Lecture 24 Complement System

Question 1

Innate immune system

Answer 1

The component of the immune system in animals that is genetically determined and is nonspecific as distinguished from the adaptive immune system.

Question 2

Elements of innate immune system

Answer 2

• Mucous secretions
• Complement proteins
• Certain White blood cells
• Especially neutrophils
• Macrophages
• Dendritic cells (medical dictionary)

Question 3

Adaptive Immune System

Answer 3

• The component of the vertebrate immune system involving lymphocytes (B cells and T cells) containing a small number genetically encoded proteins that combine to produce to an enormous variety of proteins capable of recognizing and deactivating specific antigens

Question 4

Complement Functions

Answer 4

1. Alters the membrane of pathogens and cellular debris

2. Enhance the inflammatory response

Question 5

Membrane Perturbation

Answer 5

• Alters membrane of pathogens and cellular debris
• Opsonization
• Opsonization leads to assembly of the membrane attack complex on pathogens and subsequent lysis

Question 6

Opsonization

Answer 6

coating promotes removal of particles via complement receptors on host cells

Question 7

Inflammatory response

Answer 7

-Release of anaphylatozins that promote cell activation (e.g. mast cell degranulation) migration
OR
- Migration to an inflammatory site (chemotaxis)

Question 8

What do mast cells produce?

Answer 8

Histamine

Question 9

What are the three types of complement system activation?

Answer 9

1. C3 turnover (Alternative Pathway)
2. Natural ABs (Classical pathway)
3. Lectins (Lectin Pathway)
   - Three mechanisms are independent of a prior adaptive immune response

Question 10

Complement activation

Answer 10

• innate immunity

- complement system becomes activated on a target such as apoptotic cells, tissue debris or pathogens

Question 11

C3 Turnover

Answer 11

• spontaneously activated

- Engages alternative pathway

Question 12

Binding of the target of naturally occurring antibodies engages what pathway?

Answer 12

Classical pathway

Question 13

Lectin pathway

Answer 13

binding of lectins to carbohydrates on the target

Question 14

Complement triggers the following immune functions

Answer 14

• Phagocytosis
• Inflammation
• Membrane attack

Question 15

Phagocytosis

Answer 15

• by opsonizing antigens

- C3b has most important opsonizing activity

Question 16

Opsonizing

Answer 16

coating invading organism with proteins that body will recognize and destroy

Question 17

Inflammation

Answer 17

• by chemotactically attracting marcrophages and neutrophils (anaphylatoxins C3a and C5a)

Question 18

Membrane attack

Answer 18

by rupturing cell wall of bacteria

Question 19

Inflammation

Answer 19

a local response to a cellular injury that is marked by capillary dilatation, leukocytic infiltration, redness, heat, and pain and that serves as a mechanism initiating the elimination of noxious agents and of damaged tissue (medical dictionary)

Question 20

Type 1 allergic reaction

Answer 20

• Wheal and flare
• Swelling is porduced by the release of serum into the tissues (wheal) and
• redness of skin resulting from the dilation of blood vessels (flare)

Question 21

What triggers the classic pathway?

Answer 21

Activation of C1 complex

Question 22

What does the mannose binding lectin pathway use instead of C1q?

Answer 22

• Opsonins
• Mannose binding lectin
• Ficolin

Question 23

How is the alternative pathway continuously activated at a low level?

Answer 23

As a result of spontaneous C3 hydrolysis due to the breakdown of the internal thioester bond
(the alternative pathway does not rely on pathogen-binding antibodies like the other pathways)

Question 24

Where do the Classical pathway, Lectin pathway, and alternative pathway converge?

Answer 24

C3 convertase

Question 25

How does the C1 complex proceed with opsonizing the pathogen surface?

Answer 25

1. C1 s cleaves C4 into C4 a and b and C2 into C2a and C2n 2. C4b and C2a bind forming the C4b2a complex 3. C4b2a is an active convertase of C3 4. C4b2a cleaves C3 into C3a and C3b (can cleaves 1000s of C3 molecules) 5. C3b binds and coats bacterial surface

Question 26

What is C3a's role in the complement system?

Answer 26

- it recruits phagocytes

Question 27

What are the two methods that C3b can be attack the bacteria after its thioester bond is exposed?

Answer 27

- Attack by H20 (soluble) | - Attack by R-HO or R-NH2

Question 28

What does the mannose binding lectin form a complex with?

Answer 28

Serine proteases

Question 29

Ficolins

Answer 29

- have a different binding domain than the Mannose binding lectin

Question 30

What complex does the mannose binding lectin pathway form to convert C3 to C3b and a?

Answer 30

C4b2a

Question 31

Where does the alternative start?

Answer 31

Once C3b is already bound to pathogen surface

Question 32

What are the steps of the alternative pathway?

Answer 32

1. C3b bound to surface (from classical or LBP) 2. C3b binds factor B 3. Factor B is cleaved by factor D 4. C3bBb complex is formed and is the C3 convertase

Question 33

`What pathway provides the C5 convertase?

Answer 33

Alternative

Question 34

How is the C3b2 formed?

Answer 34

another 3b molecule binds to it after being cleaved.

Question 35

What are the steps of the mac attack?

Answer 35

1. C5b binds to C6 and C7 2. C5b67 complex binds to membrane 3. C8 binds to complex and inserts into membrane 4. C9 molecules bind to the complex and polymerize 5. 10-16 molecules of c9 bind to form a pore in the membrane

Question 36

How do phagocytic cells bind to pathogen?

Answer 36

They have receptors that recognize the opsonization of C3b

Question 37

What needs to be present to internalize the bacterial cell?

Answer 37

C5A

Question 38

What does C5A do?

Answer 38

Activates macrophages to phagocytose/internalize

Question 39

Where are the factors that regulate the complement system?

Answer 39

The cell membrane of normal cells | -The factors prevent mac attacks

Question 40

How is the complement system regulated?

Answer 40

- Complement activation is regulated by a series of proteins that serve to protect host cells form accidental damage

Question 41

DAF Decay Accelerating factor

Answer 41

- Blocks the association of factor B with C3b | - Accelerates the dissociation of Bb from C3b in C3 convertase which stops the production of additional C3b

Question 42

MCP

Answer 42

dissociates C3 convertases at human cell surfaces and makes them susceptible to cleavage by factor I

Question 43

Hereditary angiodema

Answer 43

spontaneous random huge swelling

Question 44

What does MCP do?

Answer 44

Binds to C3b allowing factor I to cleave it.

Question 45

C3a, C5a

Answer 45

- Peptide mediators of inflammation | - Phagocyte recruitment

Question 46

C3b

Answer 46

- Binds to complement receptors on phagocytes - Opsonization of pathogens - Removal of immune complexes

Question 47

Terminal complement components | C5b, C6, C7, C8, C9

Answer 47

- membrane-attack complex | - Lysis of certain pathogens and cells

Question 48

Eculizumab

Answer 48

- inhibits C5 convertase | - Tested for HUS and paroxysmal nocturnal haemoglobinuria