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Flashcards in Innate Immunity Deck (133):
1

Is innate immunity specific or non-specific? Fast or slow?

Non-specific, fast

2

Is adaptive immunity immediate or later? Specific or not?

Slow, specific

3

What are the cells that are involved in innate immunity?

1. Phagocytes
2. Neutrophils
3. Natural killer T cells

4

What are the cells that are involved in adaptive immunity?

T and B lymphocytes

5

What are the cell receptors in innate immunity?

Fc & complement receptors, lectins (Non-polymorphic), Pattern recognition receptors

6

What are the cell receptors in adaptive immunity?

B and T cell receptors (diverse)

7

What are the circulating molecules in innate immunity?

Complement (non- polymorphic)

8

What are the circulating molecules in adaptive immunity?

Immunoglobulins (diverse)

9

What are the soluble mediators of innate immunity?

Macrophage-derived cytokines, other acute phase reactants, systemic effects, inflammation

10

What are the soluble mediators of adaptive immunity?

Lymphocyte-derived factors (local growth and regulation)

11

What is the recruitment mechanism in innate immunity?

Recruitment

12

What is the recruitment mechanism in adaptive immunity?

Clonal expansion

13

Which type of immunity has memory?

Adaptive

14

Which type of immunity it variable within indiiduals?

Adaptive--innate response is largely the same

15

What are PAMPs?

pathogen-associated molecular patterns (e.g single stranded DNA, RNA etc).

16

What is lipopolysaccharide (LPS, endotoxin)?

A pattern expressed by gram negative bacteria

17

What are damage associated molecular patterns?

endogenous molecules that are produced by, or released from damaged and dying cells, activating the innate immunity

18

What are toll-like receptors?

A subset of pattern recognition receptors

19

What is TLR4?

Toll-like receptor that binds to LPS, a gram negative protein

20

Where are PRRs found?

in different cellular locations; some are on the cell membrane, others in endosomes, and others in the cytoplasm

21

What does PAMP/TLR activate?

NFkB and IRFs which leads to inflammation antiviral state

22

What are inflammasomes?

Hyperactivation of the inflammasome results in autoinflammatory syndromes which can be treated with IL-1 antagonists.

23

True or false: The receptors of the innate immune system are encoded in germline DNA and recognize conserved patterns on pathogens

True

24

What is the complement system?

a system of non-polymorphic soluble proteins that form a proteolytic cascade important in clearance of a variety of pathogens

25

What are cytokines?

soluble molecules that form a mechanism for communication in the immune system. They can facilitate innate and adaptive immunity.

26

How does recruitment of lymphcytes occur? Leukocytes?

Lymphocytes - clonal expansion of specific lymphocyte populations

Leukocytes - Recruitment of leukocytes to sites of infection

27

Which type of immunity improves over time?

Adaptive

28

What are pattern recognition patterns (PRRs)?

Structures that a on leukocytes that recognize microbial pathogens

29

What are Pathogen-associated molecular patterns (PAMPs)?

molecular structures that are produced by microbial pathogens

30

PAMPs are ligands for what?

PRRs

31

What is the example of a PAMP used in class?

Lipopolysaccharide (LPS, endotoxin), which is on Gram-negative bacteria

32

What allows the innate immune system to recognize damaged self cells?

Damage associated molecular patterns (DAMPs). These are expressed by cells consitutively, so long as there is no damage to the cell

33

What are Toll-like receptors?

A protein recognition receptor on leukocytes that enables recognize specific PAMPs

34

What is the function of TLR4?

Recognizes the LPS molecule on Gram-negative bacteria, resulting in production of pro-inflammatory cytokines from monocytes and macrophages.

35

Where are PRRs found? Why is this significant?

some are on the cell membrane, others in endosomes, and others in the cytoplasm.

This is significant because both intracellular and extracellular pathogens can activate PRR.

36

What are NOD-like receptors?

Cytosolic PRR that trigger activation of innate immunity

37

What is the NLRP family

a subfamily of NLR that are important in generation of the proinflammatory cytokine IL-1 via activation of the inflammasome

38

What are inflammasomes?

Proteins that are responsible for activation of the inflammatory process

39

What are the three mechanical barriers the body has to prevent infection?

1. Epithelial cells
2. Longitudinal flow of air
3. Movement of mucus

40

What type of junctions are between epithelial cells?

Tight junctions

41

What are the two families of antimicrobial peptides that epithelial cells produce?

1. Defensins
2. Cathelicidins

42

What is the mechanism of action of Defensins/cathelocidins?

These molecules are directly toxic to microbes and also activate leukocytes to promote inflammation

43

What prevent colonization of microbes in the GI and GU tract?

