Chpt 13 Complement

Front 1

What is the complement system?

Back 1

The major effector of the humoral branch of the immune system.

The activity of blood serum that completes the action of antibody.

Front 2

4 functions of complement

Back 2

1. Lysis of cells, bacteria, viruses
2. Opsonization
3. Binding specific complement receptors to Trigger inflamm, regulation
4. immune complex clearance of

Front 3

is complement heat stabile or labile?

Back 3

labile; heating destroys its ability to lyse infected cells.

Front 4

3 activation pathways:

Back 4

1. Classical
2. Alternative
3. Lectin

Front 5

How is the classical pathway initiated?

Back 5

formation of Ag-Ab complex.
This induces a conformational change in the Fc region of the antibody to allow C1 to bind the complex (by antibody)

Front 6

Step 2 of classical pathway

Special requirement:

Back 6

C1 binds 2 Fc regions of antibody (that is complexed to antigen).

C1 must have 2 Fc regions accessible; IgM is much better at activating classical pathway than IgG

Front 7

Step 3 of classical pathway

Back 7

rapid hydrolysis of C3 into C3a and C3b.

initiates cascade that forms MAC

Front 8

what is the mechanism of complement?

Back 8

proteolysis

Front 9

What allows C3b to act as an opsonin?

Back 9

Internal thioester bond in C3 is activated when it's cleaved and it ends up on C3b so it has free sticky chemical group to bind to free OH or amine groups on cell membranes. (phagocytic cells)

Front 10

Function of:
C3a
C3b

Back 10

C3a --> anaphylatoxin; mediates inflammation

C3b --> opsonin for phagocytosis; coats immune complexes and particulate Ag.

Front 11

For which pathways is Ab necessary?
Which are components of innate immunity?

Back 11

ONLY Classical needs antibody.

Alternative and Lectin are innate.

Front 12

Initiation of Alternative pathway:

Back 12

Serum C3 just hydrolyzes very slowly into c3a/c3b. the sticky group on C3b then binds to groups on foreign molecules (bacteria, Ag).

Triggers a bunch of steps that results in MAC formation.

Front 13

Which antibody needs to be in higher concentration to activate complement?

Back 13

IgG much higher than IgM; need 2 binding sites for C1 to activate complement.

Front 14

what can activate the alternative pathway?

Back 14

pathogens, microbial particles, and even host self-cells that are recognized as non-self.

Front 15

role of complement in viral neutralization:

Back 15

C3b sticky ends bind to viruses in circulation; coats the surface and allows phagocytosis!

Front 16

what is lectin?

Back 16

an acute phase protein from inflammation. innate response produces this molecule to activate complement for lysis of bacteria.

Front 17

what are the two steps of the Lectin activation pathway?

Back 17

1. Lectin binds Mannose (carb) on bacterial surface.

2. Serine protease binds Lectin and activates cleavage of C2 and 4, and the complement cascade.

Front 18

What is the point of convergence of the three activation pathways?

Back 18

MAC formation.

Front 19

how does c3b mediate opsonization?

Back 19

Phagocytes have complement receptors. when complement proteins coat the surface of antigen, the proteins then bind receptors and activate the function.

Front 20

what molecule polymerizes to form MAC?

Back 20

C9

Front 21

How does MAC cause lysis of cells?

Back 21

By forming a pore in their membrane, allows diffusion of ions across membrane and disrupts osmotic stability -> causes lysis

Front 22

what are the 2 regulatory mechanisms of complement?

Back 22

1. Inactivate complement components. Proteins cleave very unstable, short-lived intermediates to stop cascade.

2. Inactivate anaphylatoxin

Front 23

What are the 6 consequences of complement activation?

Back 23

1. Lysis of cells, GNB, and envel. virus
2. particulate Ag opsonization
3. Inflammatory activation
4. local clearance of Ag-Ab complex.
5. Viral neutralization
6. Systemic clearing of Ag-Ab complex.

Front 24

How can innate immunity activate complement by all three pathways?

Back 24

Microorganisms can activate Altern/lectin by their surface ag.

Classical can be activated by common surface molecules on ubiquitous microorganisms.

Front 25

How can MAC lyse viruses?

Back 25

It can insert pores into the viral envelope because it is made of plasma membrane (from the host)

Front 26

What type of bacteria are more commonly lysed by MAC?

Back 26

Gram negative - the peptidoglycan of Gram positive evades MAC insertion.

Front 27

What is special about RBC lysis by MAC?

Back 27

only requires one molecule of MAC;

nucleated cell lysis requires multiple MACs.

Front 28

what are the two functions of C3a that mediate inflammation?

Back 28

1. cause degranulation

2. chemotactic

Front 29

How does c3a cause chemotaxis?

Back 29

binds molecules already at the inflammatory site, induces binding of other neutrophils/monocytes to bind epithelial cells, extravasate, and arrive at inflamm site.

Front 30

how does c3a mediate degranulation?

Back 30

mast cells/basophils have receptors for it; binding induces degranulation.

Front 31

How does C3A help C3B be a better opsonin?

Back 31

anaphylatoxins induce upregulated c3b receptors on macrophages and phagocytic cells.

Front 32

3 Methods of Complement neutralization of Viruses:

Back 32

1. simply the fact aggregates formed from c3b-coating reduces the # of viral particles.

2. Complement coating prevents virus from binding host cells/infecting them.
3. Opsonization allows phagocytosis of virus-c3b aggregates.

Front 33

Mac-lysis would cause spreading of Viral DNA; how is this prevented?

Back 33

Coating virus w/ complement proteins allows phagocytosis, packaging the degraded virus and preventing spread.

Front 34

2 ways to kill viruses with complement:

Back 34

1. Phagocytosis (via opsonization)
2. Enveloped viruses get MAC-lysed

Front 35

What is the result of insufficient levels of C1,2, or 4?

Back 35

Insufficient levels of C3; insufficient complement

Front 36

What role do RBCs play in immune complex-clearing?

Back 36

Have CR1-receptor; this binds C3b-coated immune complexes, carry to spleen/liver. Then, Complex is stripped and phagocytosed; RBCs return to circulation.

Front 37

Why do lupus patients have tissue damage?

Back 37

produce too much immune complex;
produce too little c3b;

complexes persist (RBC don't bind if there's no c3b on complex) and activate MAC lysis instead of phagocytosis in spleen/liver

Front 38

consequences of complement deficiency:

Back 38

-recurrent bacterial infections
-tissue damage due to persistent Ag-ab complexes