membrane of the pathogen, disrupting the concentration gradients between the intra and extracellular environments, causing the cell to explode. Signup and view all the answers

Summary of classical complement pathway.

Recognizes and binds to pathogens, promotes inflammatory response, opsonizes pathogen, induces cellular lysis, increases phagocytosis, clumps viruses together, breaks apart the virus envelope membranes. Signup and view all the answers

Study Notes

Complement Cascade

Involves the sequential activation of complement proteins triggered by specific stimuli.

Stages of the Complement System

Recognition/Initiation: Binding of complement proteins to pathogens.
Amplification: Conversion of proenzymes into active enzymes, creating a cascade effect.
Membrane Attack Complex (MAC): Formation of a structure that leads to cell lysis.

Goals of the Complement Pathway

Recognize and attach to pathogen surfaces.
Facilitate an inflammatory response.
Tag pathogens for opsonization, enhancing phagocytosis.
Trigger cellular lysis through the MAC.

Complement Pathways

Classical
Alternative
Lectin

Classical Pathway Initiation

Initiated by binding of IgG antibodies or C-reactive protein (CRP) to pathogens.

Classical Initiation with CRPs

Antibodies bind to pathogens, followed by C1 binding to the antibody.

Amplification Process with CRPs (C1-C2)

C1 cleavage activates C4, producing C4a and C4b.
C4b attaches to the pathogen and cleaves C2 into C2a and C2b.
C2a binds to C4b to form C3 convertase.

C4a and C2b

C4a is a modest inflammatory mediator.
C2b is released from the complement system after C2 cleavage.

C3 Convertase in CRPs

Formed as C4aC2b.

Further Amplification (C3C-C5)

C3 convertase cleaves C3 into C3a and C3b.
C3b combines with C4bC2a to form C5 convertase.

C3a and C5 Convertase

C3a is a significant inflammatory mediator, leading to WBC stimulation and increased phagocytosis.
C5 convertase is composed of C4bC2aC3b.

C5 Cleavage Process

C5 convertase cleaves C5 into C5a and C5b.
C5b anchors to the pathogen surface.

C5a

Acts as a major inflammatory mediator.

Membrane Attack Complex (MAC)

Formed through recruitment initiated by C5b, which recruits C6, C7, C8, and C9.
Multiple C9 molecules assemble to create pores in the pathogen membrane, leading to cell lysis.

Role of the MAC

Disrupts ion concentration gradients, resulting in pathogen cell destruction.

Summary of Classical Complement Pathway

Recognizes and attaches to pathogens, enhancing inflammation and opsonization.
Induces cellular lysis, increases phagocytosis, aggregates viruses, and disrupts virus envelopes.

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Test your knowledge on the classical complement pathway with this flashcard quiz. Learn about the complement cascade, its stages, and key functions in the immune response. Perfect for Immunology students studying module 2.2.