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22 Cards in this Set

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DAMPs vs PAMPs

DAMPs: danger associated molecular patterns that are endogenous molecules that create an immune response by being somewhere they are not supposed to be (DNA in cytoplasm)




PAMPs: pathogen associated molecular patterns that are distinct markers on foreign invaders

What recognize and bind DAMPs and/or PAMPs?

Pattern Recognition Receptors

What is the result of ligand binding to a PRR?

It induces signalling pathways that can modulate the expression of important genes (cytokine genes)

DAMP Binding

DAMPs are often intracellular proteins that are released from the cell entering the extracellular space and enabling them to bind to PRR initiating a signalling pathway

What sort of gene expression is induced by DAMP binding?

Inflammatory cytokine genes (IL-6, Il-1, and TNF-a)

Where were toll like receptors initially discovered and how?

They were initially discovered in fruit flies, insects without these receptors quickly succumbed to fungal infections

What amino acid is important for ligand binding in TLRs?

A series of leucine repeats allows for ligand binding in the TLRs



What is the PAMP recognized by TLR4?

LPS or lipopolysaccharide a component of bacterial cell membranes

What four proteins are required for the binding of LPS and signal transduction?

A homodimer of TLR4, LPS binding protein, and CD14

What is the result of LPS binding with the TLR4 complex?

Binding activates a protein called MyD88, which activates the transcription factor NF-kB which will in turn lead to transcription of cytokine genes

In addition to cytokine gene expression what other genes are expressed upon TLR4 activation?

Activation will also cause the expression of cell surface protein responsible for antigen presentation

Where is TLR7 found?

TLR7 is found in endosomes that form is cell during the entrance of viruses

What PAMP does TLR7 primarily recognize?

TLR7 primarily recognizes ssRNA in endosomes as ssRNA is considered foreign in these structures (should only be found in nucleus or cytoplasm)

What is the result of ssRNA binding to TLR7?

Binding results in the activation of a signalling pathway that results in IFN (type 1) gene expression

What is the role of IFN?

It is an anti-viral protein that blocks viral replication and further infection



How do viruses propagate with interferon?

Viruses produce proteins that interfere with interferon signalling pathways

NOD-Like receptor ligand

Are similar to TLRs, but they bind peptidoglycan fragments

Why bind peptidoglycan fragments?

Peptidoglycan fragment in the intracellular space are indication of pathogen phagocytosis and therefore this may likely be carried out by macrophages

Transcription factor activated by NOD-like receptors?

NF-kB

What is RIG-1?

Retinoic Acid inducible gene 1

Where might one find RIG-1 like helicases and what do they bind and how do they recognize it?

These enzymes are found in the cytoplasm where they bind viral RNA because it doesn't have a poly a tail or guanosine cap

What is the result of RIG-1 helicase binding?

Activation of interferon gene expression similar to with NOD-like receptors