Low pH

44

What are lysozomes?

antimicrobial enzymes that break down bacterial cell walls

45

What is the commensal bacteria that normally reside in/on epithelial barriers

The microbiome

46

What is the benefit of the presence of a microbiome on human epithelial cells?

Prevents the colonization of the epithelial tissue by other microbials

47

What are the three professional phagocytic cells?

Neutrophils
Monocytes/macrophages
Dendritic cells

48

Where do the professional phagocytes originate from?

Bone marrow

49

What are the first cells that are present in the sites of infection?

Neutrophils

50

What percent of circulating leukocytes are neutrophils?

59%

51

How long do neutrophils live for?

24-48 hours

52

What differentiates monocytes from macrophages?

Monocytes are circulating cells, whereas macrophages are the cells when they are present in tissues, where they differentiate

53

How long do macrophages live for?

Months

54

Where are macrophages found?

In all tissues

55

How are macrophages named?

Based on their location (microglia, alveolar macrophages etc)

56

What is the first step in the generation of an immune response?

Phagocytosis of an antigen by professional phagocytes

57

What are intraepithelial lymphocytes?

lymphocytes found in the epithelial layer of mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract. However, unlike other T cells, IELs do not need priming. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT)

58

What is phagocytosis needed for, beside the immune system?

Development and tissue homeostasis

Also eat dead neutrophils

59

What are polymorphonuclear-leukocytes (PMNs)?

Neutrophils

60

Where are sinusoidal macrophages found?

In the spleen

61

What happens after microbes bind to phagocyte receptors?

Actin is rearranged to engulf microbe

62

What are dendritic cells? What is their function?

Phagocytic cells that exists in tissues.

Their main function is to process antigen material, and present it on the cell surface to the T cells of the immune system in lymph nodes. They act as messengers between the innate and the adaptive immune systems.

63

What are opsonins?

Soluble proteins that recognize phagocytic targets and are then recognized by specific receptors on phagocytics cells

64

What are the two major classes of opsins?

Complement and antibodiy

65

What are the two specific opsins discussed in class?

C3 -complement
IgG - antibody

66

What is the receptor molecule for IgG?

Fc(gamma)RI

67

What is the intracellular vesicle formed following engulfment of a particle ?

Phagosome

68

What happens to the phagosome once it is inside the cytoplasm?

Fuses with a lysosome

69

What is the pH of lysosomes?

3.5-4.5

70

How is TB able to survive the acidic phagosome?

prevent fusion of the phagosome and lysosome and inhibit acidification of the phagosome

71

What are the ROS that the body uses in defense?

superoxide
hydrogen peroxide
singlet oxygen
hydroxyl radical
Hypohalite (OCl)

72

How have bacteria evolved to avoid the ROS that the body produces?

expression of enzymes like catalase

73

How is superoxide produced in the body?

Via NADPH oxidase

74

What happens when individuals lack NADPH oxidase?

Developed chronic granulomatous disease (CGD), where they are more susceptible to bacterial infections

75

What type of cells express NADPH oxidase?

PMNs (neutrophils)

76

How are toxic nitrogen oxides produced?

from activated macrophages especially following macrophage activation with proinflammatory cytokines such as TNF.

77

What is the enzyme that is produced by both macrophages and epithelial cells that breaks down bacterial cell walls?

Lysozyme

78

What are cytokines? What is the effect on macrophages?

Cell signalling molecules

Upregulates NO production, and the killing capacity of macrophages

79

What is IL-12?

a cytokine released by macrophages that activates otherc ells types, such and lymphocytes

80

What are natural killer cells?

Large granular lymphocytes that are important in killing of virally infected cells and tumor cells

81

When are natural killer cells particularly important?

early stages of viral infection prior to induction of adaptive immune response

82

NK cell inhibitory receptors bind to what molecules?

MHC class I

83

What are MHC Class I molecules?

A molecule that is expressed on all healthy nucleated cells, and prevents killing by natural killer cells

84

What happens to MHC Class I molecules as a cell becomes infected?

Downregulated, leading the virally infected cell or tumor cell susceptible to killing by NK cells

85

What is Fcγ receptor III (CD16)?

A receptor for natural killer cells that binds to antibody (IgG) that binds to target cells

86

What is the process through which natural killer cells kill infected cells?

antibody dependent cell mediated cytotoxicity (ADCC)

87

What is perforin?

A protein found in NK cell granules that is released when prompted, and kills target cells

88

What are granzymes?

Granule proteins that translocate into the cytosol of a NK cell's target, and cause programmed cell death

89

What is cytokine IL-2?

A cytokine that activated NK cells to kill, turning them into lymphocyte activated killer cells (LAK)

90

What are lymphocyte activated killer cells (LAK)?

NK cells that have been activated by IL-2, and kill tumor cells

91

What is cytokine IL-12?

