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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

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
Q

What are early life factors that impact the development of the microbiota ?

A
  1. Mode of delivery
  2. Infant feeding
  3. Hospitalisation and premature birth
  4. Antibiotic use by mother during pregnancy and at time of delivery
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26
Q

What are life long factors that impact the development of mirobiota ?

A
  1. Antibiotic use
  2. Diet
  3. Obesity
  4. Use of probiotics
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27
Q

What do antibiotics affect ?

A

Gene expression, protein activity and overall metabolism of gut microbiota

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28
Q

What is clostridium difficile role ?

A
  1. Toxins
  2. Hydrolytic enzyme
  3. Increases vascular permeability
  4. Inflammation
  5. Disrupt epithelial tight junctions
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29
Q

What is a treatment of clostridium difficile ?

A

Fecal transplantation

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30
Q

What is the hygiene hypothesis ?

A

The lack of exposure of microorganisms and parasites has led to increased incidents of asmtha, allergies and atopic disease

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31
Q

What organ has the largest surface area ?

A

GI tract

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32
Q

What is gut associated lymphoid tissue ?

A

Organised lymphoid tissue/immune inductive sites

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33
Q

What are the functions of gut associated lymphoid tissue ?

A
  1. Sites of T cell education
  2. Initiation of immune responses
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34
Q

What are the main gut associated lymphoi tissues ?

A
  1. Peyers patches
  2. Mesenteric lymphnodes
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35
Q

What are peyers patches ?

A
  1. Large number of B cell follicles
  2. Intervening T cell areas
36
Q

What separates peyers patches from intestinal lumen ?

A

Layers of epithelial cell

37
Q

What does the layer of epithelial cell in gut associated lymphoid tissue ?

A

Specialised M cells

38
Q

What is the function of specialised m cells ?

A

Take up antigen from lumen

39
Q

What is the sub-epithelial dome rich in ?

A

Dendritic cell, B cell and T cells

40
Q

What are mesenteric lymphnodes connected by ?

A

Connected by lymphatics to peyers patch

41
Q

What is the function of the mesenteric lymphnode ?

A

Site of further T cell maturation

42
Q

What are scattered lymphoid tissue/immune effector sites ?

A

Sites of mature effector T cells and B cells (IgA producing plasma cells), lamina propria and intraepithelial lymphocytes

43
Q

What are intraepithelial lymphocytes ?

A

Mainly lymphocytes, predominantly CD8

44
Q

What are lamina propia ?

A

CD4 and CD8, dendritic cells, plasma cells and macrophages

45
Q

How do T cells enter peyers patches ?

A

From blood vessels directed by the honing receptors CC47 and L-selectin

46
Q

What do T cells in peyers patches encounter?

A

Antigens transported across M cells and become activated by dendritic cells

47
Q

What do activated T cells drain via ?

A

Mesenteric lymph nodes to the thoracic duct

48
Q

What hones to the lamina propia and intestinal epithelium of the small intestine ?

A

Activated T cell expressing Alpha4:Beta7 integrin and CCR9

49
Q

What does gut honing effector T cells bind on the epithelium ?

A

MAdCAM-1

50
Q

What is the dominant class of antibody at mucosal surface ?

A

IgA

51
Q

What is IgA produced as ?

A

Dimers of IgA and secretory component

52
Q

Where is IgA synthesised ?

A

Plasma cells lying beneath epithelial basement membranes of the gut

53
Q

What is IgA bound by ?

A

Polymeric Ig receptor (plgR) expressed by epithelial cells

54
Q

What does the IgA complex undergo ?

A

Transcytosis

55
Q

What is cleaved from the IgA complex after transcytosis ?

A

plgR

56
Q

What does the carbohydrate on the secretory component bind ?

A

Binds to mucins in mucus and holds the IgA at the epithelial surface

57
Q

What does the carbohydrate on the secreting component binding mucins prevent ?

A

Adherence of bacteria and neutralises toxins

58
Q

What do toxins that reach the lamina propia encounter ?

A

Antigen specific IgA in the lamina propia

59
Q

What is the main function of IgA ?

A

To limit access of pathogens to mucosal surface without causing inflammation

60
Q

What can IgA not activate ?

A

Complement or act as opsonisation

61
Q

What is class switching of IgA under the control of ?

A

TGF-Beta

62
Q

What is immune tolerance ?

A

Process by which immune system does not respond to antigens

63
Q

What does tolerance involve ?

A
  1. Deletion of antigen-specific T cells
  2. Generation of regulatory T cells
64
Q

What does intestinal epithelium create ?

A

Essential barrier to microbiota

65
Q

What do commensals not invade ?

A

Epithelium

66
Q

What are some barriers to microbiota ?

A
  1. IEC tight junctions
  2. Microvilli
  3. Goblet cells producing mucous
  4. Secreted IgA
67
Q

What is there low expression of on the apical surface of the intestinal epithelium ?

A

TLR

68
Q

What is there increased expression of on the intestinal epithelium ?

A

Inhibitor molecules

69
Q

Where is TLR5 expressed ?

A

On basolateral surface

70
Q

What are intracellular pathogen recognition receptors ?

A

TLRP, NOD1, NOD2

71
Q

What are gnotobiotic mice ?

A

Germ free mice - lack a microbiota and have an underdeveloped immune system

72
Q

What are the defects in the gut associated lymphoid tissue of germ free mice ?

A
  1. Fewer peyers patches
  2. Smaller less ceullurlar mesenteric lymph node
  3. Less cellular lamina propia
73
Q

What is there reduced of in germ free mice ?

A

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
Q

What is the cell surface marker CD103+ expressed by ?

A

Dendritic cells from lamina propia also mesenteric lymph nodes but only a small proportion of splenic dendritic cells

75
Q

What do dendritic cells from the peyers patch and lamina propia produce ?

A

High levels of anti-inflammatory cytokines TGF-B and IL10

76
Q

What do splenic dendritic cells produce ?

A

pro-inflammatory cytokines IL12

77
Q

What does the expression of CD103+ induce ?

A
  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
Q

What are the conditioning signals produced by intestinal epithelial cells ?

A
  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
Q

What do T reg cells suppress ?

A

Effector T cell responses

80
Q

What are the two types of T reg cells ?

A
  1. Naturally occuring
  2. Inducible
81
Q

What is the major site for postnatal maturation of T cells ?

A

Interaction with microbes in GI tract

82
Q

What are newly born babies skewed for at birth ?

A

Th2

83
Q

What stimulates Th1 cell expansion ?

A

Exposure to microbial antigens

84
Q

Why is Th1/Th2 balance important ?

A

Protection against allergic disease

85
Q

What are the impacts of intestinal microbiota on T cells ?

A
  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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