complement system

Question 1

Complement proteins (around 50) circulate in
our blood but are _. but _ when cleaved

Answer 1

inactive
active

Question 2

rule of 3:

Answer 2

C3 convertase: c3 into c3a and c3b
3 activation pathways
3 effector functions: lysis, opsonisation, signalling

Question 3

cleaved components:
a is _
b is _

Answer 3

the smallest fragment
the largest fragment

Question 4

the _ does a _ attack on the _

Answer 4

C3b nucleophilic
thioester bond

Question 5

Classical Pathway: Activated by _ bound to antigens and by _.
Protease activated upon binding, _ cleavage
_ binds _ to the pathogen surface.

Answer 5

antibodies
C-reactive protein
C4
C4b covalently

Question 6

Lectin Pathway: Triggered by _ like MBL (_), _, and _ that bind to specific carbohydrate structures on the surface of pathogens.
_ is cleaved and _ binds covalently to pathogen surface.
_ cleavage –> _ binds to _ forming

Answer 6

pattern recognition molecules
Mannose-binding lectin
Ficolin
Collectin
C4
C4b
C2
C2a
C4b
the classical C3 convertase

Question 7

High density of _ deposition changes
C3 convertases into C5 convertase. which leads to the _

Answer 7

C3b
membrane attack complex (MAC). c5b joins C6-C9 to lyse the pathogen

Question 8

High density of C3b deposition changes
C3 convertases into _ convertase

Answer 8

C5

Question 9

Two anaphylatoxins are generated during
complement activation:
_
anaphylatoxins act on _ to _ leading to _ and _

Answer 9

C3a and C5a
blood vessels
increase blood vessels (vascular) permeability
increased fluid leakage from blood vessels and extravasation of other complement proteins and other plasma proteins.
migration of macrophages and neutrophils from blood vessels into tissues.

Question 10

1. Opsonisation within _ minutes
2. Lysis after _ minutes
3. Cell death within _ minutes

Answer 10

1-2
2
3-4

Question 11

C3b is tightly controlled by _

Answer 11

host cells

Question 12

Regulating C3bBb:

Answer 12

• Decay accelerating factor (CD55)
• Membrane co-factor protein (CD46)
• Complement Receptor 1 (CD35)

Question 13

Inactivating C3b -> together with Factor I

Answer 13

• MCP (CD46)
• Complement Receptor 1 (CD35)

Question 14

_ inhibits MAC formation (prevents _)

Answer 14

CD59
C9 to bind

Question 15

the alternative pathway is _

Answer 15

non-specific because can be activated directly by pathogen surfaces without the need for prior antibody recognition

Question 16

Factor H, a key regulator in the _ of the complement system. Factor H is an _ protein in the fluid phase (_) and functions by:

Competing with _: for binding sites on _, preventing the formation of the _, which is crucial in the complement cascade.

Accelerating the _.

Co-factoring _:to cleave C3b into _, thus _ it and preventing further progression of the complement cascade.

Dual Action: Factor H acts both in the _ and on _, helping to protect host cells from accidental damage by complement activation.

Answer 16

Alternative Pathway (AP)
abundant
circulates freely

Factor B (FB)
C3b
C3 convertase
Decay of C3 Convertase (C3bBb)
for Factor I
iC3b
inactivating
fluid phase
host cell surfaces

Question 17

excessive complement activation and sufficient regulation:

Answer 17

autoimmune diseases

Question 18

slightly excessive complement activation and slightly regulation:

Answer 18

hematological diseases

Question 19

sufficient complement activation and insufficient regulation:

Answer 19

kidney diseases

Question 20

excessive complement regulation and sufficient activation:

Answer 20

cancer

Question 21

excessive complement regulation and insufficient activation:

Answer 21

infections

Question 22

The complement system must be tightly regulated to prevent it from attacking the _. If there is a failure in this regulatory process—due to deficiencies in regulatory proteins like Factor H or I—the complement system can become _. This _ can lead to _, contributing to _.

Answer 22

body’s own cells
overactive
overactivity
an attack on the body’s own tissues
autoimmune diseases

Question 23

The _ is the final sequence of the complement system, leading to the formation of the Membrane Attack Complex (MAC). If there are deficiencies in the components of this pathway, such as in the _ (e.g., C5-C9), the body cannot form the MAC effectively.
This results in increased vulnerability to infections, particularly from organisms like Neisseria meningitidis, which causes _ disease. Normally, the complement system plays a crucial role in defending against this bacteria by killing it directly through the MAC.

Answer 23

terminal pathway
terminal complement proteins

meningococcal

Question 24

_, a central protein in the complement cascade, is a common target for these therapies because it is _ in the bloodstream, making it an accessible target for drugs aiming to inhibit complement activity.
For these therapies to be effective, they often need to _ the targeted component of the complement system. _ may not sufficiently reduce the activity to prevent disease symptoms or progression.

Answer 24

C3
plentiful
completely block
Partial blockage

Question 25

can inhibit _ as long as _
eg of drug:

Answer 25

C5
get accination
Eculizumab