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Immunity and Disease > Lecture 11 and 12: Beneficial Interactions of Bacteria with the Host > Flashcards

Lecture 11 and 12: Beneficial Interactions of Bacteria with the Host Flashcards

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1
Q

What is the role of the microbiome ?

A

The microbiome influences multiple host functions that have a direct impact on human health

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2
Q

What is the metagenomic approach ?

A

Study of genetic material directly from environmental samples

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3
Q

What are most bacteria not ?

A

They are not culturable

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4
Q

What is the 16s RNA subunit used for ?

A

Studying the evolutionary relationship between species

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5
Q

How are phylogenetic relationships between bacteria established ?

A

By comparing the stable part of the genetic code

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6
Q

What is whole genome shotgun sequencing ?

A

DNA broken up into fragments which are then sequnced. Multiple overlapping reads generated which are then overlapped to assemble into a continuous sequence

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7
Q

What is the aim of the human microbiome project ?

A

Aims to characterise the microbial communities found at several sites i the body

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8
Q

What is symbiosis ?

A

Associations in which one organism lives on or inside the other

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9
Q

What is mutualistic ?

A

Relationship beneficial to both species

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10
Q

What is commensalistic ?

A

Relationship where one organism benefits while the other is unaffected

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11
Q

What is parasitic ?

A

Relationship where one organism benefits at the expense of the other

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12
Q

What is a pathobiont ?

A

Any commensal species that does not normally elicit an inflammatory response but under particular conditions has the potential to cause dysregulated inflammation and lead to disease

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13
Q

What is a pathogen ?

A

An infectious agent that can cause disease to its host

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14
Q

What is the microbiota ?

A

Microbial organisms that make up the microbiome

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15
Q

What is the microbiome ?

A

Collection of genomes from all microorganisms

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16
Q

What are the sterile body sites ?

A
  1. Solid organs
  2. Blood
  3. Cerebrospinal fluid
  4. Urine
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17
Q

What are the colonised body sites ?

A
  1. Skin
  2. Nasal passage
  3. Oral mucosa
  4. Intestinal mucosa
  5. Urogenital mucosa
  6. Respiratory tract
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18
Q

How many bacteria phyla are human microbiota dominated by ?

A

4

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19
Q

What is exclusivity ?

A

Specific type of interaction with hosts that faciltates colonisation of specific site

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20
Q

What represents the most significant microbiota ?

A

Gastrointestinal tract

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21
Q

What are functions of the intestinal microbiota ?

A
  1. Digesiton of food and provision of nutrients
  2. Protection against colonisation with pathogenic organisms
  3. Epithelial homeostasis, differentiation of mucosa, maintenance of barrier integrity
  4. “Education” of the immune system, establishing immune tolerance
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22
Q

When is the fetus sterile ?

A

In utero

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23
Q

When does colonisation of fetus begin and end ?

A

Begins immediately after birth and ends by one week

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24
Q

What is modulated throughout life ?

A

Composition of gut flora influenced by host and environmental factors in the first year of life

