Immunological features of the alimentary tract Flashcards

1
Q

the mouth is what?

A

a major portal for infection

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2
Q

what are located at the top of the throat?

A

Tonsils and adenoids

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3
Q

how can we split the immune system up?

A

innate vs adaptive

mucosal vs systemic

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4
Q

innate immune system

A

prevents you getting ill in the first place

prevents infection and avoids disease

non-specific

no memory

mediated by: macrophages, epithelial barriers, secretions…

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5
Q

adaptive immune system

A

responds to infection and prevents disease

highly specific response to targeted microbe

memory - allow quicker and more powerful response

mediated by:
Lymphocytes, antibodies

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6
Q

how might the bacteria end up in the faeces?

A

peristaltic waves push the bacteria

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7
Q

systemic immunity

A

bone marrow, spleen, thymus lymph system, blood circulation

part that actually responds to an injected vaccine, or a pathogen that has already breached the first epithelial barrier

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8
Q

mucosal immunity

A

protects all the wet parts of the body, external parts of the body covered in mucus membranes - oral, nasal, bronchial tract, lacrimal surfaces, eyes, gut, GI tract, genitourinary tract.

all the mucosal membranes are colonized by bacteria, most of them by good bacteria

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9
Q

the mucosal surfaces are what?

A

main route of entry for infectious microorganisms

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10
Q

although the gut has a large SA for absorption, why might this be a problem?

A

increases the surface area a microbe infecting it

so, it’s important we have a mucosal immune system specifically for protecting those mucosal surfaces

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11
Q

innate and adaptive mechanisms of the mucosal immune system

A

Innate mechanisms of protection include:

mucin, peristalsis, antimicrobial peptides and proteins e.g. lysozyme, lactoferrin; phagocytes

Adaptive mechanisms:

mucosal/secretory immune system

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12
Q

what is saliva made up of?

A

80% water
19% mucus - mucus is what makes it slippery
1% enzymes
also antibodies

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13
Q

lysozyme

A

breaks down bacteria phagocytes

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14
Q

lactoferrin

A

hoards iron to stop bacterial growth

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15
Q

phagocytes

A

engulf microbes

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16
Q

the mucosal immune system must do what?

A

discriminate between harmful pathogens and harmless antigens – foods and commensal bacteria

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17
Q

what happens when the process of distinguishing between good and bad bacteria breaks down?

A

develop food allergies

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18
Q

name some mucosal barriers

A

innate (natural barriers, eg. stomach)

  • Mucin
  • Peristalsis
  • Proteolysis
  • Microvillus membrane

immunological

  • Secretory IgA/IgM
  • IgG
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19
Q

gingival tissues

A

have an exudate going on the surface of the gums – serum exudate from the blood system

gingival fluid contains all the blood components except for RBCs (so antibodies, WBCs and phagocytes)

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20
Q

explain the contribution of the systemic immunity from the blood circulation into the mouth

A

all the solution in the mouth is predominantly from saliva

but, in the mouth you have a hard tissue that has its origins in the systemic system, and it breaks the epithelial layer to come into the mucosal layer

the junction where the tooth comes through the gum is a site of leakiness

all the blood vessels in this area are high pressure, exudate comes out - in this exudate you can find antibodies and white blood cells that have originated from blood

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21
Q

IGA deficiency

A

the mucosal immune system doesn’t work properly, and the exudate they get through the epithelial layer from the blood seems to increase

this is because the body recognises they don’t have mucosal immunity and compensates by increasing systemic immunity- so, they don’t get so many infections.

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22
Q

cel layers of the gut

A

the gut is lined by a single layer of columnar epithelial cells (important because you don’t want to food to have to get through multiple thick layers- adaptation)

the cells are ciliated which moves along the mucus and bacteria

underneath the epithelial layer is submucosa, and once you past this layer you can access the lymph nodes and blood vessels.

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23
Q

how can a bug in the lumen of the gut past these barriers and cause infection (i.e. into the bloodstream)?

A
  1. Breach of the epithelial layer (gastric/duodenal ulcer/inflammatory disease like Chrone’s)
  2. Attaching to dendritic cells (professional APC’s) but not getting engulfed, and then when the dendritic cell decides to come back in the virus is bought through the epithelial barrier in tact
  3. Some pathogens squeeze across between the epithelial junctions
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24
Q

what is not covered by normal epithelium?

A

Peyers patch - specialised cells in between the epithelial cells called M cells. When a pathogen gets across the epithelial barrier, WBC’s are waiting for the infecting organism.

