Immunological Functions of the GI Tract Flashcards

1
Q

State the areas of the body involved in immune function

A
  • Mucous membranes of bronchi and gut
  • Skin
  • Phagocytic cells, lungs, liver, spleen
  • Tonsils, adenoids
  • Thymus
  • Lymph nodes and lymphatic vessels
  • Spleen
  • Peyer’s patches on small intestine
  • Bone marrow
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2
Q

Describe innate and adaptive immunity

A
  • Innate -
  • Prevents infection and avoids disease
  • Non specific
  • No memory
  • Mediated by macrophages, epithelial barriers and secretions etc
  • Adaptive -
  • Responds to infection and prevents disease
  • Highly specific response to targeted microbe
  • Memory
  • Mediated by lymphocytes and antibodies
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3
Q

Describe systemic and mucosal immunity

A
  • Systemic immunity - bone marrow, spleen, thymus, lymph system, blood circulation - areas which are fully inside the body (not exposed to external environment)
  • Mucosal immunity - eyes, nose, mouth, lungs, gut, GU tract (areas of the body exposed to the external environment that are protected by secretions)
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4
Q

Describe the mucosal immune system

A
  • Mucosal surfaces - oral, nasal, lacrimal surfaces gastrointestinal tract, bronchial tract, genito-urinary tract and mammary glands
  • All sites are non sterile and colonised by microbes
  • Main route for entry for infectious microorganisms
  • Large surface area specialised for absorption
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5
Q

State the innate and adaptive mechanisms of the GI tract

A
  • Innate mechanisms - mucin, peristalsis, antimicrobial peptides and proteins e.g. lysozyme, lactoferrin, phagocytes
  • Adaptive mechanisms - mucosal/secretory immune system - secretory IgA/IgM/IgG
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6
Q

Describe the sources of serum, saliva and local antibodies in the oral cavity

A
  • Salivary glands produce saliva
  • Can also get serum components enter the oral cavity through the gums
  • Lymphoid tissues near the oral cavity can produce antibodies which then enters the tissues of the mouth via the peripheral blood supply
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7
Q

Describe what the gingival crevice is and what it allows

A

There is a joint where the tooth goes into the jaw bone which has to be covered by skin - it is difficult to seal this area off to prevent infectious agent entry - forms a gingival crevice

Gingival crevice allows serum blood to seep out of the gun and onto the tooth as well

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8
Q

State the types of lymphocytes in the gut

A
  1. Intra epithelial lymphocytes
  2. Lymphocytes and macrophages scattered in the lamina propria
  3. Peyer’s patches
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9
Q

Describe the role of peyers patches - what they are- what they are responsible for

A

Peyer’s patches - very important to induce an immune response in the gut as the antibody response is much higher in areas of the gut with peyer’s patches than areas without - it is also responsible for inducing immune responses elsewhere in the gut

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10
Q

Describe the white blood cell distribution in the gut wall

A
  • There are very few white blood cells in the top layer of the gut wall but there are occasional cells called langerhans cells - dendritic cells - have projections into the gut lumen to pick up microbes
  • Most of the white blood cells lie underneath the epithelium
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11
Q

Describe the structure of the peyers patches

A
  • The epithelium of the gut is raised into a little mound with cells called M cells in the epithelium
  • M cells sample the fluid from the gut lumen and act as antigen presenting cells to cause the correct response from lymphocytes cells directly below the M cells
  • Underneath there is a dense collection of white blood cells
  • These are used to take samples of what is present in the lumen of the gut
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12
Q

Describe the differences of M cell mechanisms

A
  • M cells are targets by some microbes for uptake such as viruses like poliovirus and HIV
  • They can also take in cholera toxins
  • They also intake parasites like cryptosporidium
  • They can uptake bacteria like cholera, salmonella, campylobacter yersinia, shigella and E coli
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13
Q

