The Complement System

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Questions and Answers

What is the complement system?

It’s a system of proteins that’s activated by the presence of pathogens. It’s made up of a large system of different plasma proteins that interact with one another

Most of the protein components are enzymes that become active ONLY after __.

Most of the protein components are inert enzymes that become active ONLY after cleavage

Which of the following is considered an adaptive pathway in the complement system?

Lectin

Classical (correct)

Alternative

More than one above

The classical pathway is activated by _______ bound to foreign antigens

The classical pathway is activated by antibodies bound to foreign antigens. Signup and view all the answers

What role does it play in immunity?

It generates biological active molecules important for full inflammatory response Signup and view all the answers

Each complement system pathway depends on different types of _______ for their initiation

Each complement system pathway depends on different types of molecules for their initiation Signup and view all the answers

All three pathways converge to generate the same set of _ complement components; which is ___

All three pathways converge to generate the same set of effector complement components; which is C3 convertase Signup and view all the answers

How do complement components contribute to the recruitment of immune cells?

By acting as chemoattractants for phagocytic cells Signup and view all the answers

What is the primary function of the activated complement proteins during opsonization?

To bind covalently to pathogens and target them for phagocytosis Signup and view all the answers

Which outcome is NOT associated with the activation of the complement system?

Immediate neutralization of toxins produced by pathogens Signup and view all the answers

In what way does the complement system enhance the adaptive immune response?

By opsonizing microbes for easier uptake by antigen-presenting cells Signup and view all the answers

What mechanism does the complement system use to kill microbes?

Pore formation in the microbial membrane leading to lysis Signup and view all the answers

The order of discovery of the nomenclature of complement components is ..

C1, C4, C2, C3, C5, C6, C7, C8, C9 Signup and view all the answers

Which of the following correctly describes a unique aspect of the nomenclature of complement components in the alternative pathway, as opposed to the classical pathway?

Complement components in the alternative pathway are designated by letters (e.g., Factor B and Factor D), while those in the classical pathway are numbered (e.g., C1, C4). Signup and view all the answers

The products of complement cleavage are designated by addition of a lower case letter. The smaller cleavage fragment is designated “b” and the larger cleavage fragment is designated “a”

False Signup and view all the answers

In the complement system, most cleavage products follow the convention where the larger fragment is labeled "b" and the smaller fragment is labeled "a." Which of the following describes the exception seen with C2 cleavage?

C2 is the only component where the smaller fragment is labeled "b" and the larger fragment is labeled "a." Signup and view all the answers

Which of the following proteins is responsible for initiating the classical pathway of complement activation?

C1 Signup and view all the answers

C1 can bind to the surface of pathogens in three different ways. Which of the following is NOT one of those mechanisms?

Binding to mannose residues on pathogen surface Signup and view all the answers

Out of the three ways C1 can bind to the surface of pathogens, which one is the most effective initiation? (Was in red)

Binds to antigen-antibody complexes on pathogen surface Signup and view all the answers

The lectin pathway of complement activation is initiated when

Mannose Binding lectin (MBL) or ficolins bind to specific carbohydrate structures, like mannose or N-acetylglucosamine, on the surface of microbes Signup and view all the answers

The alternative pathway of complement activation is initiated when

Spontaneous hydrolysis of C3 produces derived plasma C3b, which then binds to microbial surfaces Signup and view all the answers

The carbohydrate-binding proteins of the lectin pathway include ….

They include Mannose binding lectin and ficolins Signup and view all the answers

In each pathway, sequential reactions lead to generation of a protein complex called ____

C3 convertase Signup and view all the answers

In the complement cascade, what’s the primary function of C3b, and how does C3a contribute to the immune response, respectively?

C3b acts as an opsonin, tagging pathogens for destruction, while C3a serves as a mediator of inflammation by promoting immune cell recruitment. Signup and view all the answers

C3a acts as an opsonin, tagging pathogens for destruction, while C3b serves as a mediator of inflammation by promoting immune cell recruitment

False Signup and view all the answers

In the classical complement pathway, which immunoglobulins are the most potent activators, and how do they initiate the cascade?

IgM and IgG activate the classical pathway by binding C1q after they attach to antigens on pathogen surfaces Signup and view all the answers

The backbone of C1 is made up of __

C1q Signup and view all the answers

How is C1 activated in the classical pathway of the complement system?

