Dendritic Cells Flashcards
where are immature DCs found
periphery e.g. skin and mucosa
what qualities do immature DCs possess
efficient antigen capture but poor presentation
upon activation by danger signals, where do DCs go
secondary lymphoid tissues to present antigen to T cells
what qualities do mature T cells possess
inefficient at antigen capture but efficient at presentation
describe antigen capture by macropinocytosis
ruffles form on the surface of the dendritic cell. these extend and fuse with PM trapping cytosolic contents. these then form a macropinosome which moves into the cell, delivering the contents. This enables the non specific uptake of large amounts of antigens in the fluid phase
Describe the types of receptor involved in receptor mediated endocytosis by DCs
C type lectins such as the mannose receptor and DEC205 recognise glycosylated proteins. Fc receptors such as FcgRI bind to the Fc portion of antibodies. scavenger receptors such as Cd36 binds apoptotic bodies and receptors for HSPs bind Hsc70 and gp96 from tumour cells or infected cell.s
describe receptor-mediated endocytosis in DCs
ligand binding to the receptor leads to endocytosis in a clathrin coated pit and the formation of an endosome
what are DCs able to phagocytose
almost any bacterium, yeast cells, fungal hyphae and apoptotic and necrotic bodies
which direct innate signals are involved in dendritic cell maturation
toll like receptor binding to ligands. TLR2 binds Gram+ cell wall components TLR4 binds LPS in gram- basteria TLR5 binds flagellin TLR 9 binds DNA with unmethylated CpG dinucleotides
which indirect innate signals are involved in dendritic cell maturation
molecule secretion triggered by pathogens such as TNF-a. IL1b and PGE2
what is the immediate result of DC activation
increased macropinocytosis however levels return to normal after 1 hour
what are DCs in the skin known as
langerhans cells
upon activation of langerhans cells, what happens
adhesion molecule E cadherin is down regulated in keratinocytes to reduce interactions. Langerhans cells migrate through the dermis into the afferent lymphatic vessels to the lymph node where it hones into T cell concentrated areas. Homie is mediated by up regulation of CCR7 which binds CCL21 expressed by endothelial cells of lymphatic vessels and CCL-19 which is expressed by stromal cells in the T cell zone of lymph nodes
How is antigen presentation via MHC2 molecules regulated by maturation
in immature DCs the low activity of the vacuolar proton pump leads to high endosomal/lysosomal pH and high levels of cystatin C, a protease inhibitor, leads to low protease activity. MHC2 molecules are also rapidly endocytosed. In mature DCs the opposite results in high protease activity and limited endocytosis as well as a transient increase in MHC2 synthesis upon maturation
How is antigen presentation via MHC1 molecules regulated by maturation
in immature DCs there is just moderate expression of MHC1 molecules and MHC1 components such as TAP, tapasin and the immunoproteasome whereas in mature DCs these are expressed at high levels.
