What is receptory tlr?

Toll-Like Receptors (TLRs)

Toll-like receptors (TLRs) are a class of proteins that play a crucial role in the innate immune system. They are single-pass transmembrane receptors expressed on cells such as macrophages, dendritic cells, neutrophils, and epithelial cells.

Function:

TLRs function as pattern recognition receptors (PRRs), recognizing structurally conserved molecules derived from microbes, known as pathogen-associated molecular patterns (PAMPs). They also recognize damage-associated molecular patterns (DAMPs), which are released from damaged or dying host cells. This recognition triggers a cascade of intracellular signaling pathways, leading to the activation of immune responses, including:

• Production of cytokines and chemokines: These signaling molecules recruit and activate other immune cells to the site of infection or injury.
• Upregulation of co-stimulatory molecules: These molecules enhance the ability of antigen-presenting cells to activate T cells.
• Activation of transcription factors: Such as NF-κB and IRFs, which regulate the expression of genes involved in inflammation and immunity.
• Initiation of adaptive immunity: TLR activation bridges the innate and adaptive immune systems by promoting antigen presentation and T cell activation.

Structure and Localization:

TLRs have an extracellular leucine-rich repeat (LRR) domain responsible for PAMP recognition and an intracellular Toll/IL-1 receptor (TIR) domain essential for signal transduction. TLRs are localized either on the cell surface (e.g., TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10) or in endosomal compartments (e.g., TLR3, TLR7, TLR8, and TLR9). This differential localization allows TLRs to detect a wide range of PAMPs, including:

• Lipopolysaccharide (LPS)
• Lipopeptides
• Flagellin
• Double-stranded RNA (dsRNA)
• Single-stranded RNA (ssRNA)
• CpG DNA

Signaling Pathways:

Upon ligand binding, TLRs recruit adaptor proteins such as MyD88, TRIF, TRAM, and MAL/TIRAP. These adaptor proteins activate downstream signaling pathways, including:

• MyD88-dependent pathway: This pathway leads to the activation of NF-κB and MAP kinases, resulting in the production of pro-inflammatory cytokines.
• TRIF-dependent pathway: This pathway activates both NF-κB and IRF3, leading to the production of type I interferons (IFNs) and other inflammatory mediators.

Role in Disease:

TLRs play a critical role in host defense against infection, but they can also contribute to the pathogenesis of various diseases, including:

• Autoimmune diseases: Such as rheumatoid arthritis and systemic lupus erythematosus.
• Inflammatory diseases: Such as inflammatory bowel disease and atherosclerosis.
• Cancer: TLRs can promote or suppress tumor growth depending on the context.
• Sepsis: Excessive TLR activation can lead to a life-threatening systemic inflammatory response.

Therapeutic Potential:

TLRs are attractive targets for therapeutic intervention in a variety of diseases. TLR agonists can be used to enhance immune responses in vaccines and cancer immunotherapy, while TLR antagonists can be used to dampen inflammation in autoimmune and inflammatory diseases.

Here are some important subjects as links:

• Innate Immune System: https://www.wikiwhat.page/kavramlar/Innate%20Immune%20System
• Pathogen-Associated Molecular Patterns (PAMPs): https://www.wikiwhat.page/kavramlar/Pathogen-Associated%20Molecular%20Patterns%20(PAMPs)
• Cytokines: https://www.wikiwhat.page/kavramlar/Cytokines
• Chemokines: https://www.wikiwhat.page/kavramlar/Chemokines
• NF-κB: https://www.wikiwhat.page/kavramlar/NF-κB
• Interferons (IFNs): https://www.wikiwhat.page/kavramlar/Interferons%20(IFNs)