It is activated when two globular heads of C1q bind two adjacent Fc regions of the antibodies bound to an antigen Signup and view all the answers

Describe events of the classical pathway cascade starting at after C1 activation

After C1 is activated, C1r cleaves itself, then cleaves adjacent C1s molecules, which activates protease activity of C1s. C1s cleaves C4 to C4a and C4b. C4b then covalently attaches to microbe/Ab-Ag complex. Then C1s cleaves C2 to C2b and C2a (large). C2a then binds to C4b forming the complex C4b2a on the surface of the microbe. This C4b2a is the classical pathways C3 convertase. C3 convertase cleaves C3 into C3a and C3b, then C3b attaches to the microbes. It’s now tagged for destruction by phagocytes micros Signup and view all the answers

Classical pathway: After C3b attaches to the surface to the pathogen (opsonization), what does C3b form a complex with?

It forms a complex with C3 convertase to form C5 convertase Signup and view all the answers

The lectin pathway is an independent innate immune response

True Signup and view all the answers

MBL is a tetrametric member of C-type lectin family, but doesn’t have structural similarities with C1q

False Signup and view all the answers

In the lectin pathway of complement activation, what does MBL recognize and bind to on the surface of pathogens?

Mannose, fructose, and N-acetylglucosamine residues Signup and view all the answers

In the lectin pathway of complement activation, what happens to Mannose-Binding Lectin (MBL) after it binds to a microbial cell wall?

MBL undergoes a conformational change, which activates MBL-associated serine proteases (MASPs) that cleave C4 and C2 Signup and view all the answers

Which statement best describes the role of C5b in the complement cascade?

It initiates the assemble y of the Membrane attack complex Signup and view all the answers

C3 is the most abundant complement protein and a key player in all pathways

True Signup and view all the answers

What complex functions as the alternative C3 convertase in the alternative complement pathway?

C3bBb Signup and view all the answers

What does the alternative complement pathway utilize to initiate the cascade?

Spontaneous cleavage of C3 Signup and view all the answers

In the alternative pathway, spontaneous cleavage of C3 results in which of the following events?

C3b binds to microbial surfaces and forms a complex with Factor B Signup and view all the answers

In the alternative pathway of complement activation, how is C3 convertase (C3bBb) stabilized on the microbial surface?

By Properdin Signup and view all the answers

The C5 convertase generated by all complement pathways initiate the formation of what?

It initiates the formation of the Membrane Attack Complex Signup and view all the answers

How do the C5 convertases from the classical, lectin and alternative pathway contribute to the initiation of the MAC formation?

All C5 convertases cleave C5 into C5b, which initiates the assembly of the MAC by binding to the target membrane Signup and view all the answers

How do complement control proteins help regulate complement activation?

By inhibiting the protease activities of complement components to prevent excessive activation Signup and view all the answers

Which complement pathway is regulated by Factor H, Factor I and Decay-Accelerating Factor (CD55)?

Alternative pathway Signup and view all the answers

How do Factor H and Factor I regulate the alternative pathway compared to CD55?

Factor H and Factor I bind to C3b, promoting its degradation and preventing further complement activation, while CD55 accelerates the decay of the C3 convertase (C3bBb) directly. Signup and view all the answers

How does Decay Accelerating Factor (CD55) regulate the alternative complement pathway?

CD55 accelerates the decay of C3 convertase (C3bBb), thereby preventing prolonged activation of the alternative pathway. Signup and view all the answers

Which of the following complement control protein acts on both the classical and lectin pathway?

C1 inhibitor Signup and view all the answers

How does the complement control protein C1 inhibitor regulate both the classical and lectin pathways of complement activation?

By inhibiting the activity of C1r and C1s in the classical pathway, and MASPs (MBL-associated serine proteases) in the lectin pathway. Signup and view all the answers

Why do C3 deficient dogs develop renal failure later in life?

C3 deficient dogs develop renal failure due to the complement system being unable to clear immune complexes effectively. Over time, the inability of C3b to facilitate the dissociation and clearance of immune complexes leads to their deposition in the kidneys. Signup and view all the answers

Study Notes

Complement System Protection Mechanisms

Complement proteins act as chemoattractants, drawing phagocytic cells to sites of activation, enhancing immune response.
Activated complement proteins bind covalently to pathogens, a process known as opsonization, marking them for phagocytosis.
Final complement activation components create pores in microbial membranes, leading to microbial cell lysis and death.

