Mucosal immunology Flashcards
MALT
Mucosa-associated lymphatic tissue
Divided into BALT and GALT
BALT
Bronchial associated lymphatic tissue
GALT
Gut associated lymphatic tissue
Why os the mucosal immune system very important?
The biggest immune compartment of the organism
Estimated surfaces area of 400m2, harbours 60% of all effector cells
In direct contact with the outside environment
Continuous antigen stimulation (food, endogenonus flora, pathogens)
Mucosal sites are the ports of entry for many infections and an important target site of vaccine induced protection
The main defence strategies of intestinal mucosa and oropharynx
Endogenous flora
Epithelium and mucus
Regionalised immune system and gut homing of B and T cells
Endogenous flora
10^14 bacteria
Hundreds of different species
Epithelium and mucus
Mechanical barriers (cells, tight junctions)
Specialised epithelial cells (goblet cells, absorptive epithelial cells, M cells, paneth cells)
Antimicrobial substances (defensins, lysozymes, lactoferrin, phospholipases)
Mucins (extgensively glycosylated proteins) form a viscous barrier
Regionalised immune system and gut homing of B and T cells
Wadeyer’s ring (linguinal and palatine tonsils, nasopharyngeal tonsils)
Peyer’s patches
Mesenteric lymph nodes
Intraepithelial immune cells
Lamina proporia immune cells, including sampling DCs
The main defence strategies of intestinal mucosa and oropharynx
Lymphoid complexes along the GI tract
Volume of the rings indicates the relative amount of lymphoid tissue
The largest amount of lymphoid tissue is found in the oropharynx and terminal ileum
Intestinal epithelial cells
Specialised epithelial cells have a number of functions improving defence but not inflammation
Goblet cells
Epithelial cells
M cells
Paneth cells
Goblet cells
Produce mucus
Epithelial cells
Express TLRs
TLR5 expressed on the basolateral surface and intracytoplasmic NLR for bacterial flagellins are activated only upon access of bacteria to the cytosol
M cells
Transport antigens to subepithelial lymphoid structures
Paneth cells
Produce human defensin precursor, HD6 precursor, trypsin
Is it a good thing that ligation of TLRs on the basolateral surface of gut epithelial cells does not promote inflammation?
If it did the entire gut would be inflamed
If it was inflamed it would not be able to absorb nutrients as well
Peyer’s patches and associated immune cells
PPs contain germinal centres for B and T cells
They are located in the distal ileum in areas of follicle associated epithelium
The foetal human small intestine contains on average 60 PPs before week 30 of gestation and their number steadily increases reaching a maximum of about 240 at puberty
Inductive site for immune response
Architecture of Peyer’s patches
There are three main domains
- the follicular area
- the interfollicular area
- follicle associated epithelium
Follicular and interfollicular areas
Lymphoid follicles with a germinal center containing proliferating B lymphocytes, follicular dendritic cells and macrophages
The follicle is surrounded by the corona, or subepithelial dome, containing mixed cells including B cells and T cells, macrophages and dendritic cells
The FAE
Differes from normal epithelium in regards to microvilli regularity and length, and the presence of infiltrating immune cells
Naive lymphocytes
Immigrate into the PP via specialised high endothelial venules
Naive or activated lymphocytes leave the PP via efferent lymphatic vessels at the serosal side of the PPd
M cells features
Small microvilli
Large cell membrane fenestrations
- features enhance antigen uptake from epithelium
Trans-cellular transport of antigen
Exocytosis at the basolateral membrane
Delivery to dendritic cells in dome region of underlying lymphatic structures
Mesenteric lymph nodes
Located at the base of the mesentery and collect lymph, cells and antigens from the intestinal mucosa
Main site for oral tolerance induction
MLN drain lymph from intestinal mucosa
Many food antigens will bypass lymphatic tissue and reach the liver through the portal vein
Immune cells in liver sinuses
Have an important function in protecting us from microbes/ microbial products in the portal vein
Lamina proporia and intraepitheial lymphocyte comprtment
IEL are situated in the basolateral part of the epithelium
Irregular shape
Long extensions in close contact with neighbouring epithelial cells
Occur in variable numbers along the gut
Up to 12% eosinophils in IEL preparations
IEL in the small intestine
Majority comproised of TCRalphabeta and CD8alphaalpha
Proportion increases in the distal region and may reach as much as 30% of the total IEL population in that area of the colon
Intraepithelial cells subdivided into 3 main groups
TCRalphabeta and CD8alphabeta
TCRalphabeta and CD4alphabeta
TCRalphabeta and CD8alphaalpha
MIC-A and MIC-B
Ligands for the NK cell activating receptor NKG2D
Also found on CD8alphaalpha T cells
Thymus leukaemia antigen
An MHC-lb molecule that does not enable peptide binding
Mucosal T cells
Differentiation influenced by epithelial cells and DCs
T regulatory cells produce IL-10 and are crucial in establishing and maintaining food tolerance and class switch, including TGF-B and others
Th1 cells produce IFN-y and are important in killing virally infected epithelial cells
Th2 cells may be induced by worm infection
Dendritic cells
Sit in the lamina propria
Have long extensions reaching through the epithelium to sample contents of the intestinal tube
Such antigens are presented to the T cells
Mucosal B cells and IgA
Secretory component binds to J chain and enable trans-endothelial transport of dimeric IgA
SIgA exerts cross reactive innate like and infection or vaccine induced protection against epithelial invasion
pigA and pigM exert non-inflammatory effects inside and below the epithelium
SIgA antibodies play no protective role following invasion of infectious agents
IgA
Main antibody in secretions
Against food antigens provides immune exlusion
Activates the complement system only weakly
Secretions of IgA (coupled to J chain) depends on a trans-cellular transport mechanism
B and T cell homing
Activated T cells and circulating memory cells exit the lymph node via efferent lymphatics and return to circulation through thoracic duct
Reach target tissues via blood stream
Different combinations of homing receptors guide effector cells to different tissues
At tissue sites, upregulation of respective ligand moecules will be related to the situation in these tissues
T cells migrate through circulation
Intergrin and chemokine signals direct their emigration into tissues
Imprinted T cells have specific ket that allows access to restricted tissues under normal homeostatic conditions
