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BS - Gastrointestinal System pt.1 > GI Immunity > Flashcards

GI Immunity Flashcards

1
Q

What are the components of the innate immune system in the GI tract?

A
  1. barrier and chemical mechanisms
  2. pattern recognition receptors (PRRs)
  3. cellular (phagocytes, NK cells)
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2
Q

How do the innate and adaptive immune systems communicate in the GI tract?

A

There is a high degree of communication and overlap between the 2 systems

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3
Q

What are pattern recognition receptors (PRRs)?

A

They are proteins expressed by macrophages, neutrophils and epithelial cells

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4
Q

What do PRRs detect?

A

They detect molecules that are typical for a particular type of pathogen

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5
Q

What are the 2 types of molecules that are detected by PRRs?

A

Pathogen-associated molecular patterns (PAMPs)

Damage-associated molecular patterns (DAMPs)

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6
Q

What are PAMPs and DAMPs associated with?

A

PAMPs are associated with microbial pathogens

DAMPs are associated with components of host cells that are released during cell damage/death

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7
Q

Where may PRRs be found within a cell?

A

They are either transmembrane (on cell surface)

or they are found intracellularly

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8
Q

What are examples of PRRs?

A
  1. Toll-like receptors
  2. NOD-like receptors
  3. Rigi-like receptors
  4. C-type lectins
  5. Scavenger receptors
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9
Q

What are the targets for antimicrobial peptides?

A

The fundamental differences between prokaryotic and eukaryotic cells

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10
Q

What type of organisms are killed by antimicrobial peptides?

A

Gram-negative and Gram-positive bacteria

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11
Q

What are examples of antimicrobial peptides?

A
  1. defensins
  2. probiotics
  3. granulysin
  4. histatin
  5. cathelin
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12
Q

What are the 5 main components of the GI innate immune system?

A
  1. pattern recognition receptors
  2. antimicrobial peptides
  3. cells
  4. complement components
  5. cytokines
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13
Q

What types of cytokines are produced and what is their main role?

A

Autocrine, paracrine and endocrine cytokines mediate host defence and inflammation

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14
Q

What is the role of cytokines, relating to the adaptive immune response?

A

They recruit, direct and regulate adaptive immune responses

This involves communication between different components of the immune system

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15
Q

What is the role of macrophages in the innate immune response?

A
  1. phagocytose and kill bacteria
  2. produce antimicrobial peptides
  3. produce inflammatory cytokines
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16
Q

What do macrophages in the innate immune system bind?

A

They bind lipopolysaccharides (LPS)

These are found in the outer membrane of Gram-negative bacteria

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17
Q

Where are plasmacytoid dendritic cells found?

A

In T cell zones of lymphoid organs and will circulate in the blood

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18
Q

What is the role of plasmacytoid dendritic cells?

A

They produce large amounts of interferon

This has anti-tumour and anti-viral activity

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19
Q

Where are myeloid dendritic cells found?

A

In T cell zones of lymphoid organs and will circulate in the blood

They are present in the interstices of the lung, heart and kidney

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20
Q

What is the role of myeloid dendritic cells?

A

They produce IL-12 and IL-10

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21
Q

What is the role of natural killer cells?

A

They kill foreign and host cells that have low levels of MHC-positive self-peptides

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22
Q

What is the role of NK-receptors on NK cells?

A

They can inhibit NK function in the presence of high expression of self-MHC

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23
Q

What are NK-T cells?

A

Lymphocytes which have both T cell and NK cell surface markers

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24
Q

what is the role of NK-T cells?

A

They recognise lipid antigens of intracellular bacteria through CD1 molecules

They then kill host cells infected by intracellular bacteria

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25
Q

What is the role of neutrophils in the innate immune system?

A
  1. phagocytose and kill bacteria

2. produce antimicrobial peptides

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26
Q

What is the role of eosinophils in the innate immune response?

A

They kill invading parasites

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27
Q

What is the role of mast cells and basophils in the innate immune response?

A

They release TNF, IL-6 and IFN in response to a variety of bacterial PAMPs

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28
Q

What is the role of epithelial cells in the innate immune response?

A
  1. produce antimicrobial peptides

2. tissue-specific epithelia produce mediators of local innate immunity

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29
Q

What is significant about the adaptive immune system being able to evolve?

A

It evolves in response to changing pathogen structures

Variable regions of pathogens mutate at a greater speed than humans

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30
Q

What is significant about the antigen receptor found on each lymphocyte?

