Classical & Lectin Pathways - Complement System

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Questions and Answers

How many proteins is the Complement System composed of?

30+ proteins

What are Proteases active only after cleavage usually by another specific protease?

Complement Proteins

What is the inactive form of a complement protein called?

Proenzymes or Zymogens

Where is the complement system produced?

Liver Signup and view all the answers

When is the complement system activated?

When they come across a pathogen Signup and view all the answers

Where is the Complement system activated?

On the surface of pathogen/bacteria Signup and view all the answers

Which two antibodies are capable of initiating complement activation?

IgM & IgG Signup and view all the answers

What are the effector functions of the Complement System?

Humoral Immunity & Inflammation Signup and view all the answers

What are the three functions of the Complement System?

Opsonization, MAC, Inflammation Signup and view all the answers

How do the Complement System proteins get activated?

By interacting with each other - Inducing a cascade of activation Signup and view all the answers

What is the innate immune system composed of?

Physical, Chemical, and Biological barriers Signup and view all the answers

How many Complement pathways are there?

Three - Classical, Alternative, and Lectin Signup and view all the answers

What do the complement pathways have in common?

They all help activate C3 to C3 Convertase Signup and view all the answers

What happens when the complement protein coats the outer surface of a pathogen?

Opsonization Signup and view all the answers

What is caused by a group of complement proteins forming a hole in a pathogen?

Membrane Attack Complex (MAC) Signup and view all the answers

What is the first complement pathway to be discovered?

Classical Pathway Signup and view all the answers

How is the Classical pathway triggered?

Formation of Antigen:Antibody complex Signup and view all the answers

What is the first step of the Classical pathway?

Antibody binds to Antigen on the surface of a pathogen Signup and view all the answers

What happens in the 2nd step of the Classical pathway?

C1 Complex binds to Fc regions on Antibodies - activating the C1r & C1s proteases Signup and view all the answers

What involves C4 cleavage and which enzymes are responsible?

C4 Cleavage by C1r(2)-C1s(2) enzyme Signup and view all the answers

What kind of bond is formed when C4b covalently binds to an antigen?

Covalently binds to cell surface Signup and view all the answers

What happens when C2 comes in contact with the C1 complement complex?

C2 cleaved into C2a & C2b Signup and view all the answers

Which proenzyme binds to C4b?

C2 proenzyme Signup and view all the answers

What activates and cleaves C2 proenzyme attached to C4b?

C1s Signup and view all the answers

What happens to C2a and C2b after cleavage?

C2a binds to C4b forming C3 Convertase, C2b is released Signup and view all the answers

What is C1 Complement Complex composed of?

C1q - C1r - C1s Signup and view all the answers

What does C1q bind to?

Antigen:Antibody complexes & pathogens Signup and view all the answers

What does C1 Complement Complex binding to Antibody:Antigen complex activate?

C1r & C1s proteases Signup and view all the answers

Which component cleaves and activates in the Classical Pathway?

C1s protease - Cleaves C4 Signup and view all the answers

What is the product of cleaving C4?

C4a and C4b Signup and view all the answers

What does C1s cleave C2 into?

C2a (binds to C4b) and C2b (released) Signup and view all the answers

What does C4bC2a form?

Classical Pathway C3 Convertase Signup and view all the answers

What does C3 Convertase do?

Binds and proteolytically cleaves C3 into C3b & C3a Signup and view all the answers

What does C3a trigger?

Inflammation by binding to leukocyte receptors Signup and view all the answers

What happens to C3b?

Inactivated by Hydrolysis; forms covalent bond with cell surfaces; binds to Antibody Complex Signup and view all the answers

What is C5 Convertase?

When C3b binds to C4b2a (C3 convertase) Signup and view all the answers

What does C4b3b2a represent?

C3/C5 Convertase Signup and view all the answers

What does C5 Convertase do?

Cleaves both C3 and C5 to form C5a & C5b Signup and view all the answers

Study Notes

Complement System Overview

Composed of over 30 proteins that circulate in an inactive form to prevent self-attack.
Activation occurs when proteins encounter pathogens or antibody-bound antigens on cell surfaces.

Proteins and Activation

Inactive forms of complement proteins are referred to as proenzymes or zymogens.
Active proteases induce a cascade of interactions to trigger further complement activation.
Notable antibodies, IgM and IgG, initiate complement activation upon binding to antigens.

Key Processes and Functions

Major effector functions include opsonization, formation of the Membrane Attack Complex (MAC), and triggering inflammation.
Opsonization marks pathogens for easier phagocytosis by immune cells.
MAC creates pores in pathogen membranes, leading to cell lysis.

Complement Pathways

There are three complement pathways: classical, alternative, and lectin, all designed to activate C3 to C3 Convertase.
The classical pathway is the first discovered and gets triggered by antigen-antibody complex formation.

Classical Pathway Steps

Antibodies bind to antigens on pathogens, leading to the binding of the C1 complex.
C1 complex cleaves C4 into C4a and C4b, where C4b covalently bonds to the pathogen surface.
C2, upon contact with C1 complex, is cleaved into C2a and C2b; C2a binds to C4b to form C3 Convertase (C4b2a).

Cleavage and Product Formation

C3 Convertase cleaves C3 into C3a and C3b, perpetuating the complement response.
C3a promotes inflammation, while C3b can opsonize pathogens or bind to antibody complexes.

C5 Convertase

C5 Convertase is formed when C3b binds to C4b2a, and it cleaves C5 into C5a and C5b.
Cleavage products C4a, C4b, C2a, and C2b play roles in further complement activation and regulation.

Components of C1 Complex

C1 complement complex includes C1q (pathogen sensor), C1r, and C1s.
C1q binds to antibody-antigen complexes, activating downstream proteases C1r and C1s for further complement activation.

Important Binding Characteristics

C4b forms covalent bonds with pathogen surfaces, crucial for opsonization and complement activity.
The sequential nature of complement activation ensures a rapid immune response against pathogens.

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Test your knowledge on the classical and lectin pathways of the complement system with these flashcards. Gain a deeper understanding of the proteins involved, their activation, and the overall function of this important immune system component.