3- Innate Immunity: Induced Response

What are the steps for initiating signaling?

1. receptor binds ligand

2. perpetuation of signal

3. transcription factor

4. gene expression

What does the innate induced response entail?

signaling

Where are receptors found?

generally expressed on cell surface

How is the signaling pathway activated?

ligands bind to receptors

What happens after ligands bind to receptors?

signaling molecules carry signal downstream until reach transcription factor

What induces gene expression?

transcription factor

What can gene expression cause?

effector functions determined by cell type, activated receptor, etc

ex → AMP production, increased phagocytosis, cytokine production, induce proliferation, activate other cells

How does perpetuation of the signal occur?

kinases, phosphatases, ubiquitin ligases

Which ubiquitin ligase is used in signaling?

K63ub

Which ubiquitin ligase is used to degrade proteins?

K48ub

Self

healthy human cells, want them to be there, won’t initiate a response

What happens if there is a response to self?

failure of self, autoimmune/self attacking

What can a receptor distinguish?

self vs microbe, w/in self = non-self, altered, true self

Non-Self

microbial cells, receptors can distinguish between our cells & microbial cells, immune system activated

Altered Self

infected or cancerous cells, normal proteins in us modified to tell immune system we’re infected or cancerous, immune response activated but NO MICROBE

Tissues Resident Macrophages

all tissues have macrophages

• long lived

• able to self renew → can make new macrophages

• scavengers → breakdown dead/dying cells, microbes in tissues, recycling janitors

• phagocytosis

Why are immune cells unique in comparison to other terminally differentiated cells?

terminally differentiated cells → lose capacity to make new cells, not long lived

immune cells are

Macrophage receptors

scavenger receptor or others (CD14, C3/C4, TLRs)

Scavenger Receptors

macrophage receptor

• no infxn → recognize dead/dying cells

• infxn → recognize components on microbes

What microbial components can scavenger receptors detect?

LPS, CPG DNA (methylated DNA diff from ours), sugars

SR-E3

scavenger receptor, mannose receptor, CD206

• does phagocytosis, no signaling

• targets bacteria

• LIGANDS → LPS, CPs, ManLam

What other receptors are macrophage receptors?

• CD14 → lipopolysaccharide receptor

• complement receptors C3 & C4 → phagocytose things w/ C3b tags

• toll-like receptors (TLRs)