What is Complement?

·      Series of more than 30 soluble and cell bound proteins that interact to enhance host defense mechanisms against foreign agents

Part of both the innate and antibody-mediated acquired immune response

How is the classical pathway started?

activated when C1 binds to ag:ab complex (mostly ab bound to surface of pathogen)

·      the only antibodies capable of binding are two units of IgG or one IgM although IgM is more effective

How is alternative pathway acitvated

how is lectin pathway activated

activated when mannin-binding (MBL) binds to terminal mannose residues on surface of gram + and - bacteria, fungi, and yeast

o   Contain mannose in cell walls or outer covering. 

Name the first steps in classical pathway

·      The activated C1 then cleaves C2 into C2a and C2b and C4 into C4a and C4b

·      C2a and C4b combine to form a protease called C3 convertase, which cleaves C3 into C3a and C3b 

How are Lectin and classical pathway same? different?

the same: activation proceeds through the action of cleaving C4 and C2 to  form C4b2a ......produce activated complement proteins further down the cascade

Different:lectin pathway does not recognize antibody bound to its target. The lectin pathway starts with mannose binding lectin, (MBL)

What is C3 convertase called in classica, lectin, and alternative pathway?

Classical/lectin - C4b2a

Alternative- C3bBb

What does C3b do? C3a?

C3a- enhances inflammation and is chemoattractant for phagocytes

C3b- o   attaches to the surfaces of microorganisms. Phagocytes have a binding site for C3b

·      Microorganisms with C3b on their surface are more susceptible to phagocytosis (opsoninization) 

·      Adding properdin to C3 convertase, which cleaves C5 into C5a and C5b. 

What does c5a do? c5b?

·      C5a enhances inflammation and acts as a chemoattractant for phagocytes.

·      C5b reacts with other complement C6,C7,C8 and C9 to form a membrane attack complex

o   This structure forms a hole in the cell and causes cell to lyse 

How does C11NH regulate complement?

Classical- binds to C1r and C1s to dissociate from C1q

Alternative- inhibits function of C3bBb

Lectin- inhibits MASP1, and MASP2

Name the molecules distributed on cell surface that regulate the classical and lectin pathway C3 convertase (C4b2a)

o   C4 binding protein (C4BP)

o   Decay accelerating factor (DAF or CD55)

o   Complement receptor 1 (CD 35)

o   Membrane cofactor protein (MCP or CD 46) 

What does Factor 1 and Factor H do?

·      Factor 1: this cleaves C4b on the cell surface after C2 has been displaced

·      Factor H: competes with previously mentioned factor B for binding to C3. If it bonds to C3b the pathway stops.

·      Most important function of complement is the generation of opsonic fragments that are deposited on the surface of pathogens

*C3b and C4b are the major opsonins created

·      Anaphylatoxin: a molecule that induces potent inflammatory responses. The creation of these is the 2^nd most important function

o   C5 is the most potent followed by C3a, C4a is much less potent

What is the third major function in complement?

Lysis

·      The terminal steps in all three pathways are the formation of MAC ion the surface of a cells which results in lysis 

how are B-cells enhanced in responding to antigens?

o   C3dg binding to antigen and the b cell surface increase activation by 1000 fold compared to in the absence of C3dg, (a breakdown product of C3) 

What is used in the breaking of complex bonds that cause agglutination in the body?

 The depositing of C3b on large antigen antibody complexes interferes with the bonds that keep it together.

What can bind directly to and become activated by the surface of several viruses?

C1