Barrier Immunity Flashcards
what do barrier organs protect?
the internal surfaces
what are the immune systems associated with mucosal tissues (MALT)?
- gut = GALT
- respiratory tract (includes the nasal and bronchial tract)
what are the physical mechanisms of mucosal protection?
- one or more layers of epithelial cells
- mucus layer
- pH and osmotic control
- cilia
- antimicrobial peptides
- sensor cells/ tuft cells
what are the two main goals of GALT?
to clear pathogens and maintain homeostasis
what is GALT tolerance promoted by?
oral tolerance and bystander suppression
organs that have GALT:
tonsils
adenoids
peyer’s patches
esophagus
appendix
what else does the epithelial layer do, than just provide a physical barrier?
sends signals to the underlying immune system, alarmins
what are the two types of signals that trigger the immune system?
- PAMPS (pathogen associated molecular patterns)
- DAMPS (damage-associated molecular patterns)
what are some examples of DAMPS?
alarmins, pH, salt, CO2, etc
what pathogens are responsible for type 1 immunity?
- viruses
- bacteria
- fungi
- protozoa
what pathogens are responsible for type 2 immunity?
- helminth
- allergens
- venoms
what molecules do the microbiota produce that are recognized by the immune system?
- short chain fatty acids
- vitamins
- histamine
- glycoproteins
- microbial peptides
what are the key differences that determine the balance of inflammation and homeostasis?
- TGFbeta
- IL-10
- IFNy
-IL-17
-TNFalpha
important points to remember:
- barrier organs are an immunological battlefield
- communication between epithelial and immune cells is critical
- mucosal immune systems are composed of secondary, tertiary lymphoid organs as well as tissue
- the microbiome contributes to the immune response and tissue homeostasis
- key cytokines determine the balance between homeostasis (TGFbeta, IL-10) and inflammatory responses (IL17, TNFalpha, IFNy)
what are the distinct sections that the gut is organized in?
stomach, small intestine, large intestine
what is the pH a strong determinant of?
the species of bacteria we can find in each section
where is microbial abundance the highest?
further down the intestinal tract, i.e., the large intestine
what are the gut epithelial cells and what is their function?
- enterocytes: absorption
- goblet cells: mucus production
- microfold cells: transcytosis of antigen
- paneth cells: secretion (AMPS)
- Tuft cells: sensor cells
- Intraepithelial lymphocytes: rapid antigen-specific responses
what are the first lines of defense
- mucus barrier
- epithelial barrier
- IgA secretion
what are IgA? what do they do?
a unique set of antibodies produced by B cells, that are released into the mucosal layer via transcytosis.
They block pathogen receptors or virulence factors and agglutinate pathogens of virulence factors to trap them (immune exclusion)
what are two ways to induce IgA production?
- T cell-dependent IgA induction
- T cell-independent IgA induction
4 main functions of IgA:
- secreted IgA on the gut surface can bind and neutralize pathogens and toxins
- able to bind and neutralize antigens internalized in endosomes
- IgA can export toxins and pathogens from the lamina propria while being secreted
- binding of IgA to Dectin-1 on M cell allows transport of antigen to DC-SIGN+ dendritic cell
what is the importance of the regulatory T cell?
it is the heart of a complex system
traits of the regulatory T cell
- subset of CD4+ T cells
- Two origins: Thymus vs Periphery
- Master transcription factor: Foxp3
- general functions:
1. peripheral tolerance
2. tissue repair mechanisms
3. establishment of long-term memory response