A

It is unique to a particular pathogen

infection by the specific antigen leads to clonal expansion of the lymphocyte

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31
Q

What actions precede antigen presentation?

A
  1. antigens are internalised and broken down into peptides
  2. peptides associate with newly synthesises MHC II molecules
  3. peptides and MHC II molecules are brought to the cell surface
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32
Q

What happens if the presented peptides are foreign?

A

They are recognised by helper T cells

The helper T cells then produce cytokines to activate B cells and other T cells

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33
Q

When the T helper cell activates the B cell, which groups of molecules interact?

A

CD40L on the T helper cell interact with CD40 on the B cell

IL2, IL4 and IL5 are released by the T cell and detected by the interleukin receptor in the B cell

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34
Q

What do CD4+ helper T cells recognise?

A

Exogenous antigens presented by MHC II molecules

MHC II are on the surface of APCs - B cells, dendritic cells and macrophages

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35
Q

What do CD8+ cytotoxic T cells recognise?

A

Endogenous antigens presented by MHC I molecules

MHC I is present on the surface of ALL nucleated cells (platelets but not RBCs)

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36
Q

What are Th1 cells involved in?

A

Defence against intracellular pathogens

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37
Q

What are Th2 cells involved in?

A

Defence against parasitic worms, as well as allergy and asthma

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38
Q

What are Th17 cells involved in?

A

Defence against extracellular bacteria

Also have a role in autoimmunity and cancer

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39
Q

What are Treg cells involved in?

A

Immunosuppression

This is dampening down the immune response

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40
Q

Why is it important that the gut has a well developed immune system?

A

The gut is the major site of contact in the body for foreign antigens

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41
Q

What is the first line of defence against pathogens in the gut?

A

The GI tract mucosal surface

This separates the external environment from the internal sterile environment

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42
Q

What 3 categories of antigens does the gut mucosal barrier encounter?

A
  1. harmless antigens e.g. in food
  2. commensal bacterial flora
  3. pathogenic organisms that have developed effective methods for colonisation and invasion
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43
Q

What is the difference in immune response required for harmless antigens and pathogenic antigens?

A

Harmless antigens require active suppression through the development of tolerance

Pathogenic organisms require a protective immune response

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44
Q

Why is the gut immune system functionally and anatomically different from the systemic IS?

Why is this significant?

A

The gut immune system is capable of mounting a robust response against pathogenic antigens

It also is capable of maintaining a required tolerance against non-pathogenic antigens

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45
Q

What are the 3 main components of the gut immune system?

A
  1. innate defences
  2. specific defences
  3. microfold cells
46
Q

What are the main innate defences of the gut immune system?

A
  1. commensal bacterial flora
  2. epithelial barriers
  3. biochemical factors produced by epithelial cells
47
Q

What are the main specific defences of the gut immune system?

A

Lymphoid tissue associated with mucosal surfaces

This is gut-associated lymphoid tissue - GALT

48
Q

Where are microfold (M cells) located?

A

Within Peyer’s patches

49
Q

What is the role of the microfold (M) cells?

A

They sample antigen from the lumen of the small intestine and deliver it to antigen-presenting cells and lymphocytes via transcytosis

50
Q

Where are the M cells located with respect to the antigen-presenting cells and lymphocytes?

A

The M cells are in the Peyer’s patches touching the gut lumen

The lymphocytes and APCs are located in a pocket-like structure on the basolateral side

51
Q

How do M cells differ from enterocytes?

A

They lack microvilli on their apical surface

Instead, they have broader microfolds

They are also less abundant than enterocytes

52
Q

What are enterocytes?

A

Simple columnar epithelial cells found in the small intestine

53
Q

Approximately how many, and how many species of, bacteria live in the GI tract?

A

10^14 bacteria

There are 300 - 1000 species of bacteria in the gut, but most are commensals

54
Q

How may some of the bacteria in the gut be capable of causing harm?

A

Some are capable of causing disease through infection or increasing risk of cancer

55
Q

What is the optimum “gut flora balance”?

A

The beneficial bacteria should predominate and provide a barrier to invading organisms

56
Q

What are the most common ‘beneficial’ gut bacteria?

A

Gram-positive lactobacilli

Bifidobacteria

57
Q

How does the composition of GI flora vary?

A

It differs among individuals

It also differs during life within the same individual

58
Q

What are factors that can upset the balance of GI flora?

