Mucosal immunology Flashcards
MALT
Mucos-associated lymphatic tissue
Includes
- BALT- bronchial
- GALT- gut-associated
Importance of mucosal immune system
Largest immune compartment
- 60% of all effector cells
In direct contact with outside environment
- Ports of entry for many infections
Constantly stimulated by antigens
Target site for vaccine-induced protection
Main defence strategies of intestinal mucosa & oropharynx
Endogenous flora
Epithelium and mucus
Regionalised immune system
Gut homing of B and T cells
Endogenous flora of intestinal mucosa & oropharynx
10^14 bacteria of hundreds of species in the body
- Compete with pathogenic bacteria/ organisms
Commensal gut flora induces low affinity IgA responses.
- Food specific responses
Features of the epithelium and mucus that provides immunological defence
Tight junctions in epithelial cells
Specialised cells
- Goblet
- M cells
- Paneth cells
- Absorptive epithelial cells
Antimicrobial substances
Mucins
- viscous barrier
Regionalised immune system
Waldeyer’s tonsillar ring
- Lymphoid tissue in the pharynx
Peyer’s patch
- Small intestines
Mesenteric lymph nodes
Intrapethelial immune cells
Lamina propria immune cells
Lymphoid complexes in the GIT [5]
Waldeyer’s ring
- one of the largest
Gastric antrum tissue
Patches in the small bowel (payer’s)
Terminal ileum lyhoid tissue
- One of the largest
Large bowel patchers
Goblet cells
Provides a physics-chemical barrier by producing mucus
Innate immune receptors and epithelial cells
Express TLR depending on the region
- 2, 4-7, 9.
- Undergoes surface TLR ligation
TLR5
- Basolateral surface (in contact with invading bacteria)
NLR
- Intracytoplasm
- Recognises flagellants
- In contact with bacteria in the cytosol
Surface TLR ligation
Mechanism of the intestinal epithelial cells.
Causes:
- Tightening of epithelial junctions
- Increase of proliferation and motility
NOT inflammation
M cells
Specialised epithelial cells
Transports antigens transcellulary to sub epithelial lymphoid structures.
- Exocytosis at basolater membrane
- Delivers dendritic cells to lymphatic structures
Structure
- Small microvilli
- Large cell membrane fenestrations
Paneth cells
Specialised epithelial cells
Produces antimicrobial peptides
- Human defensive 5 precursor
- HD6
- Trypin (activates HD5, HD6)
Peyer’s patch
Lymphoid tissue in small intestines.
- Distal ileum, follicle associated epithelium (FAE)
Contains 3 domains
- Follicular
- Interfollicular
- FAE
Site where immune responses are induced
- Has B and T cell germinal centres
Connected to circulation via endothelial venlues (where naive lymphocytes migrate in) and lymph vessels (where the lymphocytes exit out)
240 patches by puberty (60 in fetus)
Follicular and interfollcular areas of payer’s patch
Germinal centre containing;
- B-lymphocytes
- Follicular dendritic cels
- Macrophages
Surrounded by corona/ sub epithelial cells, containing cells above.
FAE
Follicle associated epithelium
Different microvilli regularity and length compared to normal epithelium
Contains infiltrating immune cells
Mesenteric lymph nodes
Collects lymph, cells and antigens from intestinal mucosa.
- Main site for oral tolerance induction
Although many food antigens bypass intestines and enter liver.
Mucosal IgA
Main antibody in secretions
- When coupled to J chain, depends on trans-cellular transport
Those secreted against food antigens= immune exclusion
Activates the complement system
T-cell dependent IgA class switching in the gut
T-cell dependent:
- Dendritic cells in sub-epithelial zone take up bacterial antigens—> present to Cd4 after migrating to inter follicular zone
- Activated helper cell stimulates IgM/IgD B cells–> class switch (via CD40L, TGF-B)
- Ig A class switch stimulated by NO production from DCs
T-cell independent IgA class switching in the gut
TLR ligand sections activate DCs.
DCs activate IgM/IgD B cell class switch to IgA via inducing TGF-Beta.
Th17 cells in the gut
Produces IL-17, IL-22.
- Regulate the production of musicians and defensins
Th2 T cells in the gut
Secrets IL-4, IL-13
- Can be induced by worm infection
- Increases fluid, mucus secretions
- Increases bowel motility + smooth muscle contraction
Th1 T cells in the gut
Produces IFN-g
- kills virally infected epithelial cells
Treg cells in the gut
Establishes and maintains food tolerance
- Secretes IL-10
also stimulates class switch via TGF-b
Dendritic cells in the gut
Located in the lamina propia.
Present antigen to T and B cells to stimulate class switching
Produces IL-16, retinal acid
