Immunological features of the alimentary tract Flashcards

1
Q

the mouth is what?

A

a major portal for infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are located at the top of the throat?

A

Tonsils and adenoids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how can we split the immune system up?

A

innate vs adaptive

mucosal vs systemic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how might the bacteria end up in the faeces?

A

peristaltic waves push the bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

the mucosal surfaces are what?

A

main route of entry for infectious microorganisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is saliva made up of?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

lysozyme

A

breaks down bacteria phagocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

lactoferrin

A

hoards iron to stop bacterial growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

phagocytes

A

engulf microbes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

the mucosal immune system must do what?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

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

A

develop food allergies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

name some mucosal barriers

A

innate (natural barriers, eg. stomach)

  • Mucin
  • Peristalsis
  • Proteolysis
  • Microvillus membrane

immunological

  • Secretory IgA/IgM
  • IgG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
Q

peyers patches sample what?

A

M cells in the peyers patch sample what’s in the gut – look for what shouldn’t be there

26
Q

Peyer’s Patches

A

Covered in a single layer of columnar epithelial

dome, underneath the patch is lots and lots of WBC’s

27
Q

what is the peyers patch important in?

A

recognising the vaccine, initiating mucosal immune response

28
Q

M cells

A

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
Q

how is the pathogen taken up by the WBC so quickly after it crosses the first barrier?

A

because the gap between the external surface of the gut and the first lymphocyte encountered by the WBC is very small

30
Q

why might pathogens target M cells as their route of entry?

A

because the M cells are constantly sampling (active), and it will pick up nanoparticles (like viruses)

31
Q

name a virus that specifically targets the M cells

A

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
Q

migration of immune cells from Peyer’s Patches

A

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
Q

Introducing pathogen in the gut will enable you to see what?

A

a response in all the other mucosal sites

34
Q

Common mucosal immune system

A

common because there is an interlinkedness between the immune response and where you see the immunity

35
Q

Mucosal Antibodies

A
  • Predominantly SIgA
  • Found in all secretions and breast milk (sterile)
  • Provide passive immune protection in new-born infants
  • traditional treatment for conjunctivitis
36
Q

what are antibodies?

A

soluble proteins present in mucosal secretions

37
Q

in the blood what antibody do we predominantly produce?

A

IgG antibodies

38
Q

why are less IgG antibodies produced in the gut?

A

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
Q

how is the problem of IgG being degraded solved?

A

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
Q

Serum IgG
vs
Secretory IgA antibodies

A

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
Q

what can IgA be split up into?

A

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
Q

mechanism of action of IgG

A
  • Binding to key functional sites on microbes and toxins
  • Agglutination
  • Induce inflammation
  • Recruit immune cells
43
Q

mechanism of action of SIgA

A
  • 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
Q

where do you produce SIgA?

A

in your glands

45
Q

if a virus has crossed the epithelial layer how can SIgA help?

A

if virus binds to an SIgA the virus will then get taken back again

46
Q

Approaches to Oral Immunisation

A

-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
Q

systemic vs musocal immunity in terms of primary and secondary responses

A

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
Q

Oral vaccine delivery using GM plants

hep B and potatoes

A
  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
Q

how do you test the concept of oral vaccination

also explain the results from the trial

A
  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
Q

orally delivered antigens can?

A

can suppress systemic immunity

51
Q

if an antigen is first encountered through the musocal system, what are the risks?

A

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
Q

what is a good example of an autoimmune disease? explain how it works

A

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
Q

list factors that can affect the induction of oral tolerance how how they can be resolved

A

(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

  1. Tolerance: High doses
    Vaccination: Low dose (usually in μg range)
54
Q

are the mucosal and systemic immune systems completely separate?

A

no

but, the mucosal immune system can be stimulated by antigens independently of the systemic immune system

55
Q

where are the sites of antigen stimulation in the mucosal immune system?

A

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
Q

what is the major major immunological factor expressed at all mucosal sites?

A

secretory IgA

57
Q

where do most microbial infections start?

A

at mucosal sites

58
Q

how are most vaccines administered?

A

systemically