Block B Part 2: Soluble Mediators, Complement and Cell Mediated Immunity Flashcards

1
Q

What are 4 examples of soluble blood components?

A

Complement
Antimicrobial proteins (listed below)
Lactoferrin
Bactericidal (AKA permeability-increasing protein)
Defensins
(Lecture 4, Slide 3)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What does lactoferrin do?

A

Bind iron
(Lecture 4, Slide 3)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What form are complement and antimicrobial proteins often present in in the blood?

A

An inactive form
(Lecture 4, Slide 3)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What puts complement and antimicrobial proteins in the blood into their active form?

A

An immune response
(Lecture 4, Slide 3)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Are soluble mediators site specific?

A

They often are but not always
(Lecture 4, Slide 4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are defensins?

A

A family of antimicrobial proteins
(Lecture 4, Slide 5)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What 2 classes are defensins divided into?

A

α-defensins and ß-defensins
(Lecture 4, Slide 5)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are 2 ways that α-defensins are produced?

A

They are secreted by Paneth cells in the small intestine and produced by neutrophils
(Lecture 4, Slide 5)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are 2 ways that ­ß-defensins are produced?

A

They are continuously secreted at mucosal surfaces for protection and are produced by a broad range of epithelial cells
(Lecture 4, Slide 5)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are cathelicidins?

A

Natural antimicrobial proteins
(Lecture 4, Slide 6)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are 2 places cathelicidins are constantly produced?

A

Neutrophils and macrophages
(Lecture 4, Slide 6)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are cathelicidins produced in response to?

A

Infection by keratinocytes (Outer layer skin cells) and epithelial cells in the lungs and intestine
(Lecture 4, Slide 6)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are cathelicidins synthesised as?

A

Precursor proteins
(Lecture 4, Slide 6)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How are cathelicidins cleaved into 2 peptides?

A

Proteolytically
(Lecture 4, Slide 6)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does proteolytically mean?

A

The process of breaking down or cleaving protein through the action of enzymes called “proteases” or “peptidases”
(Lecture 4, Slide 6)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the only cathelicidin gene identified in humans?

A

CAMP - cathelicidin antimicrobial peptide
(Lecture 4, Slide 6)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is lysozyme?

A

A proteolytic enzyme contained inside of lysosomes (membrane-bond organelle)
(Lecture 4, Slide 7)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What layer of gram-positive bacteria does lysozyme degrade?

A

The peptidoglycan layer
(Lecture 4, Slide 7)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does lysozyme degrading the peptidoglycan layer of gram-positive bacteria do to them?

A

It makes them burst open under their own internal pressure
(Lecture 4, Slide 7)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why is lysozyme inactive against most gram-negative bacteria?

A

As it cannot penetrate the outer membrane to get to the peptidoglycan layer
(Lecture 4, Slide 7)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Who identified the complement system in 1895?

A

Jules Bordet
(Lecture 4, Slide 8)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the complement system?

A

A integrated system of approximately 30 soluble fluid phase and membrane proteins
(Lecture 4, Slide 8)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the plasma components of the complement system a part of?

A

Proteolytic cascades
(Lecture 4, Slide 8)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the 4 functions of the complement system?

A

Induces acute inflammation
Opsonises (marks) bacteria for phagocytosis
Bactericidal (kills bacteria) by inducing osmotic lysis (bursting of a cell due to osmotic pressure changes)
Facilitates removal of dead/apoptotic cells
(Lecture 4, Slide 9)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What does a “C” in front of proteins associated with the complement system mean?

A

Protein is associated with the classical and Mannan-Binding-Lectin (MBL) pathways
(Lecture 4, Slide 10)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are complement proteins cleaved into?

A

1 large (usually “b”) and 1 small (usually “a”) peptide
(Lecture 4, Slide 10)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What letters are used in front of complement proteins of the alternative pathway?

A

B or D etc
(Lecture 4, Slide 10)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What 4 things does C1q recognise?

A

Gram-negative bacteria
Some viruses
Damaged cells
Altered Proteins or antibodies bound to antigens
(Lecture 4, Slide 14)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What does C1q induce after recognising a threat in the classical pathway of the complement system?

A

The formation of the classical pathway C3 convertase (C4b2b)
(Lecture 4, Slide 14)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What 2 proteases does C1q bind with in the classical pathway of the complement system?

