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Core Concepts in Immunology > Lecture 2. Inflammation and Innate Defences > Flashcards

Lecture 2. Inflammation and Innate Defences Flashcards

1
Q

What is the timeline of a primary immune response?

A
  1. Pre-formed/innate response
  2. Induced inflammatory response
  3. Specific adaptive response
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2
Q

What does the induced inflammatory response rely on ?

A

Recognition of danger

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3
Q

Why does the adaptive immune response occur late ?

A

Lymphocyets specific for the invading pathogen must first undergo clonal expansion

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4
Q

Where are naive T-lymphocytes found ?

A

Lymph nodes

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5
Q

What are the general PAMPs ?

A
  1. LPS
  2. dsRNA
  3. CpG
  4. DNA
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6
Q

What are the two cell types involved in the innate immunity ?

A
  1. Macrophages
  2. Dendritic cells
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7
Q

What are the pathogen recognition receptors ?

A
  1. TLRs
  2. CLRs
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8
Q

What are some specific antigens involved in the adaptive immunity ?

A
  1. PHA
  2. Ovalbumin
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9
Q

What are the cells involved in the adaptive immunity ?

A
  1. T cells
  2. B cells
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10
Q

What does the innate immunity form ?

A

One of the earliest responses to infection

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11
Q

What does the innate immune system do ?

A

Distinguish self from non-self

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12
Q

What does the innate immune system activate ?

A

Adaptive immune syste - if pathogen bypasses innate host defences

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13
Q

What function does the innate immunity carry out ?

A

A delaying function

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14
Q

What is the delaying function of the innate immune system ?

A

Keeping pathogen numbers in check while adaptive immune system gears up

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15
Q

What is the innate immune system mediated by ?

A
  1. Innate immune cells
  2. Soluble effector proteins
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16
Q

What are the three things involved in the innate immunity ?

A
  1. Physio-chemical barriers
  2. Humoral components
  3. Cellular components
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17
Q

What does the induced inflammatory response do ?

A

Delivers cells and plasma proteins to infection sites

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18
Q

What is the insult of the induced inflammatory response ?

A

Infection or damage

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19
Q

What are the resident cells of the induced inflammatory response ?

A
  1. Macrophages
  2. Dendritic cells
  3. Epithelial cells
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20
Q

What are the messengers involved in the induced inflammatory response ?

A
  1. Cytokines - IL1, TNF
  2. Chemokines - CXCL8
  3. Prostaglandins
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21
Q

What is an epithelial cell ?

A

Local cell

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22
Q

What are cytokines ?

A

Driver of inflammation

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23
Q

What are the recruited cells in the induced inflammatory response ?

A
  1. Monocytes - macrophages and dendritic cells
  2. Neutrophils
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24
Q

What is the first thing found at the site of infection ?

A

Neutrophils

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25
Q

What is the second thing found at an infection site ?

A

Mononucletide

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26
Q

What does CsF1 determine ?

A

Difference in macrophage an mononucleoties

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27
Q

What do neutrophils do ?

A

Have a short life, degranulate, netosis and expel nucleus

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28
Q

What are the effector mechanisms involves in the induced inflammatory response ?

A
  1. Immune signalling
  2. Cytokine production
  3. Phagocytosis
  4. Antigen presentation
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29
Q

When does the induced inflammatory response have an adaptive response ?

A

In the presence of specific antigens

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30
Q

What happens as a result of effector mechanisms and addaptive responses ?

A

Resolution of inflammation

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31
Q

What are the routes of infection ?

A
  1. Inhalation
  2. Direct contact
  3. Invasion
  4. Ingestion
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32
Q

What is infection ?

A

The invasion and multiplication of a pathogen in a susceptible host

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33
Q

What is invasion facilitated by ?

A
  1. Toxins
  2. Factors encoded by pathogens or immunosupression
  3. Susceptibility in the host
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34
Q

When does infectious disease manifest ?

A

When infection results in clinical pathology or tissue damage

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35
Q

What are the epithelial surfaces involved in barriers to infection ?

A
  1. Skin
  2. Mucous membrane
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36
Q

What are the features of the epidermis ?

A
  1. Multiple layers of cells
  2. Lipid rich - therefore a tight water barrier
  3. Glands which produce anti microbial molecules and patrolling immune cells
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37
Q

What are the features of the mucosal surface ?

A
  1. One cell layer thick
  2. Covered with mucus and often cilia
  3. Significant immune cell infiltrate beneath
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38
Q

What do tight junction proteins do ?

A

Maintain epithelial integrity

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39
Q

What is included in tight junction proteins ?

A
  1. Claudins
  2. Occludins
  3. JAMs
  4. Tricellulins
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40
Q

What do pathogens target for invasion ?

A

Tight junction proteins

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41
Q

What are the mechanical barriers to infection ?

A
  1. Skin
  2. Gut
  3. Lungs
  4. Eyes/nose/oral cavity
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42
Q

What are the chemical barriers to infection ?

A
  1. Lysozymes in tears
  2. Mucus lining in trachea
  3. Rapid pH cchange in gut
  4. Flushing of urinary tract
  5. Intact skin, fatty acids, commensals
  6. Digestive enzymes
  7. Vaginal acids
43
Q

What is lysozymes specific to ?

A

Bacteria only

44
Q

What does lysozyme do ?

A

Host enzyme targets bacterial cell wall

45
Q

What type of bacteria is lysozyme more effective against ?

A

Gram positive bacteria

46
Q

What antimicrobial peptides are made by epithelial cells ?

A
  1. TH17
  2. IL17
47
Q

What do antimicrobial peptides made by epithelial cells act on ?

A

Mucosal fluid

48
Q

What do anti-microbial peptides cause ?