25
peyers patches sample what?
M cells in the peyers patch sample what’s in the gut – look for what shouldn’t be there
26
Peyer’s Patches
Covered in a single layer of columnar epithelial dome, underneath the patch is lots and lots of WBC's
27
what is the peyers patch important in?
recognising the vaccine, initiating mucosal immune response
28
M cells
M stands for microfold - cells that are constantly sampling the gut lumen, seeing what’s in the gut Detects the pathogen and passes it onto the WBCs below White blood cells have pushed up inside the M cell (eg. is the M cells was a balloon, and the WBC’s were your fist)
29
how is the pathogen taken up by the WBC so quickly after it crosses the first barrier?
because the gap between the external surface of the gut and the first lymphocyte encountered by the WBC is very small
30
why might pathogens target M cells as their route of entry?
because the M cells are constantly sampling (active), and it will pick up nanoparticles (like viruses)
31
name a virus that specifically targets the M cells
Polio the virus will specifically bind to the M cell - the virus as actually labelled it as a point of weakness in our gut by targeting the M cell it can then enter our body if it evades the WBC’s underneath
32
migration of immune cells from Peyer’s Patches
Pathogen presented to a WBC- WBC’s are activated and start to move away from the Peyer’s patch, migrate through the mesenteric lymph node (lymph node inside the gut). They stay here and mature/develop a bit further before migrating to the blood system although the WBC’s get into the blood and circulate, as soon as they hit a mucosal tissue (eyes, mouth, breast, lungs) they will stay there and produce antibodies 10-15 days after a pathogens first encounter with the gut is that you seed all of your mucosal system with WBC’s which will produce antibodies
33
Introducing pathogen in the gut will enable you to see what?
a response in all the other mucosal sites
34
Common mucosal immune system
common because there is an interlinkedness between the immune response and where you see the immunity
35
Mucosal Antibodies
- Predominantly SIgA - Found in all secretions and breast milk (sterile) - Provide passive immune protection in new-born infants - traditional treatment for conjunctivitis
36
what are antibodies?
soluble proteins present in mucosal secretions
37
in the blood what antibody do we predominantly produce?
IgG antibodies
38
why are less IgG antibodies produced in the gut?
because they are very prone to being degraded- when this antibody gets into the gut proteolytic enzymes (chymotypsin, papain, trypsin) will break it down
39
how is the problem of IgG being degraded solved?
secretory antibody is produced which is specialised for the gut (modified IgG) called secretory IgA Put IgA and IgG in solution of proteases, and IgG will last 10 seconds but IgA will last 8 hours
40
Serum IgG vs Secretory IgA antibodies
2 differences between IgG and IgA: IgA - there are 2 of them and they are dimerized by the small protein called joining proteins dimerization increases the affinity of the antibody for a pathogen- its an adaptation that will cause pathogens to aggregate addition of secretory component- stops the proteases digesting the antibody. It
41
what can IgA be split up into?
IgA1 and IgA2 IgA1 found at the top of the digestive tract and IgA2 is found towards the bottom, where all the serious enzymes are IgA1 has exposed regions – in the hinge regions IgA2 - deleted hinge regions, so no protease susceptible hinge sites
42
mechanism of action of IgG
- Binding to key functional sites on microbes and toxins - Agglutination - Induce inflammation - Recruit immune cells
43
mechanism of action of SIgA
- Binding to key functional sites on microbes and toxins - Agglutination (much better) – 4 sites - Immune exclusion - Intra-cellular neutralisation - Virus excretion - Interactions with non-specific factors (lysozyme, lactoferrin, peroxidases)
44
where do you produce SIgA?
in your glands
45
if a virus has crossed the epithelial layer how can SIgA help?
if virus binds to an SIgA the virus will then get taken back again
46
Approaches to Oral Immunisation
-Attenuated virus (eg polio) -Attenuated recombinant bacterial mutants (eg Salmonella typhi) - Mucosal adjuvants (eg cholera toxin) - Liposomes, microspheres, capsules - Transgenic edible plants Good way of getting vaccines into poorly developed countries
47
systemic vs musocal immunity in terms of primary and secondary responses
systemic - secondary is v diff to primary, its faster, larger production of antibodies etc The mucosal immune system does not work like the systemic in terms of the differences between primary and secondary immunisation mucosal - the second response is only a little better than the primary response, and it also lasts roughly the same amount of time
48
Oral vaccine delivery using GM plants | hep B and potatoes
1. The Hep B surface antigen gene, is transferred from yeast into a plant cell (potato is used as a prototype) 2. Potato plants are regenerated from transformed cells 3. Hepatitis vaccine is correctly expressed by potato plants 4. GM potatoes are harvested that contain the hepatitis vaccine
49
how do you test the concept of oral vaccination | also explain the results from the trial
1. Grow plants which express hepatitis vaccine to maturity and harvest edible tissue. 2. Feed uncooked tubers to animals or humans and analyze immune response results: - Very successful trial - 3 doses to get the level needed to get protection - Cooking the potatoes will denature the enzymes - Good technology for developing countries - If you ask the people in developing countries to grow the potatoes themselves the costs can be reduced even further
50
orally delivered antigens can?
can suppress systemic immunity
51
if an antigen is first encountered through the musocal system, what are the risks?
the systemic immune system may become unresponsive (tolerised) to that antigen eg. Mice get a toxin vaccine – first time is encountered by an injection under the skin – will not produce antibodies in the gut, but will have a good response in the blood another group of mice are fed the tetanus toxin a week before before and then given the injection (systemic) They get gut antibodies (good mucosal response), because the gut has had it’s first encounter by it but they will not produced antibodies in the blood as they have been systemically tolerised to it
52
what is a good example of an autoimmune disease? explain how it works
Diabetes the body starts to recognise insulin/the cells that produce insulin as being foreign - kills off the islets of Langerhans (produce insulin) study where mice were given insulin orally and they didn’t develop diabetes
53
list factors that can affect the induction of oral tolerance how how they can be resolved
(nature of the antigen, dose and frequency of delivery) 1. Tolerance: Soluble antigens Vaccination: Antigen/adjuvant or other formulations 2.Tolerance: Repeated sustained doses Vaccination: Limited number of immunisations 3. Tolerance: High doses Vaccination: Low dose (usually in μg range)
54
are the mucosal and systemic immune systems completely separate?
no but, the mucosal immune system can be stimulated by antigens independently of the systemic immune system
55
where are the sites of antigen stimulation in the mucosal immune system?
usually at specialised sites in GALT, BALT and NALT - these are subdivisions of MALT (mucosa associated lymphoid tissue) in intestinal MALT, M cells are also present GALT - gut associated lymphoid tissue BALT – bronchial associated lymphoid tissue There are structures a bit like peyers patches in the lungs NALT – nasal associated lymphoid tissue
56
what is the major major immunological factor expressed at all mucosal sites?
secretory IgA
57
where do most microbial infections start?
at mucosal sites
58
how are most vaccines administered?
systemically