A

C1r and C1s
(Lecture 4, Slide 14)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What does binding of C1q to C1r and C1s lead to in the classical pathway of the complement system?

A

C1r and C1s becoming activated
(Lecture 4, Slide 14)

32
Q

What do C1r and C1s do after becoming activated in the classical pathway of the complement system?

A

It cleaves C2/4 producing C3 convertase
(Lecture 4, Slide 14)

33
Q

What does the production of C3 convertase trigger in the classical and mannose-binding lectin pathway of the complement system?

A

The rest of the cascade
(Lecture 4, Slide 14)

34
Q

What is the first step of the Mannose-binding lectin pathway of the complement system?

A

A soluble PRRs (pattern recognition receptor); Mannose-binding lectin (MBL) or Ficolins binds to specific sugars that can be found on many bacteria, fungi and some viruses
(Lecture 4, Slide 15)

35
Q

What is Mannose-binding lectin (MBL) secreted by?

A

Hepatocytes
(Lecture 4, Slide 15)

36
Q

What does Mannose-binding lectin (MBL) or Ficolins binding to specific sugars activate in the Mannose-binding lectin pathway of the complement system?

A

MBL-associated serine proteases (MASPs 1/2)
(Lecture 4, Slide 15)

37
Q

What do MASPs 1 and 2 do after being activated in the Mannose-binding lectin pathway of the complement system?

A

They cleave C2/C4 to form C3 convertase
(Lecture 4, Slide 15)

38
Q

How can the alternative pathway of the complement system be initiated?

A

When a spontaneously activated complement component binds to the surface of a pathogen
(Lecture 4, Slide 16)

39
Q

What can the alternative pathway of the complement system act as?

A

An amplifier for all 3 pathways of the complement system
(Lecture 4, Slide 16)

40
Q

What percentage of complement activation does the alternative pathway make up?

A

~ 80-90%
(Lecture 4, Slide 16)

41
Q

What forms Membrane Attack Complex (MAC)?

A

Assembly of the terminal components of complement
(Lecture 4, Slide 17)

42
Q

What is the first step of formation of Membrane Attack Complex?

A

Cleavage of C5 by a C5 convertase to release C5b
(Lecture 4, Slide 17)

43
Q

What is the second step of formation of Membrane Attack Complex?

A

C5b binds C6, and then the C5b,6 complex binds C7
(Lecture 4, Slide 17)

44
Q

What is the third step of formation of Membrane Attack Complex?

A

The C5b,6,7 complex (C5b-7 complex) undergoes a conformational change, leading to exposure of a hydrophobic site on C7, which inserts into the lipid bilayer
(Lecture 4, Slide 17)

45
Q

What is the fourth step of formation of Membrane Attack Complex?

A

C8 and C9 bind to the C5b-7 complex and also insert into the lipid bilayer
(Lecture 4, Slide 17)

46
Q

What is the 5th and final step of formation of Membrane Attack Complex?

A

Polymerization of between 10 and 16 molecules of C9 into a pore forming structure, known as the Membrane Attack Complex
(Lecture 4, Slide 17)

47
Q

What are C3a and C5a?

A

Anaphylatoxins
(Lecture 4, Slide 18)

48
Q

What are 3 functions of C3a?

A

Can produce inflammation and induce mast cell degranulation and stimulates extravasation of leukocytes from the blood stream to surrounding tissues
(Lecture 4, Slide 18)

49
Q

What are 3 functions of C5a?

A

Can produce inflammation and can activate mast cells and neutrophils and can act as a potent chemoattractant
(Lecture 4, Slide 18)

50
Q

What is the function of C5b?

A

It is a strong inducer of the Membrane Attack Complex
(Lecture 4, Slide 18)

51
Q

What is C3b also known as?

A

Opsonin
(Lecture 4, Slide 18)

52
Q

What are 3 ways in which cell-mediated immunity protects the body?

A

Activates Macrophages and NK cells
Stimulates cytokine secretion
Activates antigen-specific cytotoxic T cells (CD8+)
(Lecture 5, Slide 6)

53
Q

What is cell-mediated immunity most effective in destroying?

A

Cells infected with viruses, intracellular bacteria or cancer
(Lecture 5, Slide 6)

54
Q

What line of defence is cell-mediated immunity?

A

Third
(Lecture 5, Slide 6)

55
Q

What are 4 types of T-cell?

