GI infection and immunology Flashcards
massive antigen load
resident microbiota, dietary antigens, exposure to pathogens
restrained activation
tolerance (food antigens; microbiota required for healthy imune system) vs active immune response (dual immunological role)
function of microbiota
depends on nutrients available to increase cell numbers; peristalsis, contrations, defecations and digestive factors reduce amount
dysbiosis of microbiota
symbionts (regulation), commensals, pathobionts (inflammation); can be unbalanced
causes and disease development
infection and inflammation, genetics, hygeine, xenobiotics, diet
dysbiosis
produce metabolites and toxins which can affect many tissues (brain, lung, liver, adipose, intestine) or whole body (systemic)
physical barriers
epithelial (goblet cells - tight junctions - paneth cells), peristalsis, enzymes, low pH
commensal bacteria
ecological niche
immunological following invasion
MALT, GALT
MALT
organised beneath epithelium as lymphoid mass containing follicles surrounded by HEV postcapillary venules (allow easy passage of lymphocytes); oral cavity rich in immunological tissue
GALT
adaptive and innate immune response; sections of unorganised and organised
non-organised GALT
intra-epithelial lymphocytes (T cells, NK cells); lamina propria lymphocytes
organised GALT
Peyer’s patches (small intestine), caecal patches (large intestine), isolated lymphoid follicles, mesenteric lymph nodes (encapsulated)
Peyer’s patches
immune sensors; found mainly distal ileum; aggregated lymphoid follicles covered with follicle associated epithelium (no microvilli, goblet cells, secretory IgA)
Peyer’s patches
organised collection of naive T and B cells, requiring exposure to bacterial microbiota to develop; M cells sample antigens in gut lumen (FAE) and uptake antigens to Peyer’s patch lymphocytes
M cells
express IgA receptors, facilitating transfer of IgA-bacteria complex into Peyer’s patches
trans-epithelial dendritic cells
perform antigen sampling from submucosa through thin extensions through tight junction proteins in mucosal epithelial cells without compromising epithelial barrier
B cell adaptive response
thymus-dependent B cell maturation
mature naive B cells express IgM in Peyer’s patches, but switch to IgA upon antigen presentation
T cells and epithelial cells influence B cell maturation via cytokine production, then further mature to become SIgA and populate lamina propria
SIgA formation
dimeric IgA in blood, poly-Ig receptor on epithelial cells, becomes SIgA (by neutralisation)
large intesine
not as deep crypts; outer and inner mucous layer (outer so thick pathogen can’t enter)
lymphocyte homing and circulation
activated lymphocytes to mesenteric lymph node (proliferation) to thoracic duct and circulation; either back to lamina propria (most) or other lymphoid organs
entering lamina propria
integrin/MAdCAM-1 adhesion (homing) - strong binding leads to activation and arrest
vaccine cholera
dukoral, oral, inactivated
causes of infectious diarrhoea
viral, bacterial, protozoal parasitic
viral infectious diarrhoea
rotavirus: (RNA, A most common), oral rehydration, vaccine (rotarix); norovirus (norwalk virus): RNA, sample PCR, acute gastroenteritis, faecal-oral
bacterial infectious diarrhoea
campylobacter (curved): undercooked meat, untreated water, low infective dose can cause disease, no treatment normally required but can use antibiotics (azithromycin); E. coli: 6 pathogenic strains; cholera like toxin with watery diarrhoea; cause haemolyric uraemia syndrome (bloody diarrhoea); shigella like illness; C. difficile: antibiotics cause dysbiosis (disbalance) and cause C. difficile to propogate and cause bloody diarrhoea; isolate patient, stop current antibiotics, replace with others, if becomes increasingly difficult to treat use faecal microbiota transplantation