Flashcards in Mucosal immunology of the GI tract Deck (30)
What is the GALT?
The gut associated lymphoid tissue.
This includes the adenoids, the tonsils, the appendix, the peyer's patches in the small intestine and the large intestine.
What does the small intestine have that the large intestine does not have?
Paneth cells (to secrete defensins)
Peyer's patches for antigen sampling and immune activation
Where are immune cells found in the small intestine?
They can be found in organised tissue - Peyer's patches
And throughout the lamina propria
What immune cells are found in the small intestine?
lamina propria effector T cells
IgA secreting plasma cells
What are the roles of the immune cells found in the intestines?
Initiate a local immune response
Carry out effector functions to clear any infection
What sort of immune cells are found in the epithelium, and what is their function there?
Innate immune cells. These capture antigens and have an effector function.
What is the function of the immune cells found in Peyer's patches and lymphoid follicles?
Antigen capture and initiation
What sort of immune cells are found in the lamina propria?
Where can antigen capture occur?
Both in Peyer's patches and directly across the epithelium. Dendritic cells can extend processes across the epithelial layer to capture antigens from the lumen of the gut.
What specialised cells are found in the epithelium which covers Peyer's patches?
What do these cells do?
M cells (m stands for microfold) which have characteristic membrane ruffles.
The M cells take up antigens by endocytosis and phagocytosis.
The antigen is transported across the M cells in vesicles and released at the basal surface. The antigen is then bound by dendritic cells, which activate T cells.
Describe some key features of organised lymphoid tissue in the gut.
It has a role in the initiation of the immune response.
There are a large number of B cell follicles.
It is directly exposed to microorganisms and particles within the gut (by M cells).
Isolated lymphoid follicles only contain B cells.
Both isolated lymphoid follicles and peyer's patches drain to mesenteric lymph nodes where the intestinal immune response is initiated.
What are defensins?
Antimicrobial peptides that change the charge on pathogens and kill them
Which intestine carries a higher bacterial load?
The large intestine
Describe how circulating leukocytes become activated in the gut.
The cells are circulating around the body and passing through all of the lymph nodes. When the cells pass through the gut, they express the CCR7 receptor (a chemokine receptor) and the L-selectin receptor. If they are activated as they circulate through the mesenteric lymph node, they lose the CCR7 receptor and become determined cells, rather than undetermined cells. They can no longer recirculate.
What happens to activated T and B cells?
They drain via mesenteric lymph nodes to the thoracic duct and return to the gut via the bloodstream. They express the adhesion molecule alpha4beta7, which attaches to MAdCAM-1 which is on the gut endothelium. The cells also express CCR9 which is attracted to CCL25 on small intestinal epithelium.
Which Igs do B cells mostly express?
IgA- 80 %
What other immunoglobulins do the B cells express? How much of each?
The reversal of the systemic humoral response
Where does IgA primarily exist in the gut?
In the mucous layer of the gut
What forms can IgA exist in?
As a monomer or a dimer
What is a J chain?
A joiner chain of two IgA molecules which form a dimer
What happens to an IgA after it has been produced by an IgA secreting cell?
A dimer binds to the poylmeric immunoglobulin receptor on the basal side of the epithelial cell. Once IgA has inhabited the receptor, the IgA and the receptor are endocytosed across the epithelial cell, and the IgA is released at the lumenar surface of the gut.
The secretory component is the part of the receptor which stays attached to the IgA dimer. It is incredibly important for the half life of the IgA as it covers the vulnerable hinge point of the IgA and prevents it from being digested.
What does IgA do in the lumen?
It can bind and neutralize pathogens in the mucous layer in the gut and peristalsis removes them.
It can also bind and neutralise antigens internalized in endosomes.
It can also export toxins and pathogens from the lamina propria.
What makes up most of the intraepithelial lymphocytes?
What appearance do they have?
90% T cells with80% being CD8+
They have an activated appearance, which means they are preactivated cells and contain full killing machinery.
What anchors the T cells in the epithelium?
The expression of alphaE:beta7 integrin
What are the two types of recognition mechanisms in the epithelium?
Virus specific recognition - TCR/CD8 cells. These kill va FAS receptor and ligand and initiate apoptosis
Stress specific recognition- stressed or damaged cells are recognised by NK cells.
Where specifically in the epithelium do the intraepithelial lymphocytes sit?
They sit between the epithelial cells, to control any damage on particular epithelial cells and to maintain membrane integrity.
How do the T cells kill pathogens?
By the direct release of perforins/granzymes on the cell they have targeted.
What are some proposed mechanisms for mucosal hyporesponsiveness?
Anergy or deletion of antigen specific T cells
Generation of regulatory T cells particularly CD4+ TGFbeta producing Th3 cells which control/dampen down the immune response
It is both immunosuppressive and induces switching of B cells to IgA production. IgA does not recruit neutrophils or cause an inflammatory response.
Commensal organisms also help regulate hyporesponsiveness.
How is the balance between protective immunity and homeostasis maintained?
A sophisticated means of discriminating between pathogen and innocuous substances has been developed. Inhibitory macrophages and tolerising dendritic cells prevent a response to an innocuous substance.
The default response to oral administration of proteins is that of a specific peripheral unresponsiveness- i.e oral tolerance
T cell and IgE mediated responses are inhibited more than IgG responses both locally and systemically