Complement System Flashcards

1
Q

What is the complement cascade?

A

Enzymatic response to infection

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2
Q

What is purpose of pathways?

A
  1. Opsonises pathogens for phagocytosis by macrophages and neutrophils
  2. Produce MAC
  3. Produce anaphylatoxins
  4. Attract neutrophils to site of infection
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3
Q

What are the 3 main pathways of complement activation?

A
  1. Classical pathway
  2. Lectin or mannose-binding pathway
  3. Alternative pathway
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4
Q

What is the classical pathway activated by? What does it require?

A

Antigen-antibody complexes. Requires activation of adaptive immune system first

Activated when complement factor C1 binds to antibody-antigen complexes (generated by adaptive immune system)

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5
Q

What are most of the complement factors?

A

Serine proteases - similar to trypsin (digestive enzyme) but much higher specificity

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6
Q

How is the next factor activated in the classical pathway?

A

Limited proteolysis (one protein one cut)

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7
Q

Which by products of the CP are anaphylatoxins?

A

C3a, C4a and C5a

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8
Q

Which product of the

CP plays a role in opsonisation?

A

C3b

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9
Q

What are the steps of the CP?

A
  1. C1 cleaves C2 into C2a and C2b
  2. C1 also cleaves C4 into C4a and C4b
  3. C2a and C4b form a complex (C2a/C4b) which cleaves C3 into C3a and C3b
  4. C3b joins C2a/C4b complex forming a C2a/C4b/C3b complex which cleaves C5 into C5a and C5b
  5. C5b finally forms complex with C6, C7, C8 and C9 to produce MAC
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10
Q

What is function of MAC?

A

Membrane Attack Complex - perforates cell membrane of pathogens / virus-infected host cells

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11
Q

What is the lectin / mannose-binding pathway activated by?

A

Direct contact with pathogen - mannose binding lectin binds to mannose on pathogen surfaces

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12
Q

What is mannose-binding pathway based on?

A

Particular sugar (mannose) is found on cell membrane of many pathogens, but not on host cells

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13
Q

What protein binds mannose on pathogens?

A

Mannose Binding Lectin (MBL)

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14
Q

What proteases do MBL bind?

A

MASP 1 and 2

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15
Q

MBL and MASP complex cleaves what factors?

A

C2 and C4, forming C2a and C2b and C4a and C4b

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16
Q

What pathogens express mannose and bind MBL to activate the lectin pathway?

A
  1. Yeast –> Candida albicans
  2. Viruses –> HIV and influenza
  3. Bacteria –> Salmonella and Streptococci
  4. Parasites –> Leishmania
17
Q

What parts of the lectin pathway and classical pathway are identical?

A

C3-C9

18
Q

What is the alternative pathway activated by?

A

Direct contact with pathogen

19
Q

Alternative pathway involves auto-activation of C3 at a very low rate. How does this come about?

A

C3 is very unstable so can activate itself, forming C3b

20
Q

What does auto-activated C3b bind to?

A

Some C3b binds to pathogens

Some binds to factor B

Some binds to properdin

This rapidly activates more C3 and C5

21
Q

What part of alternative pathway are identical to lectin and classical pathway?

A

C6-C9

22
Q

What are anaphylatoxins?

A

By products - C3a, C4a and C5a (C3b, C4b and C5b play main role)

23
Q

What is function of anaphylatoxins?

A
  1. Trigger degranulation of endothelial cells, mast cells and phagocytes
  2. Cause smooth muscle contraction and enhance vascular permeability
  3. Attract neutrophils
24
Q

What do C3a and C5a also act as?

A

Chemoattractants

25
Q

What is purpose of chemoattractants?

A

Attract and activate neutrophils

26
Q

What do mast cells release?

A

Histamine

27
Q

What is benefit of smooth muscular contraction and enhanced vascular permeability?

A

Easier for neutrophils and NK cells to infiltrate infected tissue

28
Q

What factor is involved in opsonisation?

A

C3b

29
Q

What is opsonisation?

A

Pathogens are labelled to increase recognition by phagocytes - renders bacteria more susceptible to phagocytosis

30
Q

C3b is cleaved on bacterial surface to what? How does this assist phagocytosis?

A

iC3b

Macrophage membrane contains receptors for iC3b as iC3b is recognised

31
Q

What is name of complex/enzyme that C2a and C4b form?

A

C3 convertase

32
Q

What forms MAC?

A

C5b forms complex with C6, C7, C8 and C9 to form MAC