A

T-helper cells (CD4+)
Cytotoxic T cells (T-killer)(CD8+)
T-suppressor cells
T-memory cells
(Lecture 5, Slide 8)

56
Q

What is the function of T-suppressor cells?

A

Suppresses the actions of activated T cells once the threat has ended
(Lecture 5, Slide 8)

57
Q

What do T-suppressor cells prevent?

A

Over reactivity of immune cells
(Lecture 5, Slide 8)

58
Q

What is the function of T-memory cells?

A

They create larger and faster responses upon repeated exposure to the same antigen - acquired immunity
(Lecture 5, Slide 8)

59
Q

What MHC Classes do helper and cytotoxic T cells have?

A

Helper T cells have both class I and II
Cytotoxic T cells only have class I
(Lecture 5, Slide 9)

60
Q

What is the function of MHC class I receptors?

A

Aids in differentiation between self and foreign cells and pathogens
(Lecture 5, Slide 9)

61
Q

What is the function of MHC class II receptors?

A

They are present on antigen-presenting cells alongside MHC-I. MHC-1 will present antigen whereas MHC-II will present phagocytosed pathogens
(Lecture 5, Slide 9)

62
Q

How do cytotoxic T cells, kill the pathogen?

A

They lyse the body’s own cells to get rid of abnormal cells or pathogen infected cells
(Lecture 5, Slide 11)

63
Q

What does lyse mean?

A

The breaking down or destruction of a cells membrane leading to a release of it’s contents
(Lecture 5, Slide 11)

64
Q

What do cytotoxic T cells require in order to lyse a cell?

A

Close contact
(Lecture 5, Slide 11)

65
Q

What can cytotoxic T-cells cause in addition to lysis?

A

Apoptosis of the target cell
(Lecture 5, Slide 11)

66
Q

What occurs in CD4+ Th1-dependent cytotoxic T cell generation?

A

The naive CD4+ (helper) T cell recognises its antigen on a antigen presenting cell and becomes activated and sends signals to cytotoxic T cells to cause them to proliferate and differentiate
(Lecture 5, Slide 13)

67
Q

What occurs in CD4+ Th1-independent Tc generation?

A

A naive CD8+ (cytotoxic) T cells recognises its antigen presenting on the MHC class I receptor of an antigen presenting cell and becomes activated leading to proliferation and differentiation
(Lecture 5, Slide 14)

68
Q

What 2 chemicals do cytotoxic T cells release to trigger lysis / apoptosis?

A

Perforin (for lysis)
Granzymes (a protease to trigger apoptosis)
(Lecture 5, Slide 15)

69
Q

Why may the delayed-type hypersensitivity response (Type 4 response) be required?

A

If cytotoxic T cell responses are not enough to eliminate all intercellular pathogens
(Lecture 5, Slide 16)

70
Q

What can an inappropriate inflammatory response cause?

A

Significant tissue damage or even death under certain circumstances
(Lecture 5, Slide 17)

71
Q

How is a delayed type hypersensitivity (type 4) response induced?

A

Certain antigens activate specific populations of helper T cells which secrete cytokines to induce a delayed type hypersensitivity response
(Lecture 5, Slide 17)

72
Q

What is recruited to the site of inflammation instead of neutrophils in a delayed type hypersensitivity response?

A

Macrophages
(Lecture 5, Slide 17)

73
Q

Why are macrophages recruited to the site of inflammation in a delayed type hypersensitivity response?

A

To kill phagocytosed microbes / pathogens
(Lecture 5, Slide 18)

74
Q

How is the magnitude of the delayed type hypersensitivity response increased?

A

Macrophages and helper T cells stimulate each other forming an amplification loop
(Lecture 5, Slide 19)

75
Q

What 2 cytokines contribute to macrophage activation in a delayed type hypersensitivity response in the presence of IFN-γ?

A

TNF-α (tumour necrosis factor) and IL-2 (interleukin-2)
(Lecture 5, Slide 19)

76
Q

What retains macrophages at the delayed type hypersensitivity response and how is it produced?

A

Macrophage Inhibition Factor (MIF) secreted by Th cells
(Lecture 5, Slide 19)

77
Q

What happens upon antigen elimination in delayed type hypersensitivity responses?

A

Macrophages no longer stimulate Th cytokine production
(Lectures 5, Slide 19)