infection and immunity Flashcards
4 methods of protection against infection
physical barrier
chemical barrier
bacteria protection
immunological
physical barrier
tight epi wall glycolyx mucous and unstirred layer peristalsis - keep things moving epi barrier - Paneth cells - secrete defensins and lysozyme
chemical barrier
bacteriacidal enzymes from Paneth cells
acid - stomach
bacterial protection
commensal bacteria maintain immune system priming
may attack foreign species
occupy niche
immunological
MALT - rich in T and B cells
GALT
BALT - bronchus
GALT
adaptive and innate
generate AB
peyer’s patches, caecal patches- lymphoid tissue - in SI
lymphocytes - mesenteria and lymph nodules (where the lymph from villi drain) and isolated lymphoid follicles
disorganised sites of lymphocytes in lamina propria and lymphocytes in interstitial space between basolateral membrane of epithelium - intra-epithelial cells eg T cells and NK cells
NOT GALT - kuppfer cells in liver - phagocytose
what is the GI immune system tolerant against
food antigens
commensal bacteria
what is essential for the gut immune system
the bacterial microbiota
describe the gut microbiota
more bacteria than the cells in our body
4 phyla
many more genes - provide us with the ability to digest
gut microbiota through the GI
stomach - pH = few bacteria
colon = exponential increase
number increased with ingested and secreted nutrients
decrease with peristalsis, contractions, defecation
symbiotic bacteria
take and provide nutrients and regulation
commensal bacteria
occupy a niche
prevent adhesion of pathogens
pathogens
cause inflammation
describe dysbiosis
regulation interrupted and inflammation occurs
causes of dysbiosis
infection diet xenobiotics hygiene genetics
diseases caused by dysbiosis
brain - stress, autism, MS
lung - asthma
liver - NAFLD, NASH
adipoise tissue - obesity, metabolic disease
intestine - IBD, coeliac
systemic disease - T1DM, atherosclerosis, rheumatoid arthritis
MALT
submucosa below epithelium
contain lymphoid follicles
follicles surrounded by HEV postcapillary venules = easy passage of lymphocytes
eg oral cavity
peyer’s patches
aggregated lymphoid follicles
covered by follicle associated epithelium
this has no goblet cells, secretory IgA or microvilli
have M cells
in SI - most in distal ileum
immune sensors - monitor local bacteria, protect against pathogenic bacteria
development needs exposure to bacterial flora
hit maximum 250 by teenage years
rich in B cells, T cells, macrophages and dendritic cells
M cells
the way that antigen uptake occurs in FAE
have IgA receptor
facilitate transfer IgA bacteria complex into Peyer’s patches
antigens presented to lymphocytes = activation
describe trans-epithelial dendritic trees
DC
perform antigen sampling
thin extension - bring back into organ
DC form TJ with epi - doesn’t allow entry of pathogens
describe the actiation of B cells
mature naïve B cells express IgM
when antigen presented to B cell - class switch to IgA
T cell and B cell influence maturation by cytokines
B cell mature to become mature IgA secreting plasma cells
populate the lamina propria
describe thymus dependant B cell maturation
B cell meets antigen
if correct antigen - T cell gives B CD40L
B cell is activated
describe the formation of secretory IgA
in submucoisa - dimeric IgA binds to poly-Ig receptor on basolateral membrane
taken into vesical
enzymatic cleavage
makes secretory IgA
action of sIgA
neutralisation
action of secretory component
protects against the gut
mucus in LI
there is a lot
doesn’t let bacteria in
describe lymphocyte homing
lymphocyte in circulation and secondary lymphoid tissue
if find correct antigen - most likely to go back to organ it found the antigen - thinsk more likely to meet more antigens
describe extravasation of lymphocytes
rolling fascilitated by weak binding of selectin
strong α4β7 integrin (on lymphocyte)/MAdCAM-1 (on epi) binding causes activation and arrest of lymphocyte - homing back to gut
mechanism of cholera infection
acute bacterial disease - vibro cholerae serogroups O1 and O139 - cholera toxin
gram -ve
comma shaped
bacteria reach SI
make close contact with epi - releases toxin
cause exit of Na K Cl and water = diarrhoea
transmission of cholera
faecal oral - contaminated water and food
symptoms of cholera
severe dehydration and diarrhoea
vomiting
nausea
abdominal pain
diagnosis of cholera
bacteria culture from stool sample on selective agar
rapid dipstick tests are also available
treatment of cholera
oral rehydration
vaccine - for travellers - Dukoral, oral, inactivated
viral infections causing diarrhoea
rotavirus
norovirus
bacterial causes of diarrhoea
campylobacter jejuni E coli salmonella shigella C difficiile
protozoal parasitic
giardia lambia
entamoeba histolytica
describe rotavirus
RNA
replicates in enterocytes
types A - E
A most common - human infections
most common cause diarrhoea in infants and young children ]
treatment - oral rehydration therapy
vaccination - live attenuated oral vaccine - rotarix against Type A
describe norovirus
RNA diagnosis - PCR symptoms - acute gastroenteritis recovery - 1-3 days transmission - faecal-oral route - up to 2wks outbreaks occur in closed communities
descrive campylobacter
transmission - undercooked meat, untreated water, unpasteurised milk - low infective dose
treatment - not necessary, azithromycin, fluroquinolones - resistance so means problematic
describe enterotoxigenic E coli
cholera like toxin
watery diarrhoea
describe entrovasive E coli
shigella like illness
bloody diarrhoea
describe enterohaemorrhagic or shiga toxin producing E coli
loss of kidney function
describe C difficile
normally in epi - do no harm
on AB microbiota killed
C difficile = pathogenic
destroy lining = leakage of neutroohil and RBC = bloody diarrhoea
treatment - stop current AB
treat with metronidazole, vancomycin
high recurrence - increasingly difficult to treat
can treat with faecal microbiota transplantation
describe coeliac disease
gliadin not broken down in stomach - reach SI - bidn to sIgA - transferred to lamina propria
innate immune detection -T cell developmet - T and B co-stim - cytokines, chemokines and their receptors
symptoms - abdominal distension, diarrhoea
diagnosis - Ab blood tests- anti-gliadin, biopsy of duodenum
treatment - gluten free diet
describe IBS
visceral hypersensitivity - triggered by diet and stress
symptoms - recurrent ab pain, abdominal bowel motility, constipation/diarrhoea
treatment - diet modiufication (avoid apples, beans cauliflowers, constipation - soluble fibre, stool softeneers, osmotic laxitives, spasms and pain - anti-diarrheals, anti-muscarinic
management of stress, anxiety and depression
describe crohn’s disease
distal ileum and colon
patches of inflammatory damage - cobblestone appearance
symptoms - diarrhoea, ab cramp, fever, anaemia, weight loss and fatigue
diagnosis - Ab blood tests, endoscopy and barium x-ray
treatment - anti-inf drugs, immunosuppressants, surgery - not curative
describe ulcerative colitis
colon only
continuous inflammation
bloody diarrhoea, ab cramp, anaemia, weight loss, fatigue
diagnosis - Ab blood tests, endoscopy and barium x-ray
treatment - treatment - anti-inf drugs, immunosuppressants, colorectomy - curative
mechanism of IBD (irritable bowel disease) ie Crohn’s and ulcerative colitis
2/3 genes identical lining destroyed bacteria entry stimulate immune celk regulation falls constant action chronic infection colon cancer
