Transcript Innate immunity in the large intestine

CATEGORY: ORGANS & TISSUES
INNATE IMMUNITY IN THE LARGE INTESTINE
Innate immunity
in the large intestine
Matthew deSchoolmeester, University of Manchester, UK
Gut morphology and function
The surface of the intestine is highly folded, forming crypts and villi. Cells
move from the base to the tip of the crypt where they are lost into the lumen
by anoikis (a kind of apoptosis). The high turnover of epithelial cells can be
visualised via the incorporation of BrdU. It takes 5-7 days to travel from the
base to the tip (shown by the arrow). This process is accelerated by Th2
cytokines
such
as
IL-13.
The rate of epithelial cell turnover and also smooth muscle contraction
(peristalsis) often increase in response to infection. This is a physical way of
flushing pathogens out of the intestine.
Goblet cells and mucus
Goblet cells are simple columnar epithelial cells which develop
from stem cells in the base of the crypt. They contain
mucopolysaccharide in secretory granules which expands up to
500-fold after release. LPS from Gram-negative bacteria and
Th2 cytokines are goblet cell stimulants. They cause increased
expression
and
exocytosis
of
MUC5A
and
5B.
Mucus protects enterocytes by acting as a physical barrier to
the motility and feeding of bacteria and other pathogens such as
intestinal parasites. It also contains large quantities of IgA
capable of trapping invading bacteria.
L
Tm
Naive
Infected
L
Periodic acid Schiff stains goblet cells in the
large intestine pink, blue or purple
depending on their acidity. Infection with a
nematode parasite causes an increase in
goblet cell number. L; lumen, Tm; Trichuris
muris.
Continued next page…
© The copyright for this work resides with the author
The intestine is home to about 100 trillion (1x1014) bacteria, both commensal (“friendly”) and
pathogenic. To fight infection quickly the intestine has several innate immune defences designed
to act immediately when alerted to danger.
CATEGORY: ORGANS & TISSUES
INNATE IMMUNITY IN THE LARGE INTESTINE
Innate immunity
in the large intestine
cont.
Innate effector molecules
Produced by goblet and epithelial
cells as well as neutrophils and
macrophages in response to
numerous pathogens. These
molecules are not antigen specific
and do not exhibit immunological
memory.
Defensins
α- and β-defensins are produced in
the intestine and kill a wide spectrum
of pathogens in vitro. Low levels of βdefensin-2 are associated with an
increased risk of colonic Crohn’s
disease.
Cathelicidin
Only one identified in humans; LL37,
which is anti-microbial and binds and
neutralises LPS.
RELM-
A goblet cell molecule associated with
expulsion of the nematode parasite
Trichuris muris.
Innate Immune cells
The large intestine is also home to tissue-resident macrophages, eosinophils and mast cells.
Between them these cells can phagocytose pathogens and release toxic and inflammatory
mediators such as nitrogen radicals and histamine. Neutrophils are often the first cells recruited to
a site of inflammation and phagocytose and destroy pathogens using toxic enzymes such as
lysozyme and peroxidase.
Pathogen Recognition Receptors
These include the TLR and NOD families of receptors. Normally expressed on the basal side of the
epithelial layer or even intracellularly to avoid activation by the normal flora, they are ideally placed
to alert the immune system to the presence of invading pathogens. Detection of pathogenassociated molecular patterns by these receptors initiates a powerful inflammatory response.