Lecture A1 - The Mucosal Surfaces and the Human Microbiota and Pathogens Flashcards
Name the three main mucosal surfaces of the human body?
Respiratory tract
Gastrointestinal tract
Urogenital tract
What is the first of the two contradictory functions of the major mucosa?
Facilitate exchanges between the inside of the body and the outside world.
Form an efficient barrier to microbes/pathogens.
What cells separate the inside from the outside of the body?
Epithelial
Describe simple squamous epithelial cells.
Lines blood vessels and air sacs of lungs.
Permits exchange of nutrients, wastes and gases.
Describe simple cuboidal epithelial cells.
Lines kidney tubules and glands.
Secretes and reabsorbs water and small molecules.
Describe simple columnar epithelial cells.
Lines most digestive organs.
Absorbs nutrients, produces mucus.
Describe stratified squamous epithelial cells.
Outer layer of skin, mouth, vagina.
Protects against abrasion, drying out, infection.
Describe stratified cuboidal epithelial cells.
Lines ducts of sweat glands.
Secretes water and ions.
Describe stratified columnar epithelial cells.
Lines epididymus, mammary glands, larynx.
Secretes mucus.
What is the second of the two contradictory functions of the major mucosa?
Hosts the largest fraction of the human microbiota.
Efficiently deal with pathogens.
Why are mucosal surfaces good sites for pathogens to invade and colonise?
They are in continuous, intense and dynamic contact with the outside world that allow for interactions with microorganisms.
What are the three levels of mucosal defences?
Immediate innate immunity.
Induced innate immunity.
Induced adaptive immunity.
Describe immediate innate immunity.
Epithelial cells - mechanical and chemical defences.
Microbial - microbiota direct and indirect and roles in defence.
Describe induced innate immunity.
Pathogens induced responses by epithelial cell, innate lymphoid cells, neutrophils and other immunocytes.
Describe induced adaptive immunity.
Pathogens cellular (ILC and T cell) and antibody-based responses (B cells).
What are the two barriers preventing crossings of infectious agents into the body?
High rate of tissue regeneration so epithelial cells always shedding releasing infected cells.
Muscle contractions that induce mucus movements that eliminate pathogens.
What is eubiotic microbiota?
Optimal functional configurations promoting health.
What is dysbiotic microbiota?
Pathological functional configurations promoting disease.
What are the indirect mechanisms of barrier functions mediated by the microbiota?
Stimulate activity and production of mucus.
Stimulates IL-1b processing and secretion.
Indirect induction of AMP released by epithelial cells.
Direct stimulation of antimicrobial production.
T-cell differentiation.
Induction of B cells and regulating the secretion of SIgA.
What are the direct mechanisms of barrier functions mediated by the microbiota?
Secrete antimicrobial molecules (peptide or hydrogen peroxide).
Limit the source of carbon.
Limit micronutrients.
Expression of virulence factors.
What are the 4 layers of the gut microbiota?
Mucosal microbiota.
Outer mucus layer.
Inner mucus layer.
Epithelial layer.
What are goblet cells and what do they produce?
Specialised epithelial cells.
Secrete gel-forming mucins, trefoil peptides and RELM-beta.
What are paneth cells and what do they produce?
Specialised epithelial cells.
Secrete AMPs, lectins and cytokines.
What are tuft cells and what do they do?
Specialised epithelial cells.
Sense parasites/microbes, induce type 2 cellular responses and activate goblet cells.
What do mucosal immunocytes do?
Regulate secretory cells differentiation and activities, produce polymeric IgA/IgM and modulate epithelial cell secretory function.
What are lysozymes and what do they do?
An enzyme.
Targets bacterial peptidoglycan.
What can AMPs and lectins do?
Target membranes.
AMPs can kill by disrupting cell walls or membranes and can also affect some viruses with lipid envelopes.
What are the 3 key intestinal AMPs?
Defensins
Lecticidins
Cathelcidins
What are the 6 major differentiated epithelial cell types in the human gut?
Tuft cells - sensory
Goblet cells - mucus secreting cells
Enteroendocrine cells - secrete hormones
Absorptive cells - bring in nutrients
M cells - catch bacteria from the luminal surface
Paneth cells - defensins
What are the mucus producing cells in the stomach?
Foveolar cells (mucin MUC5AC)
What are the mucus producing cells for the rest of the GI tract (not stomach)?
Goblet cells (mucin MUC2).
Why does the stomach have 2 mucus layers?
Inner and outer to keep away the highly acidic gastric juice.
When people have ulcers this means these layers are compromised.
What are mucins?
Highly glycosylated secreted and membrane bound proteins.
What are secreted mucins?
MUC2 - gel forming, goblet cells.
What are cell surface mucins?
MUC1 - most gut epithelial cells.
What forms the glycocalix?
Glycoproteins and glycolipids.
What is the glycocalix?
Protects cells against chemical, physical and biological damages.
GI tract has a thick glycocalix.
What do tuft cells do?
Snese parasites to regulate innate responses (entry route for noroviruses).
What do M-cells do?
Sample antigens from the lumen of the gut to initiate adaptive immune responses (entry route for some pathogens).
Name the 5 ways the mucosal immune response differs from its systemic counterpart.
Specialised sensing and antigen sampling strategies.
Distinct homing programme to allow immune effector cells to return across mucosal sites.
Specialised innate and adaptive immune effectors.
Suppressive mechanisms.
Mucosa associated microbiota required.
What are the 3 types of human pathogens?
Primary/overt pathogens
Opportunistic pathogens
Human specific versus zoonotic pathogens.
What are the 3 direct mechanisms of tissue damage by pathogens?
Exotoxin production
Endotoxins
Direct cytopathic effect
What are the 3 indirect mechanisms of tissue damage by pathogens?
Immune complexes
Anti-host antibody
Cell-mediated immunity
What are the 3 major ILCs?
ILC1 - intracellular immunity (activation of macrophages).
ILC2 - mucosal and barrier immunity (recruitment of eosinophils, basophils and mast cells).
ILC3 - extracellular immunity (recruitment and activation of neutrophils).
What is the distribution of the different ILCs across barrier surfaces?
Skin - ILC1 = 60.5%, ILC2 = 30.4%, ILC3 = 9.1%.
Lung - ILC1 = 7.7%, ILC2 = 88.8%, ILC3 = 3.5%.
Gut - ILC1 = 4.9%, ILC2 = 30.9%, ILC3 = 64.2%.
What are the 3 major immunological effector modules and their innate immunocytes?
Module 1 = macrophages.
Module 2 = eosinophils, basophils and mast cells.
Module 3 = neutrophils.
What are NETs?
Neutrophil extracellular traps.
Capture microorganisms for subsequent phagocytosis by macrophages or other neutrophils. A short lived suicide squad (netosis).
NETs are bits of DNA being secreted outside the cell to trap the microorganism.
How can microorganisms make it hard for NETs to capture them?
Can change their surface of their cells to make it difficult for the DNA net to bind to them.
Nucleases are produced to cut up the DNA net.
