Immunological Functions and Mucosal Tissues

Question 1

Describe the features of innate immunity

Answer 1

• Prevents infection and avoids disease
• Non-specific
• No memory
• Mediated by: macrophages, epithelial barriers,
  secretions. .

Question 2

Describe features of adaptive immunity

Answer 2

• Responds to infection and prevents disease
• Highly specific response to targeted microbe
• memory
• Mediated by: lymphocytes, antibodies

Question 3

What is systemic immunity?

Answer 3

Immune response originating from bone marrow, spleen, thymus lymph system, blood circulation

Question 4

What is mucosal immunity?

Answer 4

Mucous membrane - eyes, nose, mouth, lungs, gut, genitourinary tract

Question 5

What are the mucosal surfaces?

Answer 5

oral, nasal, lacrimal surfaces gastrointestinal tract, bronchial tract, genito-urinary tract and mammary glands

Question 6

What is the significance of mucosal membranes?

Answer 6

All sites are normally colonised by microbes
Main route of entry for infectious microorganisms

Large surface area specialised for absorption. Gut ~ 200m2 Skin ~2m2

Question 7

What are the innate mechanisms of protection in the mucosal immune system?

Answer 7

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

Question 8

What are the adaptive mechanisms of mucosal immunity?

Answer 8

mucosal/secretory immune system

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

Question 9

What is the mucosal barriers?

Answer 9

Innate: Natural barriers (eg stomach)
	Mucin
	Peristalsis
	Proteolysis
	Microvillus membrane or squamous cell

Question 10

What is the immunological component of the mucosal barrier?

Answer 10

Immunological: Secretory IgA/IgM, IgG

Question 11

What protection does mucosal immunity provide in the mouth?

Answer 11

Serum, saliva and local anitbodies are secreted in the mouth from systemic immunity from blood circulation in the oral cavity

Question 12

What lymphoid cells are present in the gut?

Answer 12

1) Intraepithelial lymphocytes
2) Lymphocytes + macrophages scattered in lamina
propria
3) Peyer’s patches

Question 13

Describe Peyer’s Patches

Answer 13

~200 in body
Epithelial layer beneath which is loads of white blood cells
M cells continuously sample contents of gut

Question 14

What do M cells target for uptake?

Answer 14

Particles and macromolecules:
- cholera toxin, latex particles, horseradish peroxidase,
ferritin

Viruses: eg poliovirus, HIV

Parasites: eg Cryptosporidium

Bacteria: Cholera, salmonella, Campylobacter Yersinia,
Shigella, E. coli

Question 15

Describe how immune cells migrate from Peyer’s Patches

Answer 15

Bacteria from gut sampled by M cells and presented to wbc’s
Starts to activate wbc’s to migrate through mesenteric lymph flow and mature where they migrate to the blood circulation and only target mucosal tissue where they produce antibodies

Question 16

Why is the mucosal system described as ‘common’?

Answer 16

Produce antibodies in all mucosal sites despite interacting with pathogen in loop of gut - WBCs then return to gut

Question 17

Describe the mucosal antibodies

Answer 17

Predominantly SIgA
Found in all secretions and breast milk
Provide passive immune protection in newborn infants

Question 18

Outline the IgG mechanism of action

Answer 18

Binding to key functional sites on microbes and toxins
Agglutination
Induce inflammation (not wanted in GI diseases e.g. crohn’s as epithelial layer is lost)
Recruit immune cells

Question 19

Outline the mechanism of action of SIgA antibodies

Answer 19

Binding to key functional sites on microbes and toxins
Agglutination (much better)
Immune exclusion
Intra-cellular neutralisation
Virus excretion
Interactions with non-specific factors - lysozyme, lactoferrin, peroxidases

Question 20

What are the different approaches to oral immunisation?

Answer 20

Attenuated virus (eg polio)
Attenuated recombinant bacterial mutants (eg Salmonella typhi)
Mucosal adjuvants (eg cholera toxin)
Liposomes, microspheres,
Capsules
Transgenic edible plants

Question 21

How do vaccines compare to oral immunisation?

Answer 21

Vaccines work for longer than just oral immunisation

Question 22

Explain how Oral vaccine delivery is achieved using GM plants?

Answer 22

1. Hep B surface antigen gene is transferred from yeast
   into plant cell ( e.g. potato)
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

Question 23

How would we test the oral vaccine production in plants concept?

Answer 23

• Grow plants which express hepatitis vaccine to maturity
  + harvest edible tissue.
• Feed uncooked tubers to animals/humans + analyze
  immune response

Question 24

Explain oral tolerance

Answer 24

If an antigen is first encountered through the mucosal immune system, the systemic immune system may become unresponsive (tolerated) to that antigen.

Question 25

Explain the effect of orally delivered antigens on systemic immunity?

Answer 25

Orally delivered antigens can suppress systemic immunity

natural mechanism to prevent immune reactions to food and useful commensals?

Question 26

What are the practical considerations of oral tolerance?

Answer 26

Tolerance to dietary foods, breakdown to food allergy.
Oral vaccination and safety
Treatment and prevention of autoimmune diseases

Question 27

What factors affect the induction of oral tolerance?

Answer 27

Induction of oral tolerance can depend on many factors, such as the nature of the antigen, dose and frequency of delivery

Question 28

Outline the vaccinations used for different oral tolerances?

Answer 28

1. Tolerance: Soluble antigens
   Vaccination: Antigen/adjuvant or other formulations
2. Tolerance: Repeated sustained doses
   Vaccination: Limited number of immunisations
3. Tolerance: High doses (eg 20-500 mg bolus)
   Vaccination: Low dose (usually in mg range)

Question 29

How is the mucosal immune system stimulated?

Answer 29

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

Question 30

What is the major immunological factor?

Answer 30

secretory IgA, which is expressed at all mucosal sites

Question 31

Where are vaccines mostly administered?

Answer 31

Most microbial infections start at mucosal sites, but most vaccines are administered systemically