A
  1. climate
  2. increased age
  3. medication - especially antibiotics
  4. illness and stress
  5. infection
  6. socioeconomic circumstances and lifestyle
59
Q

How does intestinal bacterial composition change upon birth?

A

Foetuses are sterile in the womb

From birth, infants are exposed to microbes that originate from the mother and the surrounding environment

60
Q

Why does an infant’s gut flora closely mimic the mother’s gut flora?

A

the infant tends to acquire flora swallowed from vaginal fluid at birth

Vaginal flora and intestinal flora are similar

61
Q

At what age is colonic microflora considered adult-like?

A

2 years

62
Q

What happens to the bacterial groups in the faeces after the climax microflora has been reached?

A

The major bacterial groups in the faeces of adults remain relatively constant over time

63
Q

How do the types of bacteria in the elderly vary to younger adults?

A

The elderly harbour fewer bifidobacteria

They have higher levels of enterobacteria and Clostridium difficile

64
Q

What a prebiotic and what is its role?

A

It is a non-digestible food ingredient

It will encourage a specific type of bacteria to grow over another

65
Q

Why is a prebiotic beneficial to the host?

A

It selectively stimulates the growth and/or activity of one or a limited number of bacteria in the colon

This improves health

66
Q

What must happen to the prebiotic before it can perform its role?

A

It is fermented by microflora colonising the GI tract in the large bowel

67
Q

Where are prebiotics found?

A

Found naturally in breast milk and some foods (e.g. onions and bananas)

68
Q

What is the pathway that leads from breast milk to the maturation of the mucosal immune system?

A
  1. breast milk
  2. inulin-type fructans (prebiotic)
  3. colonic fermentation
  4. acidic pH
  5. lactobacillus, bifidobacteria (probiotics)
  6. stimulation of intestinal host defences
  7. maturation of mucosal immune system
69
Q

why does inulin pass through most of the digestive tract intact?

What happens to it in the colon?

A

It is indigestible by ptyalin and amylase (which digest starch)

In the colon it is fermented to release carbon dioxide, hydrogen and/or methane

70
Q

what are probiotics?

A

dietary supplements containing potentially beneficial bacteria or yeasts

71
Q

What are the 2 most common probiotic bacteria?

A

Lactobacillus and bifidobacteria

They are lactic acid producing Gram-positive bacteria

72
Q

Why do people take probiotics?

A

Normal intestinal microflora play a role in enhancing resistance to colonisation by exogenous, potentially pathogenic organisms

73
Q

What are the 6 main benefits of gut microflora?

A
  1. resistance to colonisation by pathogens
  2. stimulation of local immunity
  3. oral tolerance
  4. nutrition
  5. epithelial cell turnover
  6. intestinal motility
74
Q

What is symbiosis?

A

The development of a poor immune response in the absence of commensals

Oral tolerance cannot be induced

75
Q

What is meant by ‘nutrition’ being an essential benefit of gut microflora?

A

Intestinal flora has a high rate of metabolic activity

They complete for nutrients that are vital to the survival of pathogens

76
Q

What is the problem with antibiotics and commensal bacteria?

A

Antibiotics cause massive death of commensal bacteria in the colon

This allows pathogenic bacteria to proliferate and colonise the colon

77
Q

How do the commensal bacteria usually act as a physical barrier to prevent colonisation of pathogens?

A

The pathogens must be able to attach themselves to enterocytes before they can cause an infection

78
Q

What % of intestinal microflora are potentially pathogenic?

What conditions are commonly caused by gut microflora?

A

15%

Irritable bowel syndrome and ulcers

Ulcers are caused by Helicobacter pylori

79
Q

What is eubiosis?

A

A state of balance within the microbial population in the GI tract

80
Q

what is dysbiosis?

A

A state of imbalance within the microbial population of the GI tract

The greater the imbalance, the greater the symptoms of GI tract disease

81
Q

What extraintestinal diseases can be caused by gut microflora?

A
  1. septicaemia
  2. autoimmunity
  3. reactive arthritis
  4. allergy
82
Q

What is the purpose of the intestinal mucosal barrier?

A

It is a single layer of cells that prevents penetration by microorganisms

83
Q

What is meant by the epithelial barrier being a “self-renewing system”?

A

It undergoes continuous renewal from stem cells located near the base of the crypts of Lieberkhun

84
Q

What will stem cells at the base of the crypts of Lieberkhun differentiate into?

A
  1. enterocytes
  2. goblet cells
  3. enteroendocrine cells
  4. paneth cells
85
Q

what is the role of goblet cells?

