Complement

Question 1

part of which immunity

Answer 1

humoral- soluble

Question 2

consists of how many serum and membrane proteins

Answer 2

30

Question 3

how does complement mediate the immune reaction

Answer 3

• triggering inflammation
• attraction of phagocytes to sites of infection
• degradation of membrane or virus envelope
• stimulation of antibody production

Question 4

activation of complement

Answer 4

the active components of complement ar egernated from inactive precursors by a cascade of proteolytic reactions

Question 5

how many pathways trigger activation of complement

Answer 5

3

Question 6

name the three complement pathways

Answer 6

1) the lectin pathway
2) the classical pathway
3) the alternative pathway

Question 7

the lectin pathways

Answer 7

recognition of carbohydrate molecules e.g. by collectins such as mannose-binding lectin

Question 8

the classical pathway

Answer 8

pathway which was first described

- antibody binding to antigen in immune complexes

Question 9

the alternative pathway

Answer 9

directly activated by microbial cell surfaces

Question 10

all initiations of complement pathways start

Answer 10

differently but end in the same way

Question 11

complement reactions

Answer 11

can be divided into early events, in which components are not the same for the three pathways and the late event, in which they are identical

Question 12

early events

Answer 12

1) function of the early events is to generate to functionally equivalent forms of a proteases, known as C3 convertase
2) C3 convertase then initiates the late events to produce the effector components of complement
3) C3 convertase covalently attaches to the cell surfave at which the complement activation was initiated
4) cleavage of complement component C3 leads to effector activation- effects of complement activation aere confined to the infectious organism that triggered it

Question 13

what activates the classical pathway

Answer 13

antibodies or pentraxins

Question 14

pentraxins

Answer 14

primitive form of Ig
- Pentameric serum proteins that participate in innate immunity and can also activate the Classical pathway of complement

Question 15

pentraxins are important for

Answer 15

acute phase infections

Question 16

classical pathway

Answer 16

• Antibody binds to target antigen
• C1Q/R/S complex (proteolytic complex) binds to the Fc domain of antibody and C1R is activated by C1Q, C1R cleave activates C1S
• Conformational change as it binds to Fc which triggers proteolytic cascade that then heads down to the C3 convertase
• C1 cleaves C4
• C4B then binds to the cell surface and binds to C2
• C1S cleaves c2 bound to C4B and C3 convertase is produced
• C3 convertase then cleaves C3 to C3a and C3b which have effector actions

Question 17

collectins and ficolins (as part of the lectin pathway)

Answer 17

 Bind to carbohydrates
 epithelium of the respiratory tract is lubricated by a layer of phospholipids and proteins known as surfactants
- Two of these, Surfactant Protein-A (SP-A) and Surfactant Protein-D (SP-D) are Collectins and function as opsonins,
coating microorganisms (e.g. Pneumocystis in AIDs patients - Lecture 8) and stimulating uptake by phagocytes

Question 18

what bind to carbohydrates

Answer 18

collecitins and ficolins

Question 19

the collectin family

Answer 19

• The Collectin family also includes Mannose-Binding Lectin (MBL) - binds to mannose-containing carbohydrates on surface of viruses, bacteria and fungi

Question 20

ficolins bind to

Answer 20

N-acetylglucosaine (not found in humans)

Question 21

polypeptide chain of the collectin family of proteins consists of

Answer 21

an amino-terminal cysteine-rich region followed by a collagen-like region, an a-helical neck region and a carboxy-terminal globular domain (a C-type lectin known as the carbohydrate recognition domain [CRD])
- polypeptide chain trimerise

Question 22

both MBL and SP-A are

Answer 22

hexameric structures

- multiple array of CRDs give high affinity binding to polysaccharides ligands in microbial cell walls

Question 23

In the collectin pathway the particle recognition is translated into immune action

Answer 23

1. By phagocytes, which are stimulated to internalize bound microorganisms or,
   
   2. By conformational changes in the collectin that activate pre-bound protease subunits and initiate the complement cascade

Question 24

when six proteins of the collectin family come together

Answer 24

they bind to mannose- this causes conformational change which pulls legs apart and this triggers proteases which starts the cascade

Question 25

lectin pathway after collectin bound to mannose and causes conformational change

Answer 25

1) MASP (mannose-binding, lectin Associated Serine protease) in the legs are activate during conformational change when mannose binds
2) MASP-2 cleaves C4
3) C4b attaches to cell surface
4) C2 binds to C4b
5) MASP-2 cleaves C2 bound to C4b
6) Which produces C3 convertase
7) This causes C3 to be cleaved and this causes effector actions

Question 26

what is MBL

Answer 26

mannose binding lectin

Question 27

what are mannose binding lectins

Answer 27

a lectin that is instrumental in innate immunity[5][6] as an opsonin and via the lectin pathway

Question 28

what to MBLs facilitiate

Answer 28

MBL recognizes carbohydrate patterns, found on the surface of a large number of pathogenic micro-organisms, including bacteria, viruses, protozoa and fungi. Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system.

Question 29

MASPs are complexed with…

Answer 29

MBL in the blood is complexed with (bound to) another protein, a serine protease called MASP (MBL-associated serine protease).

Question 30

what do MASPs do?

Answer 30

when MBL binds to its target (for example, mannose on the surface of a bacterium), the MASP protein functions to cleave the blood protein C4 into C4a and C4b. The C4b fragments can then bind to the surface of the bacterium, and initiate the formation of a C3-convertase

Question 31

the membrane attack complex..

Answer 31

a structure typically formed on the surface of pathogen cell membranes as a result of the activation of the host’s complement system

Question 32

structure and role

Answer 32

The membrane-attack complex (MAC) forms transmembrane channels. These channels disrupt the cell membrane of target cells, leading to cell lysis and death.

allows free diffusion of molecules in and out of the cell. If enough pores form, the cell is no longer able to survive.