Immunology: The Complement System

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Questions and Answers

What is the primary function of the complement system as described?

To inhibit pathogen entry

To induce apoptosis in infected cells

To support antibody binding

To activate the immune response (correct)

Which pathway is activated by the binding of C3b according to the given information?

Classical pathway (correct)

Lectin pathway

Allergic pathway

Alternative pathway

What components are activated by the classical complement pathway?

C3 and C5

C4 and C6

C2 and C4 (correct)

C2 and C3

What condition is associated with deficiencies in the complement system?

Autoimmunity Signup and view all the answers

Which protein complex is indicated to play a critical role in the complement activation process?

MASP Signup and view all the answers

What type of cellular interaction is primarily initiated by the opsonization process?

Phagocytosis Signup and view all the answers

Which pathway is considered unique for having antibody-dependent activation of complement?

Classical pathway Signup and view all the answers

What initiates the process of complement activation in the presence of an antigen-antibody complex?

C1q binding Signup and view all the answers

Which complement component is involved in the opsonization of pathogens?

C3b Signup and view all the answers

What is the spontaneous activation event mentioned in the context?

Initiation of the alternative pathway Signup and view all the answers

What role does Factor B play in the activation process?

It binds to C3b to start the activation. Signup and view all the answers

Which of the following proteins is known to block the C3 convertase?

Factor H Signup and view all the answers

What is the consequence of having a deficiency in Factor I?

Decreased blockage of C3 convertase. Signup and view all the answers

Which inhibitors work together to block the activation of the complement system?

MCP and Factor H Signup and view all the answers

In the process of complement activation, which statement is true about C5 convertase?

It activates C5 to form the membrane attack complex. Signup and view all the answers

How does Factor Cy influence the convertase activity?

It inhibits the formation of C3 convertase. Signup and view all the answers

Which function do CD55 and CD35 share in regard to the complement system?

They act as inhibitors preventing complement activation. Signup and view all the answers

What can be a potential outcome of activating Factor 1?

It leads to effective regulation of complement activity. Signup and view all the answers

Which component is necessary for the formation of the 23 convertase?

C3b Signup and view all the answers

What is a characteristic of the process involving C3i?

It requires Factor 1 for activation. Signup and view all the answers

Study Notes

The Complement System

Complement system is a part of the immune system that helps fight infections.
Classical pathway of complement activation involves antibodies binding to antigens.
This creates an antigen-antibody complex which activates C1q (a component of the complement system)
C1q activates C4 and C2 (other complement components)
C4b and C2a complex is formed. This complex activates C3 (another complement component)
C3b binds to the complex, creating C4b2a3b, also known as C5 convertase
C5 component is cleaved into C5a and C5b
C5a is an anaphylatoxin (a molecule that can cause release of histamine from cells, contributing to inflammation)
C5b initiates the formation of the membrane attack complex (MAC)
MAC forms a pore in the target cell, leading to cell lysis (cell death).

Alternate Pathway

Alternate pathway is another way the complement system is activated
This pathway starts directly with C3 binding to the pathogen surface
C3b is generated by the Alternate pathway
C3b interacts with factor B and factor D
This forms the C3 convertase ( C3bBb complex)
C3 convertase leads to the formation of C5 convertase & MAC formation
The Alternate pathway is important in innate immunity.

Lectin Pathway

Lectin pathway is triggered by the binding of mannose-binding lectin (MBL) to specific carbohydrates on the surface of microbes.
MBL binds to MASPs (MBL associated serine proteases)
MASPs are proteases (enzymes that break down proteins) which cleave C4 and then C2
C4b2a complex is generated and activates C3
C3b binds to the complex, creating C4b2a3b (C5 convertase)
C5 component is cleaved into C5a and C5b
C5a is an anaphylatoxin (a molecule that can cause release of histamine from cells, contributing to inflammation)
C5b initiates the formation of the membrane attack complex (MAC)
MAC forms a pore in the target cell, leading to cell lysis (cell death).

Complement Deficiencies

Complement deficiencies occur when one or more components of the complement system are missing or not working properly.
These deficiencies can increase the risk of infections
Examples include C3 deficiency, factor H deficiency
C3 deficiency: It is more common, can lead to frequent infections and can cause recurrent bacterial infections.
Factor H deficiency: Can lead to atypical hemolytic uremic syndrome (aHUS), an autoimmune disease where antibodies attack red blood cells which can lead to severe anemia and kidney failure.

Regulation of the Complement System

Complement system needs to be tightly regulated to prevent damage to host tissues
This is done by several regulatory proteins that inhibit the complement system's activity or prevent its activation when it’s not needed
Examples of regulatory proteins include:
- C1 inhibitor (C1INH)
- Factor H
- Factor I
- DAF (decay-accelerating factor)
- MCP (membrane cofactor protein)
- CR1 (complement receptor 1)### Complement System: Activation and Regulation
C3 Convertase activation requires Factor B binding to C3b and subsequent hydrolysis by Factor D.
C3 Convertase (C3bBb) can then further amplify the cascade by cleaving C3 into C3a and C3b, which then binds to more Factor B, continuing the cycle.
Regulation of the Complement System: There are several mechanisms to prevent uncontrolled complement activation.
- C1 Inhibitor (C1INH) specifically binds to and inactivates the activated C1 complex.
- Factor H and C4-binding protein (C4BP) are soluble regulators that promote C3b inactivation by Factor I, preventing the formation of new C3 convertase.
- Membrane Cofactor Protein (MCP), Decay-accelerating factor (DAF), and CD59 are complement regulatory proteins (CRPs) that are expressed on cell surfaces and serve to regulate complement activation, preventing excessive damage to host cells.

C3 Convertase Inhibition

C3 Convertase (C3bBb) can be blocked by different mechanisms:
- Factor I can directly cleave and inactive C3b.
- CRPs such as MCP, DAF, and CD59 can bind to C3bBb, making it susceptible to inactivation by Factor I.
- Properdin can help to stabilize C3bBb, promoting its activity.

C5 Convertase and MAC Formation

C5 Convertase is formed when C3bBb binds to C3b (C3bBbC3b).
C5 Convertase cleaves C5 into C5a and C5b.
C5b initiates the formation of the Membrane Attack Complex (MAC) by binding to C6 and C7, forming a complex that inserts into cell membranes.
C8 joins the complex, followed by C9, creating a pore in the cell membrane, leading to cell lysis.

Regulation of MAC Formation

CD59 acts as a potent inhibitor of the MAC formation, preventing the insertion of C9 into the cell membrane.
Vitronectin can also prevent the MAC formation by binding to C5b67 and preventing further assembly of the complex. This is important for regulating complement activation, preventing self-damage of host cells.

C3 Deficiency

A deficiency in C3 can manifest as recurrent bacterial infections due to the crucial role of C3 in the complement cascade.
A deficiency in C1INH is linked to Hereditary Angioedema (HAE), a condition characterized by recurrent edema attacks, most commonly affecting the face, extremities, and airway.

Important for the Exam

Remember the key mechanisms of activation and regulation of the complement system.
Understand the roles of C3 Convertase, C5 Convertase, and the MAC complex.
Be familiar with the major complement inhibitors and regulators, including C1INH, Factor H, MCP, DAF, and CD59.
Know the consequences of complement deficiencies such as C3 and C1INH deficiencies.

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Description

Test your knowledge on the complement system, a crucial part of the immune response. This quiz covers both the classical and alternate pathways of complement activation, including the roles of various components and mechanisms. Dive into how these pathways contribute to fighting infections and the formation of the membrane attack complex.