Lecture 1 Flashcards
Name the three major tracts covered by mucosal surfaces.
Gastrointestinal (GI) tract- mouth down to anus. Urogenital tract (genital and urinary organs) Respiratory tract (upper and lower)
What defines mucosal surfaces?
Presence of epithelial cells secreting mucus.
What is the name of the human and microbiota together?
Supraorganism
What types of environmental impacts can affect microbiota configuration, leading to either eubiosis or dysbiosis?
Antibiotics
Other parasites/pathogens
Diet
How many cells are there within each part of the supra organism?
100 trillion microbiota cells
10 trillion our own cells
What 2 ways do microbes impact our bodies?
They release bad things such as toxins.
Or good things such as metabolites (SCFAs, vitamin K)
Give an example of how dysbiosis occurs through environmental pressure.
Antibiotics will reduce biodiversity, biomass and increase pathobionts such as C. difficile because it has less competition so it can thrive.
What makes up the microbiome?
Viruses, bacteria, microbial eukaryotes and fungi.
What are examples of pathogens interacting with each other?
Herpes simplex virus allows bacterial resistance
General virulence susceptibility due to bacterial presence.
Helminths cause autoimmune disease resistance
E. coli and entamoeba hystolitica increase virulence of eukaryotes.
What are the two functions of mucosal surfaces?
Exchange with outside, eg breathing., feeding/digestion, reproduction.
Forms barriers to chemical or biological insults
What helps to modulate the two functions of mucosal surfaces?
Epithelial cells and microbiota, the microbiota can affect exchange rates.
What are the primary mucosal defence systems?
Immediate innate defences:
Mechanical- tight junctions between epithelial cells.
Chemical- AMPS, lactoferrin, lysozymes, mucus.
Microbial- Microbiota producing h2o2, lactic acid, bacteriocins. Microbiota acting as mutualists competing for nutrients and attachment sites.
How do microbial defences work?
h2o2 provides protection from candida.
lactic acid protects us from viruses such as hiv.
What is the secondary defence?
Induced innate immunity- (after infection).
More AMPs, macrophages and Mucins.
What is the tertiary defence system?
Adaptive immunity- Immunoglobulins (SIgA) and cellular responses.
What do lysozymes target?
The walls of bacteria- peptidoglycan
What type of bacteria produce h2o2?
Lactobacillus is an example.
What are pathobionts?
members of the microbiota that have the potential to cause pathologies.
what is a treatment for C. diff that is antibiotic resistant?
Faecal transplant, its extremely effective, donor is usually a family member
what needs to be done before a fecal transplant?
donor must be screened for pathogens.
what effect does a healthy microbiota have on T cells?
it decreases the Th2 IgE response, and promotes Treg levels which is important to decrease inflammation at mucosal surfaces.
what are the 2 major types of epithelial tissues on mucosal surfaces?
Stratified epithelium- multiple layers of epithelial cells (present in the oral mucosa and vagina).
Simple epithelium- one layer of epithelial cells, present on digestive tract, respiratory tract and urogenital tract (urethra).
what is 16srRNA profiling?
a way of studying the composition of bacteria within the microbiome by using specific bacterial primers for 16s ribosome.
what happens in mouse models if you completely remove the microbiota?
the immune system completely fails.
what are the 5 ways that the microbiota confers health benefits to the host?
detoxification- changing toxins into harmless metabolites
biosynthesis- making vitamins, e.g vitamin k
immune maturation- induction of peyer’s patches, inducing mucosal T cells and IgA plasma cells.
metabolic- helps to digest dietary fibre.
protective- directly or indirectly.
What do goblet cells and paneth cells produce?
goblet cells- Mucins
paneth cells- AMPs, lectins, cytokines
What do goblet cells and paneth cells produce?
goblet cells- Mucins
paneth cells- AMPs, lectins, cytokines
what is the length of the mucus layer?
10-700um
describe the inner mucus layer
relatively sterile
rich in antimicrobial molecules
describe the outer mucus layer
non-sterile, degrading mucus, microbes utilise mucin carbohydrates for energy.
what are antimicrobial peptides?
peptides with selective microbicidal effects against bacteria, fungi and protists as well as viruses with a lipid envelope.
how do AMPs kill pathogens?
they become anchored into the membrane and form pores which is lethal- also happens to the microbiota if it gets too close to the endothelium.
what are mucus producing cells in the stomach called?
foveolar cells
what is the structure of Mucins?
long proteins with repetitive elements with sugars attached to them.
what are all epithelial cells derived from?
stem cells
what are the four types of intestinal epithelial cells?
goblet cells, paneth cells, enteroendocrine cells and absorptive epithelial cells.
what epithelial cell type can chron’s patients lose?
paneth cells
what are the two compartments of the mucosal immune system?
the epithelium and lamina propria
how are pathogens detected?
through pattern recognition receptors (PRRs) recognising pattern-associated molecular patterns (PAMPs).
which cells express PRRs?
dendritic cells, macrophages and epithelial cells
what are the 4 families of PRRs?
toll-like receptors (TLRs)
Nucleotide-binding oligomerisation domain-like receptors (NLR)
c-type lectin receptors (CLRs)
RIG-1 like receptors (RLR)
what are c-type lectin receptors?
transmembrane proteins localised at the plasma membrane.
they recognise glycans from the walls of fungi and some types of bacteria
what’s an example of a c-type lectin receptor?
dectin-1, which recognises B-1,3 glycans of the cell wall of various fungal species.
what are NLRs?
cytoplasmic sensors with multiple subfamilies
what are the 3 subfamilies of NLRs?
NLPRs- recognise bacterial, viral, parasitic and fungal PAMPs
AIM2- detects viral and bacterial DNA
NOD1 and NOD2- recognise bacterial peptidoglycan.
what are toll-like receptors?
transmembrane proteins localised either at the plasma membrane or in endosomes.
they recognise proteins, nucleic acids, glycans
what pathways do TLRs activate?
MAP kinase, NFkB and IRF
what is an example of a tlr?
TLR4 recognises LPS, a component of the gram-negative cell wall.
What are RIG-1 like receptors?
cytoplasmic sensors of viral RNA
trigger antiviral responses including the production of type 1 IFN
what do RIG1 receptors signal via?
mitochondrial adaptor proteins (MAVs)
What are examples of RLRs?
RIG-1 and MDA5
How does the mucosal adaptive immune system response differ to its systemic counterpart?
It has specialised antigen sampling strategies
has distinct homing programme which allows immune effector cells to return to mucosal sites
specialised immune effectors including the secretary IgA (sIgA)
a variety of suppressive mechanisms
why does the mucosal adaptive immune system response have a variety of suppressive mechanisms?
to maintain tolerance to environmental antigens (food)
to avoid inflammations against mucosal microbiota
what are primary pathogens?
cause disease upon infection, usually not present in the host population
what are opportunistic pathogens?
cause disease under circumstances, typically thrive in immuno-comprimised hosts, and can cause great damage.
