Lecture 6- Human Microbiome III Flashcards
(26 cards)
Immune system basics
Two types;
*innate= non-specific
*adaptive= specific
Innate immune system
*physical barriers; skin, organ and mucosal layers
*chemical barriers; stomach acid, lysozyme in the eye
*innate response; inflammatory response cells; mast cells, neutrophils, macrophages + NK cells
- no memory
- fast response
- cells are non-specific
Adaptive system
- slower
- macrophage engulfs bacteria + presents its antigen to helper T + cytotoxic T cells
*CT cells= kill organisms
*helper T cells recruit B cells= replicate and generate antibodies
*those tagged with antibodies= set for destruction - antibodies = immunoglobulins
- cytokines can be released which impact on host cells
Immune system interactions
-evolved with resident skin microbes
-skin microbiota, epithelial cells + innate and adaptive arms of the immune system communicate
*keratinocytes = communicate by sensing microorganisms; pattern recognition receptors-identify pathogen-associated molecular patterns
Immune system interactions
-binding of PAMPs to PRRs triggers innate immune responses
*secretion of antimicrobial peptides
*kill fungi, bacteria + parasites
-some antimicrobial peptides= controlled by members of the skin microbiota
Skin
-focuses on staphylococcus aureus
Antibiotics produced by staphylococcus sp = prevent aureus colonization
*S epidermidis= inhibits S aureus biofilm formation
*production of the serine protease glutamyl endopeptidase (ESP)
- induce antimicrobial peptide production by skin cell = kill S.aureus
Skin pathogens
*S.hominis= produces lantibiotics- combine with human antimicrobial peptides to decrease S.aureus colonisation
*Propionbacterium acnes= enhance S.aureus biofilm formation through production of coproporphyrin III
Heart disease
*CAD= chronic inflammatory disorder- narrowing of the coronary artery due to plaque formation
^= blocking/reducing oxygen rich blood supply to the heart- may lead to heart attack
*microbiome analysis = presence of oral bacteria in atherosclerotic plaque samples
Role of oral microbes
-secrete proteins, peptides and proteases
-altering the host actin cytoskeleton in the gingival epithelium = causes inflammation
-allows bacteria to enter the bloodstream
-numerous types of oral bacteria form biofilms within atherosclerotic plaques = causes CAD
Immune response
-secreted proteins activate the immune system = causing inflammation
-cytokines-mediated = associated with CAD
-proteases = activate the complement system generating an inflammatory response
Oral microbiota CAD links
-organisms= secrete proteins, peptides + proteases found in the gingival crevice
^ leads to oral microbial entry to the bloodstream
Urinary genital tract
-key area for transmission of a number of diseases
-normal microflora
-female menstrual cycle has an impact
Vagina
-vagina colonised soon after birth with corynebacteria, staphylococci etc
-during reproductive life= vaginal epithelium contains glycogen due to the actions of circulating estrogens
*lactic acid bacteria predominates= able to metabolise the glycogen to lactic acid
*lactic acid= inhibit colonisation by none lactic acid bacteria
Preterm birth
-delivery before 37 weeks of gestation
^Common cause of neonatal morbidity
-half of PTB linked to changes in vaginal microbiota
-Normal pregnancy involves changes in inflammatory response in each
trimester with proinflammatory in first and third trimester and anti-inflammatory in second
Preterm vs full term
-changes in vaginal microbiota associated with ptb
-^due to microorganisms travelling from vagina to uterus
-more likely to have increased abundance of; sneathia amnii, prevotella, lachnospiraceae + saccharibacteria; associated with low levels of vitamin D
The GI microbiome + health
-highly diverse environment + normal flora
-microbiota play important roles in health
Short chain fatty acids
-short chain fatty acids are products of fermentation of dietary fibre in the GI tract; acetate, propionate + butyrate
-do not possess the enzymes necessary to produce SCFAs from fibre
-loss of SCFA- producing bacteria linked to T1D, T2D, liver cirrhosis, IBD + atherosclerosis
IBD
-complex chronic conditions
-heterogeneity in treatment response
-microbiome implicated in disease outcomes; multiple factors + faecal transplants attempted
IBD
-nearly all microbiome properties change in either activity/stability during disease
-large shifts in microbiota over a few weeks in pts with IBD
Outcomes;
-microbiome reverted to a baseline composition when the disease is not active
-patients had microbiome + immune responses that were less stable than others
-shifts in microbiome signalled changes in symptoms; both negative and positive
Key indicators
*Metabolic- octanoyl, carnitine, some lipids + short chains fatty acids
*Bacterial taxa- faecalibacterium, subdoligranulum, roseburia, alistipes + escherichia ; metagenomic + metatranscriptomic levels
*Regulators of interleukins
Gut/brain protection
*meninges= 3 membranes that protect the brain and spinal cord
-range of immune cells are found in the meninges
*plasma B cells= produce antibodies in response to infections
*meningeal plasma B cells= produce IgA (associated with the gut) also positioned next to important blood vessels
*meningeal IgA= originated in the intestine and migrated to the meninges = removal of these cells allowed infection to spread to the brain from the blood
The gut brain axis links to disease
Numerous PRRs activate the inflammasome (inflammation pathways)
-some depressive disorders link to this
*inhibition of capase-1 attenuates inflammation + anxiety like behaviours and modulates the composition of gut microbiota
Liver dysfunction
-influences immunity + metabolism of gut + a range of organs
-brain malfunction due to *hepatic encephalopathy + kidney disorders= observed in patients with liver ailments
-impaired brain function= seen in patients with advanced liver diseases
-decreased metabolism of ammonia associated with liver failure also associated with HE
-CVD of the heart + blood vessels = associated with fatty liver + other liver disorders
Gut-liver axis
*dysbiosis= increases gut permeability = microbial metabolites reach the liver
-affect hepatic immunity + inflammation
- immune cells activated by these metabolites = reach liver through lymphatic circulation
- liver= influences immunity and metabolism in multiple organs
-released bile acids + other metabolites into biliary tract= can enter the systemic circulation
