Innate Defenses Flashcards
Innate defenses are an arsenal of
pre-existing or rapidly synthesized effector and signalling proteins
Innate defense combine physical barriers with molecular effectors
epithelial cells and mucous barriers
patrolling immune cells (macrophages, NK cells, dendritic cells)
soluble mediators- complement and defensins
cytokines- IFN A/B, TNF-A, IL-1, IL-6, IL-12
overall process of viral recognition and innate activation
- viral recognition via receptor 2. signalling to nucleus via adaptors and kinases 3. activation of transcription factors 4. amplified production of antiviral effector proteins (often the first to be transcribed is IFN-A/IFN-B)
PRR’s = receptors
these are on the innate cells to detect the foreign viral products
name PRR
TLR RIG-1-like-receptors CDR NOD-like-receptors C-type lectin-receptors
TLR = (location)
endosomes and plasma membrane
RIG-1- like receptors (location)
cytoplasm (mitochondria anchored)
CDR (location)
cytoplasm
NOD (location)
cytoplasm
C-type lectin (location)
plasma membrane
PAMPs
pathogen-associated molecular patterns
Examples of PAMPs
cytoplasmic DNA dsRNA naked nuclear DNA viral genome intermediates glycoproteins or capsid proteins
Toll-like receptors involved in viral detection
TLR3-dsRNA
TLF7/8-ssRNA
TLR9- cpG methylated DNA
TLR13- rRNA
when TLR’s sense virus, it creates a signaling cascade that invovles______ and leads to______
adaptors and kinases; and leads to transcription of pro-inflammatory cytokines (TNF-A, IL-1, IL-6, IL-12) and type 1 interferons (A and B)
viral dsRNA activation pathway
- dsRNA binds to TLR3 and comes into cell
- binds to OAS which undergoes conformational change and creates 2’-5’linked oligoadenylates
- 2’-5’-linked oligoadenylates act as second messages and activate RNaseL
- RNase L dimerizes and degrades cellular and viral RNA
viral ds (cytoplasmic) DNA pathway
- dsDNA binds to CDN
- binds to cGAS in cytoplasm
- cGAS is activated to form cGAMP (2’-5’)
- cGAMP 2’-5’ binds to and activates STING on ER
- STING translocates to perinuclear Golgi where it gaines signaling activity and signals for production of pro inflammatory and antiviral proteins
- cGAMP 2’-5’ can also go to neighboring cells via cell junctions, bind to a STING, and initiate antiviral activity in those cells
Interferons are what?
secreted immune peptides
Type 1 Interferons
IFN alpha and beta
Source: fibroblasts, epithelial cells, macrophages, monocytes, and plasmacytoid dendritic cells
Stimulus: virus, microbial products
**cells that will be in the periphery encountering a lot of pathogens
Type 2 Interferons
IFN gamma
Source: T cells and NK cells
Stimulus: immune activation
Type 3 Interferons
IFN lambda
Source: plasmacytoid dendritic cells and epithelial cells
Stimulus: viruses or microbial products
General way that interferon signaling works
IFN binds to an IFN receptor
receptor will activate kinases (tyk2 and jak1)
kinases will phosphorylate transcription factors STAT1/2 sitting in the cytoplasm
these will go to the nucleus (and may associate with other factors like IRF9) and induce the transcription of ISGs which tend to be for pro-inflammatory and antiviral proteins
ISGs have ______actions and viruses are controlled by ________ with regard to ISGs
diverse actions
some ISGs may have some specificity
control of the virus is likely by a combination of many ISGs
IFN as therapy for…
AIDS-related Kaposis sarcoma herpes virus
Hep B
Hep C
non-viral disorders- autoimmune disorders, cancers, osteoporosis
IFN bad because
flu-like symptoms, neutropenia, and hepatotoxicity
