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Test 1 IBI > B3.016 - Complement > Flashcards

B3.016 - Complement Flashcards

1
Q

What is the complement system

A

a group of interacting proteins that are cleaved in sequence during complement activation to yield biologically active peptides

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2
Q

How is the alternative pathway triggered

A

B and C3

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3
Q

Which pathway is part of innate immunity

A

Alternative and pectin

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4
Q

How is the classical pathway triggered

A

By antibodies bound to microbes

C2 and C4

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5
Q

How is the lectin pathway triggered

A

MBL binds to terminal mannose residues on microbial cell surface glycoproteins
C2 C4

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6
Q

What do the C3, C2 and C4 do?

A

Help with cleavage of C3 to C3a and C3b

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7
Q

What does C3a do

A

Stimulates inflammation

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8
Q

What does C3b do

A

Deposited on microbe. Helps with opsonization and phagocytosis

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9
Q

What does C5 do

A

Cleaved into C5a and C5b

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10
Q

What does C5a do

A

Helps with inflammation

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11
Q

What does C5b do

A

Combines with C6,C7,C8 and multiple C9s to make MAC

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12
Q

What are the anaphalotoxins

A

C3a and C5a

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13
Q

What do C3a and C5a do

A

Mediators of inflammation

Stimulate mast cells to release their granules and induces urticaria (hives) via histamine release

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14
Q

What is the most common complement related deficiency

A

C2 deficiency

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15
Q

What can be used as an indicator of a disease state with regards to complement components

A

C3 and C4 levels to see if they’re being consumed

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16
Q

What component of complement binds to microbes

A

C3b

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17
Q

What can C3b binding to the microbe cause

A
  1. ) Phagocytosis and killing of microbe
  2. ) Osmotic lysis of microbe by activating later stages of complement
  3. ) destruction of microbe by leukocytes by release of C3a and C5a to recruit leukocytes
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18
Q

What makes up the MAC

A

C5b, C6, C7, C8, many C9s

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19
Q

What pathway does C3d come from

A

Alternative

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20
Q

What does C3d do

A

Recognized by B cell complement receptor 2 (CR2)

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21
Q

Deficiency in late stage MAC production causes what disease

A

Neisseria infections

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22
Q

What are C3 deficiencies a cause of

A

Bacterial infections, may cause early childhood death

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23
Q

What does a deficiency in the MAC complex cause

A

Disseminated Neisseria infections (meningitis)

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24
Q

What does C5a do

A

Chemotaxis of neutrophils

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25
Q

what do C3b and iC3b do

A

Opsonophagocytosis

Clearance of immune complexes

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26
Q

What do C3a, C4a, and C5a do

A

Danger signaling

27
Q

What do C5b, C6, C7, C8, C9n do

A

Lysis of cell

28
Q

What does C3d do?

A

Coactivation of B cells

29
Q

What does C1 inhibitor (C1 esterase) do

A

Inhibits the classical pathway

30
Q

What does MASP 1,2 do

A

Inhibits the MBL pathway

31
Q

What does Anaphylatoxin inhibitor do

A

Degrades C3a, 4a, 5a to reduce inflammation

32
Q

What does Factor 1 do

A

Cleaves C3b to iC3b to block the C3b part of pathway leading to opsonization of pathogens w

33
Q

What does S protein do

A

Blocks insertion of MAC into host cell membrane

34
Q

Normally C1q binds to what to cause what

A

Binds to antigen complexed antibodies resulting in activation of C1r2s2

35
Q

What does C1INH do

A

Prevents C1r2s2 binding and becoming proteolytically active

36
Q

What does C1 INH do

A

Prevents C1r2s2 from becoming proteolytically active

37
Q

What among inflammatory mediators can cause cutaneous swelling

A

Histamine related from mast cells

Bradykinin produced from kallikrein cascade

38
Q

How do histamine and bradykinin act

A

Increase vascular permeability and vasodilation

39
Q

Itchiness is indicative that a reaction is mediated by what

A

Histamine

40
Q

Non itchiness and non erythematous area indicates a reaction is mediated by what

A

Bradykinin

41
Q

Longer attacks indicate what about the cause

A

Its non histamine related

42
Q

True allergic reactions should what

A

Be reproducible and consistent

43
Q

Allergic reactions are mediated by what

A

Mast cells

44
Q

What labs do you get to check the components of Mast cell mediated allergic reactions

A

Tryptase

Histamine

45
Q

What is tryptase

A

A protease released by mast cells that degrades in 4-6 hours

46
Q

How quickly does histamine degrade

A

Within 15 minutes

47
Q

What labs do you get to see if a reaction is bradykinin mediated

A

Complement studies: C2, C4, C1 esterase inhibitor level and fxn

48
Q

What does factor 12 do

A

Activates kallikerian to eventually yield bradykinin

Activates plasmin and uses up complement components

49
Q

A C1 esterase inhibitor defect means what

A

The complement system is going unopposed and increased bradykinin leading to angioedema

50
Q

What therapeutic intervention could also increase bradykinin levels

A

ACE inhibitors

51
Q

ACE inhibitors are prescribed for what

A

Hypertension

52
Q

How long does it take for angioedema caused by bradykinin levels to resolve

A

3-5 days

53
Q

Episodes of hereditary angioedema can happen where

A

Anywhere on the body

54
Q

Are patients with hereditary angioedema at risk for infection?

A

No, complement cascade is redundant

55
Q

What is the pathophys of hereditary angioedema

A
  1. ) absence of C1 esterase inhibitor permits ongoing cleavage of C2 and C4 leading to overconsumption
  2. ) C2b is further cleaved to a C2 kin in peptide which alters vascular permeability
  3. ) C1 esterase inhibitor also regulates fibrinolytic and bradykinin systems which leads to vascular permeability and vasodilation
56
Q

Describe type 1 HAE (low levels of what, age of onset, treatments)

A

Low or no C1 INH levels or fxn
Low C2 or C4 from overconsumption
Age of onset 0-20
Can be treated by C1 INH replacement, androgens, Bradykinin inhibitors

57
Q

Type 2 HAE describe

A

Same as Type 1 except normal levels of C1 INH, but function is an issue

58
Q

HAE type 3 describe

A

Everything is normal, runs in families
Age of onset 1-63
Unsure of treatments
We think factor 12a

59
Q

Acquired angioedema describe

A

Low levels of everything due to autoimmune consumption/inhibition
Older people with lymphoma or autoimmune disease
Treat underlying defect
Age of onset over 20

60
Q

Therapeutic options for angioedema

A

Supportive care

Anti emetics for GI attacks, IV fluids for dehydration

61
Q

What medications are given for acute settings

A

Fresh frozen plasma
C1 esterase inhibitor replacement products
Kallikrein inhibitors
Bradykinin receptor antagonists

62
Q

What is ecallantide

A

Kallekrein inhibitor

63
Q

What is Icatibant

A

Bradykinin receptor antagonists

64
Q

Would a bradykinin receptor antagonists work for ACE inhibitor angioedema

A

Yes it should

Test 1 IBI (8 decks)

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