Jan. 31st (Exam 1) Flashcards
What determines the specificity of TLRs for microbial ligands?
- The number of Leucine Rich Repeat Regions
- The actual amino acid sequence
What do the functional TLRs consist of?
2 TLR proteins that can either be homodimers or heterodimers.
Describe the layout of the TLR4 receptor.
It consists of two TLR 4 proteins that only associate with themselves.
What type of bacteria have LPS?
Gram negative bacteria.
Explain how the TLR4 Receptor and other proteins involved can detect the presence of LPS and initiate the production of cytokines.
- CD14 acts a co-receptor for TLR4 Receptor, by binding LPS that is released by gram negative bacteria, or otherwise.
- MD2 protein associates with the homodimer and form a complex with CD14 with LPS bound.
- Adaptor protein MyD88 binds to the TIR part of the TLR and, through a kinase cascade, releases NFKB from the protein it was bound.
- NFKB is a transcription factor that initiates the transcription of inflammatory cytokines.
What are NLRs?
Nod-Like Receptors (NLRs) are cytoplasmic signalling receptors that recognize the intracellular degradation products of pathogens.
What are NLRs similar in structure to?
Explain how NLRs can indirectly initiate the production of cytokines.
They look like TLRs but they are not membrane bound and instead are intracellular.
- They dimerize with the help of RIPK2 protein present in the cytoplasm and bind to degradation products of pathogens.
- Through a similar kinase cascade to TLR4 Receptor, NFKB is released from the protein that it is binded to.
- NFKB enters the nucleus and acts as a transcription factor for inflammatory cytokines.
What do activated macrophages secrete to recruit other cells?
They release Inflammatory Cytokines at the site of infection.
What do the cytokines IL-1beta and TNF-alpha do?
Induce the blood vessels to become more permeable.
This allows effect cells and the fluid that contains soluble effector molecules to enter the tissue.
What does the IL-6 cytokine do?
Induces the fat and muscle cells to metabolize, creating heat and raising the temperature in the infected tissue.
What does the CXCL8 cytokine do?
What is CXCL8 an example of?
They recruit neutrophils from the blood and guide them to the infected tissue.
Chemokine
What is a chemokine?
A chemokine is a chemoattractant cytokine.
What are the IL-1 family of cytokines responsible for?
What is the most studied one?
What are the subfamilies?
They are responsible for contributing to inflammation.
The most studied is IL-1beta
Subfamilies:
1. IL-1
2. IL-18
3. IL-36
What is the precursor to IL-1beta?
What activates it?
proIL-1beta
The precursor to IL-1beta is activated by active caspase 1 which has a precursor called procaspase 1.
What activates procaspase 1?
the inflammasome
What is the inflammasome?
This is the protein complex that involves NLRP3 procaspase 1 and increases the amount of IL-1beta in the cytoplasm.
Describe the positive feedback mechanism that we see with IL-1beta production.
Macrophages create IL-1beta that is secreted and bind to IL-1R on the surface of other macrophages or the same macrophages.
Through the activation of caspase 1 via cleavage induced by the inflammasome, we get more IL-1beta.
What do the inflammatory cytokines recruit to the site of infection?
Neutrophils.
What is the most abundant WBC?
Neutrophils
What does polymorphonuclear mean?
It means that the nucleus has variable shapes .
Are neutrophils long or short-lived?
They are short lived.
What type of cell is recruited first to the site of an infection?
What does their arrival signify?
Neutrophils
The inflammatory response.
What is CXCL8?
This is a chemokine that is made by activated macrophages, which acts to attract neutrophils
The movement of neutrophils from the blood vessels to the infected tissues is facilitated by what?
Adhesion molecules that are on both the endothelium and the leukocytes.