Describe how immune cells migrate for peyers patches

A
  • After M cells present antigens the lymphocytes become activated
  • Some of these lymphocytes will migrate out of the peyer’s patch and be taken up by the lymphatic drainage - lymphatic vessels into the nearest lymph node which is called the mesenteric lymph node
  • These lymphocytes will then mature into mature lymphocytes or plasma cells that we want to make like antibodies
  • These mature cells then go into the blood supply - they then start to produce antibodies so they should be found in the blood supply
  • Yet this is not the case because the lymphocytes have homing proteins which make sure they transport from the blood circulation to mucosal surfaces
  • These surfaces include back to the small intestine, the eyes (lacrimal glands), mouth, mammary glands, GU tract and lungs
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14
Q

State the form the majority of mucosal antibodies come in an where they are found

A
  • Predominantly SIgA
  • Found in all secretions and breast milk
  • Provide passive immune protection in newborn infants
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15
Q

Compare serum IgG and secretory IgM in terms of structure

A
  • IgG consists of 2 heavy and 2 light chains bonded by disulphide bonds to form a Y shape which has 2 variable regions antigens can bind to
  • IgA consists of 2 IgA molecules - still has 2 heavy and 2 light chains bonded by disulphide bonds but they differ from IgG as they have sequence differences
  • These two IgA molecules are bound together by a third protein called joining protein (they are dimerised) - this means IgA can now bind to 4 antigens
  • There is then another protein called the secretory component wrapped around the dimerised IgA that provides protection against degradation - it is wider so can catch more microbes but is more ope to attack by enzymes
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16
Q

Describe the mechanism of IgG and secretory IgA

A

IgG -
- Binding to key functional sites on microbes and toxins
- Agglutination
- Induces inflammation
- Recruits immune cells

Secretory IgA -
- Binding to key functional sites on microbes and toxins
- Agglutination - stops microbes getting past mucus layer of the gut
- Immune exclusion
- Intracellular neutralisation
- Virus excretion
- Interactions with non specific factors - lysozymes, lactoferrin, peroxidases

17
Q

State the approaches to oral immunisation

A
  • Attenuated virus e.g. with polio
  • Attenuated recombinant bacterial mutants e.g. salmonella typhi
  • Mucosal adjuvants e.g. cholera toxin liposomes, microspheres
  • Capsules
  • Transgenic edible plants
18
Q

Describe the systemic response to primary and secondary challenge and why mucosal immunity has an issue

A
  • Upon the first immunisation after about 14 days the first primary immune response will be produced
  • Memory is induced so upon a secondary immunisation the response is much greater as antibodies can be produced at a faster rate and there is a slower decrease in response afterwards
  • One of the issues about mucosal immunity is that we don’t see the memory response upon a secondary immunisation
19
Q

Describe how oral vaccines have been given using GM plants

A

1995 - injection of hepatitis vaccine from plants gave an immune response equivalent to the yeast derived vaccine

  1. The Hepatitis B surface antigen gene is transferred from yeast into a plant cell like potatoes
  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

Testing the concept of oral vaccine production in plants -
1. Grow plants which express hepatitis vaccine to maturity and harvest edible tissue
2. Feed uncooked tubers to animals or humans and analyse immune responses

20
Q

Describe what oral tolerance is

A
  • Orally delivered antigens can suppress systemic immunity
  • Natural mechanism to prevent immune reactions to food and useful commensals?
  • If the antigen is first encountered through mucosal immune system the systemic immune system may becomes unresponsive to that antigen
21
Q

Describe the practical considerations surrounding oral tolerance

A
  • Tolerance to dietary foods, breakdown to food allergy
  • Oral vaccination and safety
  • Treatment and prevention of autoimmune disease - can use oral intolerance to an advantage and use oral doses or insulin for example to stop development of diabetes
22
Q

Explain why oral tolerance doesn’t mean we cant use oral vaccination

A

Induction of oral tolerance can depend on many factors such as the 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 dosage