Role in Adaptive Immunity

Complement system supports adaptive immunity by enhancing the uptake of pathogens by antigen-presenting cells, such as dendritic cells.
B cells possess receptors for specific complement proteins, improving their response to microbes that have been opsonized with complement components.

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The Complement System

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Podcast

Questions and Answers

What is the complement system?

Most of the protein components are ____ enzymes that become active ONLY after ______.

Which of the following is considered an adaptive pathway in the complement system?

The classical pathway is activated by _______ bound to foreign antigens

What role does it play in immunity?

Each complement system pathway depends on different types of _______ for their initiation

All three pathways converge to generate the same set of _____ complement components; which is _______

How do complement components contribute to the recruitment of immune cells?

What is the primary function of the activated complement proteins during opsonization?

Which outcome is NOT associated with the activation of the complement system?

In what way does the complement system enhance the adaptive immune response?

What mechanism does the complement system use to kill microbes?

The order of discovery of the nomenclature of complement components is ..

Which of the following correctly describes a unique aspect of the nomenclature of complement components in the alternative pathway, as opposed to the classical pathway?

The products of complement cleavage are designated by addition of a lower case letter. The smaller cleavage fragment is designated “b” and the larger cleavage fragment is designated “a”

In the complement system, most cleavage products follow the convention where the larger fragment is labeled "b" and the smaller fragment is labeled "a." Which of the following describes the exception seen with C2 cleavage?

Which of the following proteins is responsible for initiating the classical pathway of complement activation?

C1 can bind to the surface of pathogens in three different ways. Which of the following is NOT one of those mechanisms?

Out of the three ways C1 can bind to the surface of pathogens, which one is the most effective initiation? (Was in red)

The lectin pathway of complement activation is initiated when

The alternative pathway of complement activation is initiated when

The carbohydrate-binding proteins of the lectin pathway include ….

In each pathway, sequential reactions lead to generation of a protein complex called ____

In the complement cascade, what’s the primary function of C3b, and how does C3a contribute to the immune response, respectively?

C3a acts as an opsonin, tagging pathogens for destruction, while C3b serves as a mediator of inflammation by promoting immune cell recruitment

In the classical complement pathway, which immunoglobulins are the most potent activators, and how do they initiate the cascade?

The backbone of C1 is made up of __

How is C1 activated in the classical pathway of the complement system?

Describe events of the classical pathway cascade starting at after C1 activation

Classical pathway: After C3b attaches to the surface to the pathogen (opsonization), what does C3b form a complex with?

The lectin pathway is an independent innate immune response

MBL is a tetrametric member of C-type lectin family, but doesn’t have structural similarities with C1q

In the lectin pathway of complement activation, what does MBL recognize and bind to on the surface of pathogens?

In the lectin pathway of complement activation, what happens to Mannose-Binding Lectin (MBL) after it binds to a microbial cell wall?

Which statement best describes the role of C5b in the complement cascade?

C3 is the most abundant complement protein and a key player in all pathways

What complex functions as the alternative C3 convertase in the alternative complement pathway?

What does the alternative complement pathway utilize to initiate the cascade?

In the alternative pathway, spontaneous cleavage of C3 results in which of the following events?

In the alternative pathway of complement activation, how is C3 convertase (C3bBb) stabilized on the microbial surface?

The C5 convertase generated by all complement pathways initiate the formation of what?

How do the C5 convertases from the classical, lectin and alternative pathway contribute to the initiation of the MAC formation?

How do complement control proteins help regulate complement activation?

Which complement pathway is regulated by Factor H, Factor I and Decay-Accelerating Factor (CD55)?

How do Factor H and Factor I regulate the alternative pathway compared to CD55?

How does Decay Accelerating Factor (CD55) regulate the alternative complement pathway?

Which of the following complement control protein acts on both the classical and lectin pathway?

How does the complement control protein C1 inhibitor regulate both the classical and lectin pathways of complement activation?

Why do C3 deficient dogs develop renal failure later in life?

Study Notes

Complement System Protection Mechanisms

Role in Adaptive Immunity

Studying That Suits You

Description

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Most of the protein components are enzymes that become active ONLY after __.

All three pathways converge to generate the same set of _ complement components; which is ___