Lecture 2. Inflammation and Innate Defences Flashcards
1
Q
What is the timeline of a primary immune response?
A
- Pre-formed/innate response
- Induced inflammatory response
- Specific adaptive response
2
Q
What does the induced inflammatory response rely on ?
A
Recognition of danger
3
Q
Why does the adaptive immune response occur late ?
A
Lymphocyets specific for the invading pathogen must first undergo clonal expansion
4
Q
Where are naive T-lymphocytes found ?
A
Lymph nodes
5
Q
What are the general PAMPs ?
A
- LPS
- dsRNA
- CpG
- DNA
6
Q
What are the two cell types involved in the innate immunity ?
A
- Macrophages
- Dendritic cells
7
Q
What are the pathogen recognition receptors ?
A
- TLRs
- CLRs
8
Q
What are some specific antigens involved in the adaptive immunity ?
A
- PHA
- Ovalbumin
9
Q
What are the cells involved in the adaptive immunity ?
A
- T cells
- B cells
10
Q
What does the innate immunity form ?
A
One of the earliest responses to infection
11
Q
What does the innate immune system do ?
A
Distinguish self from non-self
12
Q
What does the innate immune system activate ?
A
Adaptive immune syste - if pathogen bypasses innate host defences
13
Q
What function does the innate immunity carry out ?
A
A delaying function
14
Q
What is the delaying function of the innate immune system ?
A
Keeping pathogen numbers in check while adaptive immune system gears up
15
Q
What is the innate immune system mediated by ?
A
- Innate immune cells
- Soluble effector proteins
16
Q
What are the three things involved in the innate immunity ?
A
- Physio-chemical barriers
- Humoral components
- Cellular components
17
Q
What does the induced inflammatory response do ?
A
Delivers cells and plasma proteins to infection sites
18
Q
What is the insult of the induced inflammatory response ?
A
Infection or damage
19
Q
What are the resident cells of the induced inflammatory response ?
A
- Macrophages
- Dendritic cells
- Epithelial cells
20
Q
What are the messengers involved in the induced inflammatory response ?
A
- Cytokines - IL1, TNF
- Chemokines - CXCL8
- Prostaglandins
21
Q
What is an epithelial cell ?
A
Local cell
22
Q
What are cytokines ?
A
Driver of inflammation
23
Q
What are the recruited cells in the induced inflammatory response ?
A
- Monocytes - macrophages and dendritic cells
- Neutrophils
24
Q
What is the first thing found at the site of infection ?
A
Neutrophils
25
What is the second thing found at an infection site ?
Mononucletide
26
What does CsF1 determine ?
Difference in macrophage an mononucleoties
27
What do neutrophils do ?
Have a short life, degranulate, netosis and expel nucleus
28
What are the effector mechanisms involves in the induced inflammatory response ?
1. Immune signalling
2. Cytokine production
3. Phagocytosis
4. Antigen presentation
29
When does the induced inflammatory response have an adaptive response ?
In the presence of specific antigens
30
What happens as a result of effector mechanisms and addaptive responses ?
Resolution of inflammation
31
What are the routes of infection ?
1. Inhalation
2. Direct contact
3. Invasion
4. Ingestion
32
What is infection ?
The invasion and multiplication of a pathogen in a susceptible host
33
What is invasion facilitated by ?
1. Toxins
2. Factors encoded by pathogens or immunosupression
3. Susceptibility in the host
34
When does infectious disease manifest ?
When infection results in clinical pathology or tissue damage
35
What are the epithelial surfaces involved in barriers to infection ?
1. Skin
2. Mucous membrane
36
What are the features of the epidermis ?
1. Multiple layers of cells
2. Lipid rich - therefore a tight water barrier
3. Glands which produce anti microbial molecules and patrolling immune cells
37
What are the features of the mucosal surface ?
1. One cell layer thick
2. Covered with mucus and often cilia
3. Significant immune cell infiltrate beneath
38
What do tight junction proteins do ?
Maintain epithelial integrity
39
What is included in tight junction proteins ?
1. Claudins
2. Occludins
3. JAMs
4. Tricellulins
40
What do pathogens target for invasion ?
Tight junction proteins
41
What are the mechanical barriers to infection ?
1. Skin
2. Gut
3. Lungs
4. Eyes/nose/oral cavity
42
What are the chemical barriers to infection ?
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
What is lysozymes specific to ?
Bacteria only
44
What does lysozyme do ?
Host enzyme targets bacterial cell wall
45
What type of bacteria is lysozyme more effective against ?
Gram positive bacteria
46
What antimicrobial peptides are made by epithelial cells ?
1. TH17
2. IL17
47
What do antimicrobial peptides made by epithelial cells act on ?
Mucosal fluid
48
What do anti-microbial peptides cause ?
