Immunological Functions of the (Alimentary Tract) Mucosal Tissues Flashcards
What is the difference between innate and adaptive immunity?
Innate:
Prevents infection and avoids disease
Non-specific
No memory
Mediated by macrophages, epithelial barriers, secretions
Adaptive:
Responds to infections and prevents disease
Highly specific response to targeted microbe
Memory
Mediated by lymphocytes, antibodies
Another way of dividing the immune system is…
Systemic immunity:
Bone marrow, spleen, thymus lymph system, blood circulation
Mucosal immunity:
Mucous membranes- eyes, nose, mouth, lungs, gut, genitourinary tract
What is the mucosal immune system?
Mucosal surfaces; oral, nasal, lacrimal surfaces, gastrointestinal tract, bronchial tract, genito-urinary tract and mammary glands
All sites are normally colonised by microbes
Main route of entry for infectious microorganisms
Large surface area specialised for absorption
Innate mechanisms of protection include; mucin, peristalsis, antimicrobial peptides and proteins e.g. Lysozyme, lactoferrin; phagocyte
Adaptive mechanisms are also present; mucosal/secretory immune system
Most discriminate between harmful pathogens and harmless antigens- foods and commensal bacteria
What does the mucosal barrier consist of?
Innate: Natural barriers (e.g. stomach) Mucin Peristalsis Proteolysis Microvillus membrane or squamous cell Immunological: Secretory IgA, IgM and a little IgG
What are the sources of serum, saliva and local antibodies in the oral cavity?
Saliva contains the majority of immune components
The second source comes through the hard tissue butting up against the soft tissue of the gingival
In that crevice there is only one or two cell thick layers of epithelium
Through there comes out fluid, any blood which flows through the gingivae is exuded out through the gingivae and comes out into the gingival fluid (not red because it doesn’t contain RBCs- too big)
This also happens other places such as the gut
What are the lymphoid cells in the gut?
1) Intra-epithelial lymphocytes
2) Lymphocytes and macrophages scattered in the lamina propia
3) Peyer’s patches
Dendrites can sample outside of the epithelium
Peyer’s patches are an organisation/grouping of lymphocytes similar in structure and function to lymph nodes
What are M cells?
An antigen presenting cell (like a macrophage)
Lymphocytes are right beneath them in direct contact
The M cells are taking tiny samples of gastrointestinal fluid
And the reason L cells are so close as M cells will just have to pass the sample across a very small space in case there is a pathogen or foreign molecule
What are the M cell targets for uptake?
Particles and macromolecules- e.g. cholera toxin, latex particles, horseradish peroxidase, ferritin
Viruses e.g. poliovirus, HIV- they specifically go into the body via the M cells
Parasites e.g. cryptosporidium
Bacteria- e.g. cholera, salmonella, campylobacter yersinia, Shigella, E.coli
These like to go in through the M cells
How does the migration of immune cells from Peyer’s Patches?
As soon as an antigen comes across the M cell and gets passed to the lymphocyte underneath which gets activated and start to proliferate
What happens after is that they start to migrate; they will move out of the Peyer’s patch, through the lymph drainage and through the lymphatic system until they get to the mesenteric lymph nodes
The mesenteric lymph nodes are a group of lymph nodes that drain lymphatic fluid from the gut
They then mature a little in there and they move on
Eventually, they move back into the blood circulation through the thoracic duct
What happens to the immune cells after?
Now in the blood system, they home to mucosal sites along the GI tract as long as other mucosal sites
We call this the common mucosal immune system
The same process can happen in the tonsils
What are mucosal antibodies like?
Predominantly SIgA
Found in all secretions and breast milk
Provide passive immune protection in new born infants
What is the difference between serum IgG and secretory IgA antibodies?
The secretory antibody, the basic components are joined by something called the joining component
This joining component sticks to the bottom end and dimerises the antibody
This allows it to recognise four different antigens as opposed to two
This is important in aggregation (clumping the bacteria together)
The other thing differentiating it from the normal antibody is the secretory component
The intestinal tract is designed to break down components, but these will break down anything including IgG
What the secretory component does is wrap around the antibody protecting it from those enzymes
What are the two types of IgA?
There are two types of IgA- 1 and 2
IgA 1 has a hinge region to allow flexibility
The amino acid making up this region is quite short with repeats
The bacteria have recognised this as a weak point and now produce enzymes to break down this specific region
IgA2 has adapted and doesn’t have an exposed hinge region
What are the mechanisms of action of antibodies IgG and IgA?
IgG:
binding to key functional sites on microbes and toxins
Agglutination
Induce inflammation
Recruit immune cells
SIgA
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
Does not induce inflammation because inflammatory gut is not nice
What are the different approaches to oral immunisation?
Attenuated virus (e.g. polio) Attenuated recombinant bacterial mutants (e.g. salmonella typhi) Mucosal adjuvants (e.g. cholera toxin) Liposomes, microspheres Capsules Transgenic edible plants
How can an oral vaccine be delivered using GM plants?
- Injection of hepatitis vaccine from plants gave an immune response equivalent to the yeast-derived vaccine.
- The Hep B surface antigen gene, is transferred from yeast into a plant cell (potato is used as a prototype).
- Potato plants are regenerated from transformed cells
- Hepatitis vaccine is correctly expressed by potato plants
- GM potatoes are harvested that contains the hepatitis vaccine