A

They produce mucins to provide for mucous layers that resist microbial access

86
Q

what are the roles of the mucus layer?

A
  1. it traps pathogens and the cilia waft them away

2. it prevents excessive proliferation of healthy bacteria

87
Q

How do enterocytes remove pathogens?

A

They have cilial action that creates a current to remove microbes that are poorly adhered

88
Q

What antimicrobial chemicals are produced by enterocytes?

A
  1. antimicrobial peptides
  2. lysozyme
  3. lactoferrin
  4. defensins
  5. cathelicidins
89
Q

What is the problem with secretory IgA as a defence mechanism of the epithelial barrier?

A

It is of limited specificity to bind to microbes

90
Q

What is ‘organised mucosal-associated lymphoid tissue’?

What is its role?

A

It is known as mucosal follicles

They are involved in the induction of immune responses (specific defence)

91
Q

Where are mucosal follicles found?

A
  1. there are single follicles present along the length of the GI tract
  2. most follicles are aggregated in Peyer’s patches in the lower part of the SI and appendix
92
Q

What are Peyer’s patches?

A

They act as the lymph nodes of the gut

93
Q

What are ‘diffuse mucosal-associated comprising widespread lymphocytes’?

A

Intraepithelial lymphocytes that are interspersed between epithelial cells

Most of them are T cells (90%)

94
Q

What is the role of leucocytes in the lamina propria?

A

They act as effector sites for immune responses

This includes lymphocytes, macrophages, mast cells and neutrophils

95
Q

Within the GALT, what cells are found within Peyer’s patches?

A
  1. M cells
  2. antigen-presenting cells
  3. follicles containing B and T lymphocytes
96
Q

Why are Peyer’s patches open to the gut environment?

A

It allows them to recognise any pathogens which may be present

M cells on the surface provide continuous surveillance

97
Q

What is the first stage in induction of a specific immune response through a Peyer’s patch?

A

M cells take up antigens from the gut lumen

They pass the antigens to dendritic cells (APCs)

Dendritic cells present the antigen to T-cells

98
Q

What happens after the dendritic cells have presented the antigen to the T cells?

A

The T-cells activate B cells

B cells migrate to mesenteric lymph nodes and differentiate into plasma cells

Plasma cells in the tissues secrete IgA

99
Q

Where does T-cell priming occur?

A

In the mesenteric lymph nodes (MLNs)

100
Q

How are T-cells involved in the induction of tolerance?

A

They induce tolerance by active suppression/clonal anergy

101
Q

what are the 2 types of intestinal lymphocytes?

A
  1. intraepithelial lymphocytes (IEL)

2. lamina propria lymphocytes (LPL)

102
Q

Where are intraepithelial lymphocytes located?

What do they mostly consist of?

A

Located between intestinal epithelial cells

Consist mainly of CD8+ cytotoxic T cells

103
Q

What do intraepithelial lymphocytes produce?

A
  1. IL-2
  2. IFN gamma
  3. CCL5 (chemokine)
  4. perforin and granzyme
104
Q

what are the functions of intraepithelial lymphocytes?

A
  1. epithelial homeostasis
  2. mucosal barrier function
  3. reactivity with stress-induced epithelial cell antigens
105
Q

Where are lamina propria lymphocytes located?

What do they mostly consist of?

A

In the loose connective tissue that lies under the epithelium

Consist mainly of CD4+ helper T cells

106
Q

what are the functions of the lamina propria lymphocytes?

A
  1. Th1 cells provides defence against intracellular pathogens
  2. Th2 provide antibody-mediated response to allergens and parasites
  3. Th17 cells provide defence against mucosal pathogens
107
Q

Where is IgA synthesised?

Where is it transported to?

A

Synthesised by plasma cells in the lamina propria

Transported across the epithelium to be secreted in colostrum, maternal milk, salvia and tears

108
Q

What is the role of IgA?

A

Ir prevents attachment of bacteria or toxins to the epithelia

109
Q

What are the other functions of IgA?

A
  1. neutralises viruses and toxins

2. enhances non-specific defence mechanisms through lactoperoxidase and lactoferrin

110
Q

What is a main property of IgA?

A

It is relatively resistant to proteolysis

111
Q

What does IgA inhibit?

A
  1. bacterial adhesion
  2. macromolecule absorption
  3. inflammatory effects of other antibodies

BS - Gastrointestinal System pt.1 (22 decks)

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