Target cell lysis
49
What are the three evolutionary conserved families of anti-microbial peptides ?
1. Defensins
2. Cathelicidins
3. Lecticidins
50
What do anti-microbial pepides cause ?
1. Pore formation
2. Target cell lysis
51
What do antimicrobial peptides have ?
A cationic portion and a hydrophobic core
52
What do antimicrobial peptides repel ?
Eukaryotic membranes - neutral cationic
53
What do anti-microbial peptides do ?
Insert into bacterial membranes which are anionic- hyrophobic
54
What do commensals have ?
Many mutualistic relationships
55
What is dysbiosis ?
Abnormal ratio of beneficial and agressive bacterial species
56
What is a key characteristic of IBD ?
Dysbiosis
57
What do commensal microbiota need to avoid ?
luminal expression of toll like receptors on epithelial cells for example mucin
58
What is sensed and induced by commensal microbiota ?
A protective response example defensis
A tolerant response example regulatory T cells
59
What are pre existing innate defences ?
Chemicals with anti microbial properties found in body in anticipation of infection
60
What do pre existing innate defences not require ?
Induced inflammatory response to be made
61
What is there some level of in pre existing innate defences ?
Pattern recognition
62
What are some examples of anti-microbial enzymes ?
1. Lysozymes
2. Amylase
3. Phospholipase A2
63
What are some examples of anti-microbial peptides ?
1. Defensins
2.
64
What are pre existing blood and tissues that require activation/pattern recognition for full anti-microbial function ?
1. Complement
2. Coagulation proteins
65
What are the stages of complement action ?
1. Pattern recognition trigger
2. Protease cascade amplification/C3 convertase
3. Inflammation
4. Pagocytosis
5. Membrane attack
66
What is the complement system ?
Collection of soluble proteins found in blood and other bodily fluids
67
Where is the complement system mainly synthesised ?
1. liver
2. Immune cells
68
What happens once the complement system is activated ?
Important host defense and anti microbial function
69
How does the complement system activate proteins ?
A cascade system of proteins through proteolytic cleavage
70
What complex promotes cascasde (C1q) ?
AB-Ag complex
71
What binds CHO on pathogen in complement ?
Mannose binding lectin or ficolins
72
What is the alternative binding on a pathogen ?
C3 serum protein by spontaneous hydrolysis to C3b
73
What do all complement pathways generate ?
A c3 convertase
74
What does c3 convertase do ?
Cleaves C3 leaving C3b bound to the microbial surface and releasing C3a
75
What does activation in the complement system lead to ?
1. Phagocytosis of microbes
2. Cell lysis
3. Inflammation
76
What are the effector pathways from C3 cleavage ?
1. C3b
2. C3a
77
What does C3b do ?
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
What does C3a do ?
1. Associates with c5a
2. Promotes inflammation through binding to mast cells
3. Promoting degranulation
4. Vasodilation
5. Activate mast cells
79
What does C5b do ?
Binds C6 and C7
80
What do c5b67 complexes do ?
Bind to membrane via C7
81
What does c8 do ?
Binds to the C5b67 complex and inserts into the cell membrane
82
What does c9 do ?
Bind to the complex and polymerise
83
How does a pore form in the membrane ?
10-16 molecules of C9 bind to complex
84
What does c3b have an affinity for ?
Microbial surfaces due to thioester bond
85
What is the antibody recognised by ?
Fc receptor on phagocytes
86
What is the complement c3b recognised by ?
CR1
87
What are the cardinal features of inflammation ?
1. Redness
2. Pain
3. Heat
4. Swelling
5. Loss of function
88
How are the cardinal features alleviated ?
Vasculature and action of clotting proteins
89
What is the route for recruitment of new immune cells ?
Blood vessels
90
What do blood vessels do ?
Delivers proteins, complement, anti-microbial peptides and clotting factors
91
What inflammatory mediators cause vasodilation ?
1. Bradykinin C5a
2. Histamine 5HT
3. Nitric oxide
4. Substance O
92
Where is bradykinin found ?
Blood
93
What is the specific function of bradykinin C5a ?
Protease cascade
94
Where is histamine 5HT found ?
Mast cells and platlets
95
What is the specific function of histamine 5HT ?
Degranulation
96
Where is nitric oxide found ?
Endothelial cells
97
What is nitric oxide induced by ?
Cytokines
98
Where is substance P found ?
Neurons
99
What is the clotting activation signal ?
Thrombin activation
100
What is the clotting intrinsic pathway caused by ?
Vascular injury - contact clotting factors
101
What is the extrinsic clotting pathway ?
Tissue damage - tissue factor
102
When are clots degraded ?
When tissue repair occurs
103
What promotes tissue repair ?
Fibrinolytic proteins (plasminogen)
