Is lower or higher gastrointetsinal tract larger in density of microbes and complexity?
lower
1014 cells
1000 - 1150 different bacterial species
What does the microbiota consist of
bacterial
viruses
fungi
What are the task of the microbiome ?
food digestion
biosynthesis
protection
profound effect in shaping our immune system
What are the thress key immunological properties of the microbiota?
colonization resistance (direct and indirect)
regulation of adaptive immunity
immune system development
What are the 3 methods of direct colonization resistance?
Nutrient or space competition
Active antagonism (directly kill)
inhibitory metabolites (limit growth of pathogens)
What are the 3 methods od indirect colonization resistance?
mucus barrier function
fibre imrpoves mucous layer (food for microbiota)
mucosa can release fucose which supresses virulence of certain bactera
oxygen limitation
butyrate for example limit oxygen to pathogens
microbiota mediated immune responses
induce production of amp (antimicrobial peptides)
promote IL-22 critical protection
induce IgA & IgG
What do germ free mices lack of
unterentwickeltem Immunsystem,
wenig Th17-Zellen,
reduzierten IgA-Spiegeln,
dünner Schleimschicht und
kleineren Peyer’s patches & Lymphfollikeln.
susceptibility to allergies
Which influence does microbiota have in adaptive immune response
induction of IgA
differentiation into Th17 lineage
What are the two shield the pathogen needs to overcome before beeing affective?
overcome
microbiota and pyhsical barrier
evade the innate response
What are the 3 steps of innate immunity for intestinal pathogens
epithelial cell get induced to express inflammatory cytokines, chemokines and other mediators. These recruit&activate neutrophils, macrophages and dendritic cells
activation of inflammasome induces production of IL-18 (which activates myeloid cells and increases barrier integrity)
bacteria in cytoplasm or escaping from phagosome are taken into formin autophagosome and destroyed after fusion with lyosome
What is the first step by infection and which two sorts exist
attaching
invasive and non-invasive
What are pili/fimbriae, afimbrial adhesins, and type III & IV secretion systems — and what are their roles in bacterial infection?
Structure / System
Main Function
Mechanism / Example
Pili / Fimbriae
Adhesion to host cells
Hair-like surface structures anchoring bacteria to epithelia (e.g. E. coli, Neisseria)
Afimbrial adhesins
Direct binding to host receptors
Surface proteins (no pili) binding ECM or integrins (e.g. Yersinia YadA, E. coli Intimin)
Type III secretion system (T3SS)
Inject effector proteins into host cells
“Molecular syringe” — manipulates host signaling (e.g. Salmonella, Shigella, Yersinia)
Type IV secretion system (T4SS)
Transfer DNA/proteins into other cells
For conjugation or effector delivery (e.g. Helicobacter pylori, Legionella)
Is vibrio cholera invasive or non invasive? And how does it work?
non invasive
ingestion via contaminated food or water
trigger TCP & CT
CT B & A -> CTA leads to ion exchange imbalance and massive water loss
infection leads to long lasting immuntiy through protective IgA
Is EPEC invasive or non invasive? And how does it work?
efface the epithelial barrier by destroying the villi
causes acute colitis
1. attach through translocated intimin receptor
2. strong innate response
macrophages damage IEC & release IL 23 & IL1b which activate IL 22 which induce AMP release
3. following a strong type 3 adaptive response
Th17, IgG & neutrophils recruites to inflamed mucosa, resulting in increased IL-22
clearance
IgG & neutrophils
Is listeria monocytogenes invasive or not and which immune response is provoked?
invasive
strong type 1 & cytotoxic response
How does listeria monocytogenes function?
Uptake:
Mcells
goblet cells: InIA bind
interaline with hooks bind on E-cadherin
LLO (listeriolysin) breaks endosomes inside cytoplasm
polymerizes cell actin filaments -> propel them to membrane and can infect neighboring cells
Is salmonells invasive or not and which immune respond is triggered?
type 1, dominated by Th1
Which 3 ways of entry are there for salmonella and what drive Th17 response
enter and kill M cells -> infect macrophages and epithelial
ivade luminal surface of epithelial
enter phagocytic cells that are sampling the gut luminal contents
Th17 response driven mainly by flagellin antigens
Which two viruses you know for intestinal?
rotavirus
double stranded RNA virus
strong type I IFN response
IgA critical for clearance
norovirus
single stranded RNA virus
IgA & T cells critical for clearance
What is IBD stand for, what are the subcategoires and where to find them?
Inflammatory bowel disease
Chrons disease -> complete GI
Ulcerative Colitis -> Colon
What are factors for IBD
genetic factors
environdmental factors
lead to microbiota specific CD4 Tcells
dysbiosis
barrier dysfunvtion
What is happening longtime if you have celial disease
atrophy and destruction of villi
crypt hyperplasis
What happens in celiac disease and why are Th17 cells involved?
Gluten is broken into gliadin peptides.
Enzyme tTG changes (deamidates) them → they bind better to HLA-DQ2/DQ8 (MHC-II).
DCs present these peptides during inflammation → activate Th17 and Th1 cells.
Th17 cells make IL-17 → cause gut inflammation and tissue damage.
Result: epithelial destruction, villous atrophy, and malabsorption.
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