Mucosal immunity

Epithelial barriers

Skin Mucosa

Skin3 m2 Mucosa

300 m2

↑ Ag pressure(food,bacteria of GIT..)80% imunoactive cells90% infections 5-9 g IgA /day

Mucosal immunity

Tasks

Infectious diseases defense

Tolerance of innocent Ag

Moicroflora –host symbiosis

• Colonization rezistance• Epithelial cells activation• Immune system development

• ? Why comensal bacteria don´t induce inflammation under physiologic conditions

Ag uptake

• DC• M cells.• Enterocytes• Macrophages

Ag presentation

Proffessional APC : DC, B cells, Macrophages

Innocent Ag– presented by immature DC (↓CD80,86), IL-10, TGF-β, Th2, Th3 Oral tolerance

Pathogen – presented by mature DC (↑ CD80,86), IL-12Inflammation

Recirculace

Homing

• α4β7 integrin (homing receptor) – MadCAM – 1(adresin)

Common mucosal immune systemSpolečný slizniční imunitní systém

IgA transport

IgA properties and function

• Proteases resistance• Neutralization of viruses and toxins (also IC)• Microbs Adherence and invasion inhibition• Opsonization• ADCC• Antiinflammatory effect

Oral tolerance

High doses of Ag - Anergy,deletion of autoreactive lymphocytes

Low doses of Ag - Active supression, inhibitory cytokines production (TGF-β)

Experimental models• RA• SM• DM

Mucosal vaccines

• Replicating Ag• Corpuscular Ag aimed to M cells – vectors

(liposomes, micropatticles)• Epithelial cell binding proteins (cholera toxin)