What are Toll-like receptors ?• Are receptors involved in the innate immune system .• Recognize specific molecular patterns that are present in microbial components.
Stimulation of different TLRs induces distinct patterns of gene expression. Instructs the development of Activation of antigen-specific innate immunityacquired immunity.
Discovery of TLR ?• Named for their similarity to Toll, a receptor first identified in the fruit fly Drosophila melanogaster.• The first reported human Toll-like receptor was described by Nomura and colleagues in 1994.• 1997, Charles Janeway and Ruslan Medzhitov showed that a Toll-like receptor now known as TLR4 could, induce the activation of an adaptive immune response.
Where are TLR receptors found ?• TLR family members are expressed by: – Neutrophils. – Macrophages. – Dendritic cells. – Dermal endothelial cells. – Mucosal epithelial cells. – TLR2 and TLR4 expressed on B and T cells.
Are they intracellular or extracellular?• Most TLRs are on the cell surface except of TLR9, which is an intracellular• In MQ TLR4 expressed on cell surface and is internalized following engagement of the ligand.• In TLR4 epithelial cells it resides in the Golgi apparatus.
What are the functions of TLR receptors ? • Engagement of TLRs with their ligands leads to: – Pro-inflammatory cytokines, – Chemokines, – Effector molecules. • TLR2 Staphylococcus aureus . Haemophilus influenzae or with RSV persist longer in the lungs of TLR4-deficient mice .