complement

Classical pathway

Initiated by antibody bound to antigen.

C3 convertase of classical pathway

C4b2a formed after C1 cleaves C4 and C2.

C3 convertase of alternative pathway

C3wBb formed when C3w binds factor B.

Lectin pathway

Initiated by mannose-binding lectin (MBL) binding carbohydrates.

Role of C1q

Binds to antibody after it has bound an antigen.

Functions of complement

Increases phagocytosis, enhances chemotaxis, and creates membrane attack complex.

Opsonins

C3b, C4b, iC3b increase phagocytosis and bind cellular receptors.

Anaphylatoxins

C5a, C3a, C4a cause histamine release, leading to inflammation.

Membrane Attack Complex (MAC)

C5-9 complex that forms pores in cell membranes.

CH50 assay

Measures complement function via the classical pathway, using sheep RBC lysis.

AH50 assay

Measures complement function via the alternative pathway, using rabbit RBC.

Components required for CH50

C1, C2, C4, C1INH are needed.

Components required for AH50

Factor B, Factor D, properdin, and Factor H/I.

C3 convertase

Enzyme complex responsible for cleaving C3 into C3a and C3b.

C1 inhibitor (C1INH)

Inactivates C1, regulating both classical and lectin pathways.

Deficiency in C1, C4, and C2

Increases risk of autoimmune connective tissue diseases and recurrent infections.

Deficiency in C3

Affects all pathways, leading to decreased phagocytosis and immune clearance.

DAF (Decay Accelerating Factor)

Regulates complement activation on cell surfaces to prevent bystander lysis.

Properdin

Stabilizes the C3wBb complex in the alternative pathway.

C5 convertase

Formed by C3 convertase complexed with C3b.

Complement receptor 1 (CR1)

Binds to C3b coated immune complexes for clearance in liver/spleen.

C3a

Small peptide that acts as an anaphylatoxin and is released during complement activation.

C5a

Powerful chemoattractant that promotes inflammatory response.

MBL-associated serine protease-2 (MASP-2)

Cleaves C2 and C4 in the lectin pathway.

Factor D

Splits factor B into Ba and Bb in the alternative pathway.

What is the classical pathway in the complement system?

The classical pathway is a part of the immune system that is activated by antibodies bound to pathogens, leading to the formation of a complement complex enhancing immune responses.

What triggers the alternative pathway in the complement system?

The alternative pathway is activated spontaneously on pathogen surfaces without the need for antibodies, providing a rapid immune response.

What are the components involved in the classical pathway?

Key components include C1, C2, C3, C4, C5, C6, C7, C8, and C9.

What are the components involved in the alternative pathway?

Key components include C3, factor B, factor D, and properdin.

What is a deficiency in the classical pathway associated with?

Deficiency in the classical pathway is associated with an increased risk of infections and autoimmune disorders.

What is a deficiency in the alternative pathway associated with?

Deficiency in the alternative pathway can lead to increased susceptibility to certain bacterial infections, particularly encapsulated organisms.

What is an opsonin?

An opsonin is a molecule that binds to pathogens and marks them for phagocytosis by immune cells, enhancing the immune response.

What are anaphylatoxins?

Anaphylatoxins are small peptides (C3a, C4a, and C5a) generated during complement activation that stimulate inflammation and an immune response.

What is the membrane attack complex (MAC)?

The membrane attack complex (MAC) is formed by complement proteins (C5b, C6, C7, C8, and C9) that create pores in the membranes of pathogens, leading to cell lysis.

What is chemotactic activity?

Chemotactic activity refers to the ability of certain molecules (such as C5a) to attract immune cells to the site of infection or inflammation.

What is the primary function of the classical pathway in the complement system?

The classical pathway helps clear pathogens by enhancing opsonization, inflammation, and promoting the formation of the membrane attack complex.

What does the alternative pathway contribute to in the immune response?

The alternative pathway provides rapid defense against invading pathogens and amplifies the complement response without the need for antibodies.

How does the lectin pathway complement the immune system?

The lectin pathway is triggered by the binding of lectins to specific carbohydrates on pathogens, aiding in opsonization and inflammation, similar to the classical pathway.

How do all three complement pathways work together?

All three pathways (classical, alternative, and lectin) converge to enhance the immune response, promoting opsonization, inflammation, and pathogen lysis.

What is the impact of complement pathways on inflammation?

Complement pathways enhance inflammation by generating anaphylatoxins that recruit and activate immune cells to the infection site.

What is the sequence of the classical pathway?

1. Antigen-antibody complex formation activates C1.
2. C1 cleaves C2 and C4, forming C3 convertase (C4b2a).
3. C3 convertase cleaves C3, leading to opsonization and MAC formation.

What is the sequence of the alternative pathway?

1. Spontaneous hydrolysis of C3 leads to the formation of C3w.

2. Factor B binds to C3w and is cleaved by factor D, forming C3 convertase (C3wBb).

3. C3 convertase cleaves more C3, amplifying the response and leading to MAC formation.

What is the sequence of the lectin pathway?

1. MBL (mannose-binding lectin) binds to specific carbohydrates on pathogens.
2. MBL-associated serine proteases (MASPs) are activated.
3. MASPs cleave C2 and C4 to form C3 convertase (C4b2a) that then cleaves C3, leading to opsonization and MAC formation.

How do the three pathways converge in the complement system?

All three pathways converge at the formation of C3 convertase, leading to the cleavage of C3, which is essential for opsonization, inflammation, and formation of the membrane attack complex (MAC).