A

Target cell lysis

49
Q

What are the three evolutionary conserved families of anti-microbial peptides ?

A
  1. Defensins
  2. Cathelicidins
  3. Lecticidins
50
Q

What do anti-microbial pepides cause ?

A
  1. Pore formation
  2. Target cell lysis
51
Q

What do antimicrobial peptides have ?

A

A cationic portion and a hydrophobic core

52
Q

What do antimicrobial peptides repel ?

A

Eukaryotic membranes - neutral cationic

53
Q

What do anti-microbial peptides do ?

A

Insert into bacterial membranes which are anionic- hyrophobic

54
Q

What do commensals have ?

A

Many mutualistic relationships

55
Q

What is dysbiosis ?

A

Abnormal ratio of beneficial and agressive bacterial species

56
Q

What is a key characteristic of IBD ?

A

Dysbiosis

57
Q

What do commensal microbiota need to avoid ?

A

luminal expression of toll like receptors on epithelial cells for example mucin

58
Q

What is sensed and induced by commensal microbiota ?

A

A protective response example defensis

A tolerant response example regulatory T cells

59
Q

What are pre existing innate defences ?

A

Chemicals with anti microbial properties found in body in anticipation of infection

60
Q

What do pre existing innate defences not require ?

A

Induced inflammatory response to be made

61
Q

What is there some level of in pre existing innate defences ?

A

Pattern recognition

62
Q

What are some examples of anti-microbial enzymes ?

A
  1. Lysozymes
  2. Amylase
  3. Phospholipase A2
63
Q

What are some examples of anti-microbial peptides ?

A
  1. Defensins
    2.
64
Q

What are pre existing blood and tissues that require activation/pattern recognition for full anti-microbial function ?

A
  1. Complement
  2. Coagulation proteins
65
Q

What are the stages of complement action ?

A
  1. Pattern recognition trigger
  2. Protease cascade amplification/C3 convertase
  3. Inflammation
  4. Pagocytosis
  5. Membrane attack
66
Q

What is the complement system ?

A

Collection of soluble proteins found in blood and other bodily fluids

67
Q

Where is the complement system mainly synthesised ?

A
  1. liver
  2. Immune cells
68
Q

What happens once the complement system is activated ?

A

Important host defense and anti microbial function

69
Q

How does the complement system activate proteins ?

A

A cascade system of proteins through proteolytic cleavage

70
Q

What complex promotes cascasde (C1q) ?

A

AB-Ag complex

71
Q

What binds CHO on pathogen in complement ?

A

Mannose binding lectin or ficolins

72
Q

What is the alternative binding on a pathogen ?

A

C3 serum protein by spontaneous hydrolysis to C3b

73
Q

What do all complement pathways generate ?

A

A c3 convertase

74
Q

What does c3 convertase do ?

A

Cleaves C3 leaving C3b bound to the microbial surface and releasing C3a

75
Q

What does activation in the complement system lead to ?

A
  1. Phagocytosis of microbes
  2. Cell lysis
  3. Inflammation
76
Q

What are the effector pathways from C3 cleavage ?

A
  1. C3b
  2. C3a
77
Q

What does C3b do ?

A
  1. Binds pathogen or Ag:Ab complex
  2. Attaches to C3 receptor on phagocytic cells and induces phagocytosis
  3. Interacts with C5 complexes and forms membrane attack complex causing lysis
78
Q

What does C3a do ?

A
  1. Associates with c5a
  2. Promotes inflammation through binding to mast cells
  3. Promoting degranulation
  4. Vasodilation
  5. Activate mast cells
79
Q

What does C5b do ?

A

Binds C6 and C7

80
Q

What do c5b67 complexes do ?

A

Bind to membrane via C7

81
Q

What does c8 do ?

A

Binds to the C5b67 complex and inserts into the cell membrane

82
Q

What does c9 do ?

A

Bind to the complex and polymerise

83
Q

How does a pore form in the membrane ?

A

10-16 molecules of C9 bind to complex

84
Q

What does c3b have an affinity for ?

A

Microbial surfaces due to thioester bond

85
Q

What is the antibody recognised by ?

A

Fc receptor on phagocytes

86
Q

What is the complement c3b recognised by ?

A

CR1

87
Q

What are the cardinal features of inflammation ?

A
  1. Redness
  2. Pain
  3. Heat
  4. Swelling
  5. Loss of function
88
Q

How are the cardinal features alleviated ?

A

Vasculature and action of clotting proteins

89
Q

What is the route for recruitment of new immune cells ?

A

Blood vessels

90
Q

What do blood vessels do ?

A

Delivers proteins, complement, anti-microbial peptides and clotting factors

91
Q

What inflammatory mediators cause vasodilation ?

A
  1. Bradykinin C5a
  2. Histamine 5HT
  3. Nitric oxide
  4. Substance O
92
Q

Where is bradykinin found ?

A

Blood

93
Q

What is the specific function of bradykinin C5a ?

A

Protease cascade

94
Q

Where is histamine 5HT found ?

A

Mast cells and platlets

95
Q

What is the specific function of histamine 5HT ?

A

Degranulation

96
Q

Where is nitric oxide found ?

A

Endothelial cells

97
Q

What is nitric oxide induced by ?

A

Cytokines

98
Q

Where is substance P found ?

A

Neurons

99
Q

What is the clotting activation signal ?

A

Thrombin activation

100
Q

What is the clotting intrinsic pathway caused by ?

A

Vascular injury - contact clotting factors

101
Q

What is the extrinsic clotting pathway ?

A

Tissue damage - tissue factor

102
Q

When are clots degraded ?

A

When tissue repair occurs

103
Q

What promotes tissue repair ?

A

Fibrinolytic proteins (plasminogen)

Core Concepts in Immunology (22 decks)

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