Microbiota and the immune response Flashcards
what percentage of the cells in our body are microbial?
90%
where is most bacteria located
the large intestine
what can change the microbiome
stress, diet, antibiotics- imbalances can lead to inflammatory bowel disease, allergy and autoimmunity
benefits of microbials
required for development of the immune system, provide energy by metabolizing dietary polysaccharides, provide vitamins, protect from pathogenic bateria
commensal bacteria are
present at all mucosal surfaces and the composition is different at each site
germ free animals immune systems
have almost no secondary lymphoid tissues including mucosal tissues
Clostridium difficile
disease that occurs after treatment with antibiotics that kill the commensal bacteria in the gut
proof of probiotics protective effects
mice given an oral does of a commensal bacteria (Bacillus subtilis) were protected from E. coli.
How Can Commensals Protect from Intestinal Inflammation?
Balance pro and anti-inflammatory immune responses. Some bacteria promote TH cells; others promote Treg cells
Dysbiosis favors
pro-inflammatory (TH17 and TH1) over anti-inflammatory (Treg) state
Inflammatory Bowel Disease (IBD)
(Crohn’s disease and ulcerative colitis)
T cell-mediated inflammatory response due
to stimulation by microbial antigens
IBD likely due to changes in development or
composition of intestinal microbiota (dysbiosis)
Commensal bacteria thought to be initiating factor
can be transferred via fecal transplant
allergy is decreased in
Children growing up on farms
Children attending day care during 1st 6 months of life
East German children compared to children in more
developed West Germany
Allergy is increased in
children given antibiotics in the first year of life
Hygiene hypothesis
early childhood infections lead to protection from allergy later in life. early life exposure to some microbes can alter susceptibility to disease particularly allergy
what happens to antibiotic treated mice vs. normal mice exposed to dust mites
Antibiotic treated mice were more likely to develop allergies to dust mites
Balance Between TH1 and TH2 Cells
Bacteria and viruses elicit TH1 responses
(IL-2 and INFγ)
TH1 responses down regulate TH2 response
which produces IgE (allergy)
Insufficient TH1 response due to decreased
bacteria and viral infections would increase
TH2 response (IgE)
Autoimmunity and comensal bateria
intestinal bacteria were shown to protect mice from autoimmune disease by inducing anti-inflammatory Treg cells
TLR5-/- mice:
Have increased food intake, insulin resistance,
hypertension and are obese (metabolic syndrome)
Have altered gut microbiota (dysbiosis)
Antibiotic treatment reversed obesity
Fecal transplant of obese TLR5-/- mice into antibiotic treated normal mice caused obesity- suggests that microbiota can cause obesity
how does a high fat diet change microbiota
affects intestinal lymphoid cells to secrete IL-22 which induces expression of anti-microbial peptides altering microbiota and promoting obesity
Causes of Dysbiosis
- antibiotics
- Diet (especially high fat)/stress
- early childhood experiences- hygiene hypothesis
- Cesarean delivery
- genetics
C-section deliveries promote microbiota more similar to
mothers skin microbiota
gut microbiota affects on cancer therapy
when microbiota are decreased by antibiotics cancer therapy is not as affective
