gut immunology Flashcards
what does it mean that the gut is in a state of restrained activatiom?
dual immunological role between tolerance and active immune response
what are the major phyla of gut bacteria?
bacteriodetes
firmicutes
actinobacteria
proteobacteria
host factors influencing bacterial cell numbers
nutrients (bacterial growth)
digestive factors, peristalsis, defecation (elimination of bacteria)
where is gut bacteria most prevalent and why?
colon
no digestive factors so numbers highest here, increases along tract
what is dysbiosis?
microbial imbalance (pathobionts and symbionts)
causes of dysbiosis?
infection and inflammation diet xenobiotics hygiene genetics
types of anatomical mucosal defences in GI tract
Epithelial barrier
Peristalsis
factors produced by pathobionts contributing to disease development
TMAO
4-EPS
SCFAs
AHR ligands
what is the bacterial factor TMAO indicated in?
increased cholesterol deposition so athersclerosis
what are the chemical mucosal defences against pathogens in GI tract
Enzymes
Acidic pH
how do commensal bacteria form a mucosal defence?
occupy an ecological niche
act as second line to anatomical/chemical defences
what are the immunological mucosal defences of GI tract?
MALT (Mucosa Associated Lymphoid Tissue)
GALT (Gut Associated Lymphoid Tissue)
how does the epithelial barrier protect against infection?
mucus layer produced by goblet cells
tight junctions between epithelium
paneth cells (small intestine)
what is the role of paneth cells and their location?
small intestine, bases of crypts of Lieberkuhn
secrete antimicrobial peptides and lysozyme
what are MALTs?
mucosa associated lymphoid tissue esp in oral cavity
structure and location of MALTs?
below epithelium as a mass of lymphoid follicles
surrounded by high endothelial venules allowing easy passage of lymphocytes
oral cavity; linguinal tonsils, palatine tonsils, adenoid tonsils
what are GALTs?
gut associated lymphoid tissue
responsible for GI tract adaptive and innate response - B&T cells, macrophages, DCs, specific epithelial and intra-epithelial lymphocytes
what are organised GALTs?
peyers patches - distal ileum
caecal patches- large intestine
isolated lymphoid follicles
mesenteric lymph nodes
location of peyers patches?
distal ileum
what are non-organised GALTs?
intraepithelial lymphocytes
lamina propria lymphocytes
what are the nonorganised GALTs of small intestine?
intraepithelial lymphocytes - antimicrobial peptides
goblet cells
paneth cells
lamina propria
what are the non organised GALTs of large intestine?
goblet cells
intraepithelial lymphocytes
no paneth cells like small i
describe structure of peyers patches
aggregated lymphoid follicles underneath FAE (follicle associated epithelium) and M cells
sub epithelial dome of dendritic cells
B cells in follicle
naive t cells surround B cells
what are M cells in peyers patches?
microfold cells
antigen uptake through them via IgA receptors
allow IgA-bacteria complexes to enter peyers patches
what are follicle associated epithelial cells?
cells overlying peyers patches
have no microvilli, goblet cells or IgA
how can antigen sampling occur in the GI tract
via M cells
OR independent of M cells by transepithelial dendritic cells
how do transepithelial dendritic cells sample antigens?
can open tight junction proteins and send dendrites to lumen of gut
directly samples the bacteria and can transfer to mesenteric lymph nodes
describe the B cell adaptive response in the gut/GALT
mature (but naive) B cells express IgM
on antigen presentation, class switch to IgA
T cells and epithelial cells produce cytokines to influence maturation
B cells then mature to be IgA producing plasma cells
plasma cells then migrate and populate lamina propria
how does secretory IgA help immunological defence of gut
sIgA binds to luminal antigen, prevents adhesion and consequent invasion
how can circulating lymphocyte reenter intestinal GALTs?
process of lymphocyte homing
where do GALT lymphocytes travel after activation?
mesenteric lymph nodes
to enter thoracic duct, enter broad circulation
from there return to lamina propria (via lymphocyte homing)
or move to peripheral lymph tissue
what is peripheral lymph tissue?
skin
tonsils
BALTs - bronchus associated lymphoid tissue
what is the process of lymphocyte homing?
lymphocytes in HEVs
MAdCAM-1 on HEVs binds to lymphocyte 𝝰4β7 Integrin
lymphocytes roll until tethered by MAdCAM-1 for activation and rolling arrest
move through walls to lamina propria
why is there rapid turnover of enterocytes?
first line of defence - may be directly affected by toxic substances in diet
therefore any agents affecting cell function die off and effect is diminished
therefore any lesions will be short lived and not have long lasting effects
what bacteria is cholera caused by incl serotype
vibrio cholerae O1 and O139
MOA of cholera infection
Bacteria reaches small intestine → contact with epithelium & releasescholera enterotoxin
enterotoxin internalised via retrograde endocytosis
causes activation of adenylate cyclase to increase cAMP
causes active secretion of salt and fluid (via CFTR)
leads to watery diarrhoea via osmosis
transmission of cholera
faecal oral route - contaminated food and water
symptoms of cholera
severe dehydration and watery diarrhoea
vomiting
nausea
abdo pain
how to diagnose cholera
bacterial culture of stool sample
rapid dipstick also available
what protections are there against cholera
vaccine - oral inactivated (Dukoral)
what viruses cause gastroenteritis
rotavirus in children
noravirus
rotavirus treatment (gastroenteritis)
oral rehydration therapy
what are rotaviruses
RNA viruses
replicate in enterocytes
subtypes A-E
live attenuated vaccine against type A (most common)
what are noroviruses
RNA viruses
faecal oral transmission
usually outbreak in closed communities (cruises)
cause acute gastroenteritis symptoms - recovery 1-3 days
what is the treatment for norovirus gastroenteritis
none required
what is campylobacter gastroenteritis
commonest UK cause of food poisoning
low dose required for illness
treatment typically not required
which pathogens causing gastroenteritis typically require no treatment?
campylobacter
norovirus
some e coli
clostridium difficle gastroenteritis facts
often due to long term antibiotics
very contagious - isolate patient
start metronidazole/vancomycin
treatments for clostridium difficile
metronidazole or vancomycin
stop current antibiotics
can give faecal microbiota transplantation
pathotypes of e coli causing diarrhoea
enterotoxigenic enterohaemorrhagic enteroinvasive enteropathogenic enteroaggregative diffusely adherent
transmission of campylobacter
undercooked meat esp poultry
untreated water
unpasteurised milk
