immuno lect 2 part 2

complement must be activated to be functional by what pathways

classical, lectin, alternative

What are the 3 main consequences of complement activation?

Inflammation and chemotaxis, opsonization, and direct lysis of microbes

Is complement innate or adaptive?

innate

How many complement proteins are there?

More than 30

Who produces complement?

Hepatocytes (mainly), monocytes/macrophages, and GI epithelial cells

Where is complement found?

Free in serum (about 10% of serum protein) and body fluids, on cell surfaces as receptors, and in neutrophil granules

What form are complement proteins in when healthy?

Inactive precursors (serine protease proenzymes)

How do complement proteins get activated?

They are cleaved by the protein immediately upstream. Each active protein then activates several downstream proteins

What is the key feature of the cascade?

Massive amplification.

How are complement proteins numbered?

By order of discovery, not by order in the cascade.

What does a lowercase letter (C3a, C3b) mean?

A cleavage product.

What does a name like C4b2a mean?

A complex, with components listed in the order they joined. C4b2a is C3 convertase.

What are letter-only components (B, D, H, P) called?

“Factors,” such as Factor H.

What activates the alternative pathway?

Complement binding directly to the pathogen surface (C3, factors B, D, P).

What activates the classical pathway?

Antibody bound to the pathogen (C1, C4, C2).

What activates the lectin pathway?

Mannose-binding lectin binding mannose on the pathogen wall (MASP-1, MASP-2, C4, C2).

What is the one goal of all 3 pathways?

Removal of the pathogen.

What 3 ways does complement remove pathogens?

It facilitates phagocytosis, kills directly, and promotes inflammation.

What counts as a “pathogen” for complement?

A microbe or a dead cell.

What key effector protein do all 3 pathways generate?

C3 convertase

Which fragments recruit inflammatory cells?

C3a and C5a

Which fragment opsonizes?

C3b.

What does direct killing?

The membrane attack complex (MAC), made of C5 to C9.

What does C3a do?

It contracts smooth muscle, increases vascular permeability, and degranulates mast cells and basophils

C3a is a potent

anaphylatoxin

What does C5a do?

It drives neutrophil chemotaxis, adhesion, activation, and degranulation

C5a triggers release of

prostaglandins and leukotrienes

What do prostaglandins cause?

Increased vascular permeability and vasoconstriction

How does C3b lead to phagocytosis?

C3b coats the bacterium, binds the complement receptor on a phagocyte, and the phagocyte engulfs it

How does the MAC form?

C5b, C6, C7, and C8 aggregate. This triggers C9 to polymerize into a pore

What does the MAC do?

It punches a hole in the pathogen membrane, causing lysis.

What are the 3 steps of complement activation? step 1

A pathway is activated (alternative, lectin, or classical)

What are the 3 steps of complement activation? step 2

C3 convertase is generated

What are the 3 steps of complement activation? step 3

The MAC (C5 to C9) and fragments C3a, C5a, and C3b are produced, all of which remove the pathogen

terminal complement complex job is the

lysis of a pathogen

Why does complement need tight control?

It is very potent and could damage host cells.

What does C1-inhibitor (C1-INH) do?

It inhibits activated C1 in the classical pathway

What does CD55 (decay accelerating factor) do?

It speeds degradation of complement on red cells, leukocytes, platelets, and endothelium, protecting them

What does Factor H do?

It has a similar function to CD55

What does CD59 (protectin) do?

It blocks assembly of the MAC.

What do complement receptors do in regulation?

They remove antigen-antibody-complement complexes, mainly through C3 receptors.