The Mucosal Immune system Flashcards
What is mucosa?
Covers the walls of the body cavities. Its a membrane made up of:
- epithelial cell layer
- lamina propria
- thin smooth muscle layer
Its kept moist via secretions from mucous glands and is the largest contact area towards our surroundings.
Name 3 challenges of the mucosae
They need to be permeable but also work as a barrier.
It needs to recognize pathogens from normal commensals, as well as
nutrient uptake, gas exchange from innocuous antigens.
How does the epithelia function as a physical & functional barrier?
- Microvilli affects microbe adhesion
- Tight junctions decreases interepithelial permeability
- Fast turnover of infected IEC (intestinal epithelial cells), or in other words they are replaced fast
- Glycocalyx layer are carbohydrate structures with proteases etc.
- Mucus induced by physical, chemical or infectious stimuli is semipermeable, enhances IEC regeneration, ”captures” bacteria
and is degraded by mucinases
What are commensals?
Commensals are normal gut microbiota. They contribute to mucus synthesis. They compete with pathogenic microbes with space and nutrients and also produces bacteriodical factors.
Name the innate functions that protect the mucosa
- Antimicrobial peptides
e g defensins, prod by Paneth cells,
hydrophobic w +-charged domain,
create pores in cell membranes - Neutrophils, macrophages,
mast cells, innate lymphoid cells (ILC) - Humoral factors
Such as lactoferrin (binding Fe2+), lysozyme (lysing cell walls), peroxidase and C3, C4, factor B
What are the innate lymphoid cells and how are they induced?
They are the first line of defense until the adaptive system is activated.
There are 3 subsets:
- IL-15, IL-12 induces ILC1 and NK-cells which produces effector cytokines.
ILC1 => IFN-y and TNF-a
NK cells => Granzymes, perforrin and IFN-y - Helminths induces ILC2 which releases the cytokines IL-4, IL-5 and IL-13
- Extracellular pathogens induces ILC3 which releases IL-17 and IL-22
Describe how IgA is transported over mucous membranes and what consequences this lead to for the IgA structure and function.
- Dimeric IgA binds to poly-Ig receptor on basolateral side of epithelial cell in mucous membrane.
- Receptor and IgA is endocytosed and stored in vesicle. Enzymatic cleavage occurs, creating a dimeric structure with J-chain and secretory component (sIgA).
- It is then released in the lumen. SIgA is resistant to proteolysis and provides anti-inflammatory defense, meaning it will not activate complement, act as an opsonin or other factors.
What are Peyers patches and what are they made up of?
It’s an organised lymphoid tissue in intestinal submucosa.
Its luminal part is covered up by FAE (Follicle-Associated Epithelium) which has no digestive enzymes, less microvilli and M cells in it.
B & T cells, macrophages, DC resides under the epithelial layer.
Where can you find M cells? What is the function of M cells and how are they structurally adapted to this function?
M cells are located in the epithelium covering the Peyer’s patches in the ileum in the small intestine. Their function is to transfer antigens from the intestinal lumen to the immune cells in the Peyer’s
patches, including e g dendritic cells. They lack microvilli and mucus to be able to efficiently endocytose the antigens and then release them.
There are a specific type of lymphocyte that is attached to the epithelial layer, which is it and what does it do?
CD8 + Cytotoxic IELs protect against intracellular pathogens. There is limited diversity of these T cells in comparison to the circulating T cells.
T-cell independent class switching to IgA2, is more resistant to proteolysis than IgA1. How is Ig2 made?
ECs & DCs sense TLR ligands and produces APRIL & BAFF to the B cell. The B cell then produces IgA2 instead of IgA1
How does the body build up a mucosal tolerance of intake of food? (Oral tolerance)
Food proteins induce an active form of immunological tolerance in the systemic and mucosal immune systems; this tolerance may be mediated by Tregs producing IL-10 or TNF-beta.
Studies show that food proteins (e.g. ovalbumin) taken in orally under a longer time period, build up an oral tolerance. 6 days later if the food protein (antigen) is injected in combination with adjuvant, there was a lower ovalbumin-specific systemic immune response. (compare with 1 individ that ate proteins before and one that didn’t)
A similar suppression of the immune responses is observed after the administration of proteins into the respiratory tract, giving mucosal tolerance.
Why are Peyers patches important?
Peyer’s patches act as immune surveillance centers. They help monitor the gut for the presence of pathogens, such as bacteria and viruses, and initiate immune responses when necessary.
M cells captures and transports antigens (foreign substances) from the gut lumen to immune cells within the patch. This allows the immune system to sample and respond to potential threats in the gut.
Within Peyer’s patches, B cells differentiate into plasma cells and produce immunoglobulin A (IgA) antibodies. IgA is a crucial component of the mucosal immune system and helps protect against pathogens in the digestive tract.
The mucosa-associated lymphoid tissue (MALT) initiates immune responses to specific antigens encountered along all mucosal surfaces. Describe the mechanism behind activated lymphocytes migrate to the mucosa.
- Naïve lymphocytes reach MALT-sites, e.g mesenteric lymph nodes. The naïve cells are activated by antigen-presentation by dendritic cells.
- Effector lymphocyte cells mature in MLN and upregulate a4b7 integrin & CCR9 and then return to circulation.
- Effector cells specifically return to mucosal tissue. Mad-CAM1 is a mucosal addressin that attracts alfa4beta7. CCL25 is a mucosal chemokine that attracts CCR9.
Give an example of the mechanism behind activated lymphocytes migrate to the mucosa.
DCs that are present in the lymph node have a specialized enzyme called RALDH that converts vitamin A into retinoic acid. The lymphocytes that are exposed to retinoic acid upregulate the markers a4b7 integrins and CCR9 will which have corresponding adressins and chemokines that attracts them to the mucosa.
Retinoic acid also induces the production of IgA in B-cells as well as Tregs
