9: Mucosal immunity 🏁 Flashcards
3 major classes of mucosal tissue
respiratory/gastrointestinal/urogenital
Most deaths due to mucosal infection (class of infection + countries)
Acute respiratory infection lead to 4 million death, overall USA has most mucosal infection death (500k) followed by Brazil
What is the Waldeyer’s ring?
mucosal tissues around gut and airway bear lymphoid tissues (MALT) of tonsils and adenoids that form a ring
What are the first line defense mechanism of of immune system in the gut?
Mechanical
- epithelial cells joined by tight junctions
- longitudinal flow of air / fluid
Chemical
l- ow pH
- enzymes (peroxidase for radicals, lysouyme for murein, lactoferrin for Fe competition)
- antimicrobial peptides (alpha, beta-defensins, Cathelicidin, Histatin, S100 proteins) for membrane penetration and influence of bact. functions
Microbiological
- normal flora (commensals)
What are S100 proteins? Name example + function
Antimicrobial peptides like S100A7 (Psoriasin) that is produced by epithelial cells to protect against E.coli
Which 2 forms of IgA exists? Name function and characteristics o secretory IgAs
- Monomeric and Dimeric form
- Secretory IgA (dimeric) has 2 basic chains: J chain + secretory component
- secretory component helps to transport dimer to mucosal cell surface + protects IgA from proteolytic digestion
- monomeric form binds to CD89 on macrophages, neutrophils and eosinophils
Functions
- monomer: formes immune complexes and binds to CD89, activates APCs, induced cellular immune reaction
- dimer: neutralisation of antigens on mucosal surface, prevents attachement and movement of microbes, antigen transport across epithelium via poly-Ig receptor
How is IgA produced?
produced by plasma cells in lamina propria, derivee from B-2 cells in Peyer’s pacthes and B-1 cells in lamina prpria
Which cel transport antigen from mucosal barriers to lymph nodes?
DCs that migrate to epithelial layer and even extens into lumen to capture antigen, then migrate to myph nodes for antigen presentation
M cells: location, function
location: epithelial Peyer’s patches containing M cells with membrane ruffles
function: uptake of antigens by endo and phagocytosis, transportion of antigen across M cell in vesicles and release at basal surface, antigen can be bound by DCs to activate T cells
Which immune cells are located within epithelium ?
intraepithelial CD8+ lymphcytes that lie within epithelial lining
What is oral tolerance?
oral antigen administration can induce tolerance
- immune system can learn to tolerate non-self antigens that are encountered in the gut
- When antigens are ingested orally, they are exposed to specialized immune cells in the gut-associated lymphoid tissue, such as dendritic cells and T cells.
- These cells can induce a state of immune tolerance by promoting the development of regulatory T cells, which suppress the activation of other immune cells that would normally attack the antigen.
- Low tolerance + non-harmfull antgens like food proteins or commensals leads to stronger tolerance induction with only some local IgA production, no Absin serum, no t cell response and no memory
Give an example where commensals can induce disease?
Morbus Chrohn: a barrier disfucntion of intestinal mucosa leads to inflammation induced due to immune stimulation by commensals
Salmonella leads to mucosal infections. Name 3 ways.
How can Salmonella bacteria be killed?
- enter and kill M cells, then infect macrophages and epithelial cells
- invade luminal surface of epithelial cells
- enter endrites of DCs that are extended to lumen
Killing by release of defensins by paneth cells that are specialized epithelial cells, granules contain prodefensin 5 and trypsin to activates prodefensin 5 due to cleavage
What is difference between immature and mature DCs and how is differentiation induced?
Immature DC induce tolerance of antigens, in presense of commensals, production of TGF.ß, … inhibits DC maturation, DCs weak signal leads to T cell differentiation into regulatory T cells
Mature DC induce T cell response, invasive microorganisms penetrate epithelium to mature DCs, activated DCs lead to differentiation into effector TH1 or TH2 cells
Is there another function that commensals offer?
some block TLR signalling by activating PPAR-y that removes NF-kappaB from nucleus or by blocking degradation of phosphorylated I-kappaB that prevents NF-kappaB translocation
