Lecture 13 - Mucosal Immunity Flashcards
What are the components of the mucosal immune system?
- GIT
- Respiratory tract
- Urogenital system
- Breast tissue
What is MALT?
Mucosal associated lymphoid tissue
What is GALT?
Gastrointestinal associated lymphoid tissue
What is the structure of the GIT epithelium?
- Villi made up of enterocytes
- Goblet cells
- Brush border forming microvilli on enterocytes
- Blood supply, lymphatics
- Peyer’s patches
- Lamina propria
What does the epithelium of the GIT potentially experience much immune stimulation?
Because around 100g of protein passes through our gut daily
What is the function of the distal end of the villous?
Absorption
What is the function of the proximal end of the villous?
Secretion
Division
What types of cells are there in the gut epithelium?
Goblet Enterocytes Paneth cells M cells Intra-epithelial lymphocytes
What is the function of goblet cell?
Secrete:
• mucin
• lysozyme
• lactoferrin
What is the function of Paneth cells?
Secrete:
• defensins
Where are the lymphocytes in the villi located?
In the lamina propria
In between the enterocytes: intraepithelial lymphocytes (IEL)
What are the pros / cons of a large surface area of the gut epithelium?
Pro: lots of area for secretion / absorption
Cons:
• vulnerability to microbes
• vulnerability to food antigens
What is thus the general goal of the GALT?
Dampen down the immune response
Tolerance of harmless non-self antigens
What are the innate defences of the gut?
- Peristaltic flushing action
- Acid
- Mucous
- Tight junctions
- Antimicrobial factors
- Cytokines / chemokines
- Cells (lymphocytes, macrophages)
- Glycocalyx
What are the physical and chemical barriers of the surface of the gut?
Glycocalyx
Mucin
In general, how does the mucosal immune system vary from the systemic immune system?
Systemic: structure
Mucosal: not overly structured
Compare the antigen sampling in lymph nodes of the systemic and mucosal IS
Systemic: antigen draining from tissue
Mucosal: direct sampling, lymphocytes present in the tissue
Compare the lymph nodes in systemic and mucosal
Systemic: capsulated, must enter by afferent lymphatics
Mucosal: not encapsulated, antigen may be sampled directly from the lumen of the gut
Where are M cells found?
At the tip of the Peyer’s patch
What is the structure of a Peyer’s patch?
M cell
SED: sub-epithelial dome
Follicles
Where do lymphocytes become activated in the Peyer’s patch?
The follicle
In the mucosa, where are the two places that lymphocytes are found?
- Effector site, IEL
* Follicle of Peyer’s patch
What is the name for the enterocytes on the Peyer’s patch?
Follicle associated epithelium
Which cells sample the contents of the lumen in the Peyer’s patches? Where are these cells located?
• M cells
present at tip of dome
• APCs
present in the SED
Do all cells of the gut have microvilli?
No the M cells don’t
Describe the structure of the M cell
- No microvilli
- No glycocalyx
- No mucin
- No MHC II –> not an APC
Describe the function of M cells
- Sample anitgen from lumen by phagocytosis
2. Antigen delivered to APCs in the SED
Where are APCs located in the mucosa?
- SED
* Lamina propria
What is the lamina propria?
Loose connective tissue under the GIT epithelium
Contains APCs and Lymphocytes
What happens once denritic cell take up antigen?
Move to:
• Follicle
• Mesenteric lymph node
to present the antigen to T cells
Which T cells are most often induced in mucosal immunity?
What are the functions of these Th cells?
Treg (dampening)
Th2 (antiviral)
Which isotype is favoured in mucosal immunity?
Secretory IgA
How are T lymphocytes trafficked back to the mucosa?
- DCs induce expression of integrin a4B7 and receptors for mucosal chemokines on lymphocytes
2a. a4-B7 binds to MAdCAM1 on mucosal endothelium
2b. Lymphocytes binds the mucosal chemokines and undergo chemotaxis
What is MAdCAM1 and what does it bind to?
Where is MAdCAM1 present?
It is an addressin
It is found on the endothelium (capillaries) of the GIT
It binds to a4-B7 integrin on lymphocytes
Where are naive lymphocytes activated in the mucosa?
- Follice of Peyer’s patches
2. Mesenteric lymph node
What happens when a DC in the Lamina Propria takes up antigen?
- Migrates to Mesenteric lymph node
2. Presents antigen to naive lymphocytes
What is the effector site of the GALT?
The lamina propria / villus
What happens back at the effector site?
- B cells produce IgA
- CD8+ cells protect against intracellular infections
- CD4+ cells: regulation
Where do lymphocytes go once activated?
- Drain from Mesenteric lymph node to thoracic duct
- Re-enter circulation
- Circulate back to site of infection (GIT), as well as the rest of the gut epithelium
- At site of infection, they are selected out of the blood stream by MAdCAM1 and a4 B7 interactions and chemokines
What happens to activated B cells?
- Enter blood
- Return to effector sites
- Make and secrete IgA into lumen
What is the structure of secretory IgA?
- Dimer
- J chain
- Secretory component
What is the structure of IgA in the blood?
Monomer
What is the structure of secretory IgM?
Pentamer
Describe the process of secretion of IgA?
- IgA binds to pIgR on basal surface of enterocyte
- Endocytosis
- Transcytosis
- Exocytosis with some of secretory component still attached
What is the structure of the secretory component?
It is part of the pIgR that was on the basal surface of the enterocyte that didn’t get cleaved
What is the function of the secretory component?
Prevents proteolysis of the IgA
What is the function of sIgA? (5)
- Blocking epithelial attachment of bacteria
- Neutralisation of toxins
- Neutralisation of intracellular antigens
- Transcytosis of antigen in lamina propria into the lumen
(• weak opsonin, however)
Describe how toxin in the lamina propria may be neutralised
- IgA in the lamina propria binds the toxin
- IgA binds to pIgR and is transcytosed across the cell with the toxin
- Toxin + IgA dumped into lumen
How are T cells skewed towards Treg, Th2 and Th17?
TGF-beta
What are the protective factors of the respiratory tract?
- Mucociliary elevator
- Surfactant containing microbicidals
No mucus, however
What is the function of surfactant?
- Binds and removes pathogens
* reduces surface tension in the alveoli
Where are the inductive sites of the respiratory tract?
What does this mean?
- Adenoids
- Tonsils
Here, there are M cells that sample antigen and lead to activation of the adaptive immune response
Where are the effector sites of the respiratory system?
- Salivary glands
- Lacrimal glands
- Bronchi
What does tolerogenic mean in reference to MALT?
It means that the predominant response of the immune response is suppressive, not reactive
Describe the mucous in the respiratory tract
No mucous
Think about it: it would clog the alveoli and make it ineffective for gas exchange
What is the role of enterocytes in the immune response?
- cytokine production (TGF-beta)
* defensin production
What are the antimicrobial compounds found in the gut?
- Lactoferrin
- Bile salts
- Complement
- Defensins