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25
What are early life factors that impact the development of the microbiota ?
1. Mode of delivery 2. Infant feeding 3. Hospitalisation and premature birth 4. Antibiotic use by mother during pregnancy and at time of delivery
26
What are life long factors that impact the development of mirobiota ?
1. Antibiotic use 2. Diet 3. Obesity 4. Use of probiotics
27
What do antibiotics affect ?
Gene expression, protein activity and overall metabolism of gut microbiota
28
What is clostridium difficile role ?
1. Toxins 2. Hydrolytic enzyme 3. Increases vascular permeability 4. Inflammation 5. Disrupt epithelial tight junctions
29
What is a treatment of clostridium difficile ?
Fecal transplantation
30
What is the hygiene hypothesis ?
The lack of exposure of microorganisms and parasites has led to increased incidents of asmtha, allergies and atopic disease
31
What organ has the largest surface area ?
GI tract
32
What is gut associated lymphoid tissue ?
Organised lymphoid tissue/immune inductive sites
33
What are the functions of gut associated lymphoid tissue ?
1. Sites of T cell education 2. Initiation of immune responses
34
What are the main gut associated lymphoi tissues ?
1. Peyers patches 2. Mesenteric lymphnodes
35
What are peyers patches ?
1. Large number of B cell follicles 2. Intervening T cell areas
36
What separates peyers patches from intestinal lumen ?
Layers of epithelial cell
37
What does the layer of epithelial cell in gut associated lymphoid tissue ?
Specialised M cells
38
What is the function of specialised m cells ?
Take up antigen from lumen
39
What is the sub-epithelial dome rich in ?
Dendritic cell, B cell and T cells
40
What are mesenteric lymphnodes connected by ?
Connected by lymphatics to peyers patch
41
What is the function of the mesenteric lymphnode ?
Site of further T cell maturation
42
What are scattered lymphoid tissue/immune effector sites ?
Sites of mature effector T cells and B cells (IgA producing plasma cells), lamina propria and intraepithelial lymphocytes
43
What are intraepithelial lymphocytes ?
Mainly lymphocytes, predominantly CD8
44
What are lamina propia ?
CD4 and CD8, dendritic cells, plasma cells and macrophages
45
How do T cells enter peyers patches ?
From blood vessels directed by the honing receptors CC47 and L-selectin
46
What do T cells in peyers patches encounter?
Antigens transported across M cells and become activated by dendritic cells
47
What do activated T cells drain via ?
Mesenteric lymph nodes to the thoracic duct
48
What hones to the lamina propia and intestinal epithelium of the small intestine ?
Activated T cell expressing Alpha4:Beta7 integrin and CCR9
49
What does gut honing effector T cells bind on the epithelium ?
MAdCAM-1
50
What is the dominant class of antibody at mucosal surface ?
IgA
51
What is IgA produced as ?
Dimers of IgA and secretory component
52
Where is IgA synthesised ?
Plasma cells lying beneath epithelial basement membranes of the gut
53
What is IgA bound by ?
Polymeric Ig receptor (plgR) expressed by epithelial cells
54
What does the IgA complex undergo ?
Transcytosis
55
What is cleaved from the IgA complex after transcytosis ?
plgR
56
What does the carbohydrate on the secretory component bind ?
Binds to mucins in mucus and holds the IgA at the epithelial surface
57
What does the carbohydrate on the secreting component binding mucins prevent ?
Adherence of bacteria and neutralises toxins
58
What do toxins that reach the lamina propia encounter ?
Antigen specific IgA in the lamina propia
59
What is the main function of IgA ?
To limit access of pathogens to mucosal surface without causing inflammation
60
What can IgA not activate ?
Complement or act as opsonisation
61
What is class switching of IgA under the control of ?
TGF-Beta
62
What is immune tolerance ?
Process by which immune system does not respond to antigens
63
What does tolerance involve ?
1. Deletion of antigen-specific T cells 2. Generation of regulatory T cells
64
What does intestinal epithelium create ?
Essential barrier to microbiota
65
What do commensals not invade ?
Epithelium
66
What are some barriers to microbiota ?
1. IEC tight junctions 2. Microvilli 3. Goblet cells producing mucous 4. Secreted IgA
67
What is there low expression of on the apical surface of the intestinal epithelium ?
TLR
68
What is there increased expression of on the intestinal epithelium ?
Inhibitor molecules
69
Where is TLR5 expressed ?
On basolateral surface
70
What are intracellular pathogen recognition receptors ?
TLRP, NOD1, NOD2
71
What are gnotobiotic mice ?
Germ free mice - lack a microbiota and have an underdeveloped immune system
72
What are the defects in the gut associated lymphoid tissue of germ free mice ?
1. Fewer peyers patches 2. Smaller less ceullurlar mesenteric lymph node 3. Less cellular lamina propia
73
What is there reduced of in germ free mice ?
1, Reduced IEL 2. Reduced expression of TLR and MHCII on intestinal epithelium 3. Reduced IgA secretion 4. Reduced CD4+ and B cells in spleen
74
What is the cell surface marker CD103+ expressed by ?
Dendritic cells from lamina propia also mesenteric lymph nodes but only a small proportion of splenic dendritic cells
75
What do dendritic cells from the peyers patch and lamina propia produce ?
High levels of anti-inflammatory cytokines TGF-B and IL10
76
What do splenic dendritic cells produce ?
pro-inflammatory cytokines IL12
77
What does the expression of CD103+ induce ?
1. IgA secretions by naive B cells in mesenteric lymph nodes which then migrate to lamina propia as IgA secreting plasama cells 2. Induce expression of gut honing receptors on activated B and T cells 3. Drives differentiation of FoxP3+ T reg cells
78
What are the conditioning signals produced by intestinal epithelial cells ?
1. TGF-B 2. Thymic stromal lymphopoietin acts on dendritic cells to downregulate IL12 and drive IL10/TGF-B 3. Vitamin A metablosied by dendritic cells to retonic acid
79
What do T reg cells suppress ?
Effector T cell responses
80
What are the two types of T reg cells ?
1. Naturally occuring 2. Inducible
81
What is the major site for postnatal maturation of T cells ?
Interaction with microbes in GI tract
82
What are newly born babies skewed for at birth ?
Th2
83
What stimulates Th1 cell expansion ?
Exposure to microbial antigens
84
Why is Th1/Th2 balance important ?
Protection against allergic disease
85
What are the impacts of intestinal microbiota on T cells ?
1. Promote Th1 cells in the periphery which ensures TH1/TH2 balance 2. Drives regulatory T cells in gut 3. Drives Th17 in gut

Immunity and Disease (2 decks)

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