Cytokine produced by activated macrophages, and stimulates NK cells to produce interferon γ which is the most potent macrophage activating cytokine

92

How do NK cells cells facilitate macrophage activation and killing of phagocytosed micro-organisms?

Via interferon γ

93

What are the three types of innate lymphoid cells?

ILC1, 2, and 3

94

What is the function of innate lymphoid cells?

Produce specific cytokines

95

What are the three main effector functions of complement?

Opsonization
Leukocyte migration
Lysis of pathogens

(Therefore, when a microbe enters the body, the complement system facilitates clearance of the microbe by enhancing phagocytic clearance, recruiting additional leukocytes to the site of infection, and directly killing the pathogen. )

96

The complement opsonins are large proteolytic fragments of what?

complement components C3b and C4b

97

What is the function of C3b and C4b?

covalently attach to the surface of pathogens via a reactive thioester bond to opsinify it

98

Do NK cells specifically recognize antigen that causes disease?

No--only the virus infected cells

99

What stimulates keuocyte migration?

Chemicals called chemokines

100

What are the complement chemokines?

Anaphlyatoxins

101

What is C3a?

A chemokine that triggers leukocyte recruitment

102

What is C3b?

an opsonin that stimulate phagocytosis

103

What is C3?

Precursor to C3a/b, and is central to all complement pathways

104

What is the mechanism by which lysis of pathogens can be brought about?

The terminal components of complement: C5, C6, C7, C8 and C9 form a pore in the membrane of pathogens (mostly Gram-negative bacteria) resulting in lysis of pathogens

105

What are the three pathways through which complement is activated?

1. Classical
2. Alternative
3. Lectin

106

What is the result of all three complement activation pathways?

1. opsonization
2. leukocyte recruitment
3. pathogen lysis

107

Where do the three pathways of complement activation converge? What happens next?

At C3, which is cleaved by C3 convertase into C3a and C3b

108

C3b also associates with the C3 convertase to form what?

a C5 convertase which cleaves C5 into C5a and C5b

109

What is the function of C5b?

C5b remains associated with the microbial surface to form the membrane attack complex

110

What is the classical complement activation pathway?

Initiated by antibodies to produce C1.

111

What is C1?

The complement activating protein in the classical pathway,consisting of the recognition component, C1q, and two molecules each of the serine proteases C1r and C1s.

112

How it the lectin pathway initiated?

Sugar residues on microbes are recognized and start the pathway, leading to

113

Will free antibodies activate the complement cascade?

No

114

Which is more effective at activating the classical pathway, IgM or IgG?

IgM

115

What is the initiation component of the classical complement pathway?

C1

116

Where does the alternative complement pathway take place? When does it occur?

On the microbial surface

Happens constitutively, but the C3 will be degraded if there are no bacteria around

117

What is the effect of the regulator protein CD59?

prevents the binding of C9 such that the membrane attack complex cannot form

118

What is the effect f decay accelerating factor?

dissociates the C3 convertases to prevent all effector functions of complement

119

What is paroxysmal nocturnal hemoglobinuria? What causes it?

A condition where there is intravascular lysis of red blood cells by complement.

This is caused by deficiencies in either CD59, or decay accelerating factor

120

What is the inhibitor for the classical complement activation?

C1 inhibitor

121

What is the activator protein for the alternative pathway?

C3

122

What are the activator proteins for the lectin pathway?

MASP1 and 2

123

What is hereditary angioneurotic edema (HAE?) What causes it?

A condition where there is swelling of skin and larynx which can be potentially life threatening.

This is caused by a deficiency in C1 inhibitor

124

Deficiencies in C1, C2, C4 or other early classical complement pathway components leads to what?

Autoimmune diseases, like lupus

125

Deficiencies in early components of the lectin pathway results in what?

increased susceptibility to bacterial infection

126

Deficiency in Factor D and Factor P, early components of the alternative pathway leads to what?

increases susceptibility to infection with pyogenic bacteria and Neisseria

127

Deficiency in C3 affects all three complement pathways and leads to what?

increased susceptibility to pyogenic bacteria and Neisseria

128

Deficiency in the terminal components of complement, C5b- 9, results in what?

The inability to generate the membrane attack complex and increased susceptibility to Neisseria infection.

129

Can cytokines act at a distance?

Yes

130

What is the main method of communication in the immune system?

Cytokines

131

What is IFNγ?

Cytokine produced by activated T-cells to promote macrophage activation

132

What is IL-12?

A cytokine produced from activated macrophages that causes NK cells to make more IFNγ

133

Type 1 interferon (IFN) is composed of  and  IFN and is produced in response to viral infection. What are its effects? (3)

• Inhibit viral replication via a paracrine action.
• Enhance the cytolytic capability of NK cells
• Increase cellular expression of class I MHC molecules (Class I MCH is important for host defense against viral infection.)