Immunology of gut Flashcards
what is the surface area of the gi tract
200m^2
what is the antigen load in gi tract
resident microbiota 10^14 bacteria
dietary antigens
exposure to pathogens
what is meant by state of ‘restrained activation’ in gi tract
has to balance tolerance with active immune response
tolerate: food antigens and commensal bacteria
immunoreactivity against: pathogens
what is the gut microbiota
considered a virtual organ
4 major phyla of bacteria - bacteroidetes, firmicutes, actinobacteria, proteobacteria, also viruses and fungi
provide traits we have not had to evolve on our own
what is dysbiosis
altered microbiota composition
what are some causes of dysbiosis
infection and inflammation diet xenobiotics hygiene genetics
what are the physical barriers against pathogens
mucosal defence
anatomical - epithelial barriers and peristalsis
chemical - enzymes and ph
how does the epithelial barrier defend against pathogens
mucus layer - goblet cells
epithelial monolayer - tight junctions
paneth cell(small intestine) in bases of crypts of lieberkuhn
- secrete antimicrobial peptides and lysozyme
what is commensal bacteria
occupy ecological niche and act as barrier itself
what are some immunological defenses following invasion
malt - mucosa associated lymphoid tissue
galt - gut associated lymphoid tissue
what is malt
- found in submucosa below epithelium as lymphoid mass containing lymphoid follicles
- follicles are surrounded by HEV postcapillary venules - allowing easy passage of lymphocytes
what is galt
responsible for both adaptive and innate immune response through generations of lymphoid cells and antibodies
what are some examples of non organised galt
intra epithelial lymphocytes
lamina propria lymphocytes
what are some examples of organised galt
peyers patches(si)
caecal patches(li)
isolated lymphoid tissues
mesenteric lymph nodes - encapsulated
what are peyers patches
‘immune sensors’
found in submucosa of small intestine - mainly distal ileum
- aggregated lymphoid follicles covered with follicle associated epithelium
fae - no goblet cells, no secretory igA and lack microvilli
what is found in peyers patches
collection of naive t cells and b cells
- development requires exposure to bacterial microbiota
- 50 in last trimester foetus and 250 by teens
how does antigen uptake via peyers patches take place
via microfold cells within FAE
M cells express igA receptors - facilitating transfer of igA bacteria complex into peyers patches
what is the b cell adaptive response
mature naive b cell expresses igM in PPs
on antigen presentation class switches to igA
- t cells and epithelial cells influence b cell maturation via cytokine production
b cells further mature to become igA secreting plasma cells
populate lamina propria
what immunoglobulin do upto 90% of gut b cells secrete
igA
secretory IgA binds luminal antigen - preventing its adhesion and consequent invasion
why do enterocytes and goblet cells have short life span
can be directly affected by toxic substances in diet
- lesions will be short lived as responded to
what is the mechanism of cholera
acute bacterial disease caused by vibrio cholerae serogroups o1 and o139
- bacteria reaches small intestine - contact with epithelium and releases cholera enterotoxin
how is cholera transmitted
through faecal oral route
spreads via contaminated water and food
what are the main symptoms of cholera
severe dehydration and watery diarrhoea
other symptoms: vomitting, nausea and abdo pain
what is the diagnosis for cholera
bacterial culture from stool sample on selective agar is gold standard, rapid dipstick tests also available
what is the treatment for cholera
oral rehydration is main management - upto 80% cases can be successfully treated
vaccine - dukoral, oral and inactivated
globally : 1.3 - 4 mill cases
what are some viral causes of diarrhoea
rotavirus
norovirus - winter vomiting bug
what are some bacterial causes of diarrhoea
campylobacter jejuni escherichia coli salmonella shigella c. diff
what are some protozoal parasitic casues of diarrhoea
giardia lamlia
entamoeba histolytica
what are rota viruses
rna virus - replicates in enterocytes
5 types: A is most common in human infections
what is the treatment for rotaviruses
oral rehydration therapy
still causes ~ 200000 deaths/yr
vaccine - live attentuated oral vaccine against ype a
what is the norovirus
rna virus
incubation period 24-48 hrs
how is norovirus transmitted
faecal oral transmission
individuals may shed infectious virus for upto 2 wks
outbreaks often occur in closed communties
what are the symptoms of norovirus
acute gastroenteritis
how to diagnose norovirus
sample pcr
what are the most common species of campylobacter
c. jejuni and c. coli
how is campylobacter spread
undercooked meat esp pultry
untreated water
unpasteurised milk
low infective dose
what is treatment for camylobacter
non required usually
azithromycin
resitance to fluoroquinolones is problematic
what is e coli
diverse group of gram neg intestinal bacteria
most harmles
6 pathotypes associated with diarrhoea
what is the management for c diff
isolate patient
stop current antibiotics
give metronidazole and vancomycin
recurrence rate 15-35%, increasingly hard to treat
faecal microbiota transplantation - 98% cure rate
