alimentary immune functions Flashcards
immunology: recall the main immunological processes associated with Peyer's patches & gut immunology, including the role of M-cells and dendritic cells, and the purpose of lymphocyte homing and circulation
why is the epithelium of the digestive tract an external environment
possible for bacteria to reach without crossing a membrane
distribution of microbiota in alimentary tract (mouth; stomach; duodenum, jejunum, ileum; caecum, colon)
mouth: lots as put in lots of dirty things; stomach: not many as low pH; duodenum, jejunum, ileum: low due to paneth cells and Peyer’s patches; caecum, colon: huge increase)
4 main mechanisms of protection against infection in gastrointestinal mucosa
physical barriers, chemical barriers, bacteria protection, immunological
5 physical barrier mechanisms
tight epithelial wall, glycocalyx, mucous, unstirred layer, peristalsis
2 chemical barrier mechanisms
bacteriacidal enzymes from paneth cells, acid from stomach
bacteria protection mechanism
commensal bacteria maintain immune system priming and may attack foreign species
what is mucosa-associated lymphoid tissue (MALT) rich in
T and B cells
2 categories of mucosa-associated lymphoid tissue (MALT)
GALT (gut-associated lymphoid tissue), BALT (bronchus-associated lymphoid tissue)
how can GALT (gut-associated lymphoid tissue) be split into 2 categories
organisation (organised and disorganised)
what are examples of organised GALT (gut-associated lymphoid tissue)
Peyer’s patches in small intestine, lymphocytes in mesenteria lymph nodules (where lymph from villi drain)
what are examples of disorganised GALT (gut-associated lymphoid tissue)
lymphocytes in lamina propria (mainly IgA-secreting B-cells), lymphocytes in space below baseolateral membrane of epithelium (intra-epithelial cells)
what can also phagocytose bacteria in the liver
Kuppfer cells
what do Peyer’s patches consist of
aggregated lymphoid follicles covered with follicle associated epithelium (FAE)
where are Peyer’s patches found
small intestine (most abundant in distal ileum)
function of Peyer’s patches
immune sensors as capable of monitoring local bacteria; provide protection against pathogenic bacteria
what is the development of Peyer’s patches dependent on
exposure to bacterial flora
numbers of Peyer’s patches by last trimester and maximum in teenage years
50, 250
what are Peyer’s patches rich in
B cells, T cells, macrophages, dendritic cells
what does follicle associated epithelium (FAE) overyling dome structure of Peyer’s patches contain
M cells (specialised enterocytes without surface microvilli; instead contain microfold on apical membrane); has reduced number of goblet cells and enterocytes
main function of M cells
perform transcytosis of luminal bacteria, antigens and proteins
what is transcytosis
transcellular transport in which various macromolecules are captured by exocytosis, transported across the interior of a cell, and out the invaginated basolateral membrane via vesicles to infiltrating lymphocytes
why do M cells express IgA receptors
they facilitate transfer of IgA-bacteria complex into Peyer’s patches
what also assists in antigen uptake besides M cells
dendritic cells which capture particles for M cells (present in sub-epithelial dome along with naive B, T cells and macrophages)
fate of antigens
presented to lymphocytes in Peyer’s patches for assessment and potential immunological response
fate of activated lymphocytes
develop gut homin markers and migrate to mesenteric lymph nodes for proliferation
how is the apical membrane of M cells specialised for its function
no glycocalyx or membrane hydrolytic enzymes
what can M cells also produce
pro-inflammatory cytokine interleukin 1
fate of cells on villous side of crypt during embryonic and postnatal development
differentiate into absorptive enterocytes, goblet cells, enteroendocrine cells
fate of cells on FAE side of crypt during embryonic and postnatal development
differentiate into absorptive enterocytes, M cells, rarely goblet cells
susceptibility of M cells
suceptible to pathogens as ability to transcytose and accessible
what is the most abundant antubody in the body (not just circulating)
IgA
why is IgA the most abundant antibody
highly prevalent in mucosal secretions because MALT is associated with large numbers of IgA+ B cells
structure of secretory IgA (SIgA)
dimeric form of IgA
where is SIgA produced and fate
by B cells in lamina propria and transported across enterocyte to be secreted into interstitial space
what binds both IgA molecyles together in plasma (B) cells
J-chain
what does the IgA dimer bind to
special receptor on external basolateral surface of enterocytes (polymeric immunoglobulin receptor, pIgR)
what does the pIgR (receptor) become and subsequently bind to to form SIgA
becomes secretory component and binds to length of IgA dimer, becoming SIgA
fate of SIgA
endocytosed into the epithelial cell, actively transported within vesicle to apical membrane, exocytosed into gut lumen
what are the functions of the secretory component
help IgA move through enterocyte, protect antibody dimer from enzymatic and acidic degradation
when SIgA bind to pathogens, what do they prevent
pathogens adhering to mucosal wall
what is antigen-specific SIgA production stimulated by
M cells and dendritic cells in Peyer’s patches
fate of stimulated mucosal lymphocytes in Peyer’s patches
migrate into local mesenteric lymph nodes and drain into lymphatic system
how do lymphocytes reach systemic circulation before spreading throughout body in blood
via thoracic duct
what is lymphocyte homing
lymphocytes remaining in blood until activated by tissue-sepecific endothelial adhesion molecules at site of inflammation, allowing transmigration of lymphocytes into gut mucosa
what does lymphocyte homing require
specialised post-capillary microvascular endothelial cells, such as high endothelial venules (HEVs) of lymphoid tissue
what is constitutively expressed on surface of lymphocytes
L-selectin (carbohydrate-binding lectin)
function of L-selectin
mediates low adhesive interactions that enable leukocytes to roll in postcapillary venules and HEVs
how does L-selectin mediate lymphocyte rolling in HEVs
binds to mucosal addressin cell adhesion molecule-1 (MAdCAM-1)
where is MAdCAM-1 constitutively expressed
HEVs of Peyer’s patches and mesenteric lymph nodes; flattened endothelial cells localised in lamina propria of small and large intestine (enabling lymphocyte recruitment in chronic gut inflammation)
diagram of lymphocyte circulation
diagram
