Microbial Recognition and Responses in Innate Immunity

Question 1

what are the two aspects of innate immunity used to protect us against microbes

Answer 1

inflammation and the anti-viral state

Question 2

A sentinel cell that detects viruses and releases type I interferons

Answer 2

pDC - plasmacytoid dendritic cell

Question 3

A group of cytokines that initiate signaling that activates the antiviral state. They can be produced by most cells in the body, but pDCs are very efficient at producing these cytokines.

Answer 3

Type I interferons (type I IFNs)

Question 4

Molecules that are common in pathogens (such as viruses and bacteria) but not expressed in vertebrate cells.

• they are recognized by PRRs

Answer 4

Pathogen-associated molecular patterns (PAMPs)

Question 5

A common PAMP that is expressed on many gram-negative bacteria

Answer 5

Lipopolysaccharide (LPS)

Question 6

Receptors on immune cells that bind to PAMPs and activate an immune response. They are a key component of the innate immune system.

Answer 6

Pattern recognition receptors (PRRs)

ex: Main kind are TLRs (toll like receptors)

Question 7

A common PRR. Binds to and recognizes different PAMPs.

Answer 7

Toll-like receptors (TLRs)

Question 8

what are main PAMPS recognized on viruses by PRRs

Answer 8

for viruses main structures recognized are their nucleic acids: ssRNA, dsRNA, and dsDNA

Question 9

what are the PAMPs that are recognized on bacteria by PRRs

Answer 9

(gram negative and gram positive)
• gram negative- have lipopolysaccharide (LPS) on cell wall - lipid + carbohydrate chains, flagellin (makes bacteria swim)
• gram positive bacteria - peptidoglycan is cell wall component, flagellin, sugar chains called teichoic acids that come out of cell wall

Question 10

TLRs are expressed in two locations what are these and what is their purpose in both locations?

Answer 10

1. TLR expressed on the cell surface:
   ◦ Toll-like receptors (TLRs) expressed on the cell membrane recognize extracellular bacteria. When TLRs bind to bacteria, they initiate a signaling cascade that leads to the production of cytokines that initiate an inflammatory response.
2. TLR expressed in endosomes
   respond to nucleic acids and cause anti-viral state
   ◦ so viral molecules bind to PRRs expressed on endosomal membrane triggering pDCs IFNs and antiviral state

Question 11

describe the scenario for when bacteria invades and the inflammatory signaling response in the cell to produce cytokines

Answer 11

bacteria enters, TLR is on cell membrane and it recognizes PAMPs on bacteria (could be LPS if it is gram neg bacteria)

TLR dimerizes with ligand which sends signal for TF to migrate to nucleus to promoter gene for TNF & IL-1 cytokines to be transcribed

TLR signaling causes inhibitor bound to NF-kb to be degraded, then NF-kb floats into nucleus binds to target gene to induce transcription of the proinflammatory cytokines

Question 12

describe the scenario for when a virus invades and the antiviral state response in the pDC to produce IFNs

Answer 12

virus infects a cell which triggers release of IFNs by cell and pDCs

endosomal TLR recognize the PAMPs on virus (nucleic acids), this sends signal that induces a phosphorylation of a TF that goes into the nucleus binds to gene and transcribes IFNs

IFNs induce this antiviral state essentially protecting neighboring cells from infection

Question 13

what are the three specific pathways of complement activation?

Answer 13

specifc pathway: cleavage + generation of C3a & C3b

1. alternative- spontaneous cleavage of C3
2. classical- C3 cleaved when antibodies bind, C1q binds antibody on microbe
3. lectin- C3 cleaved when agglutinins bind to pathogen (clump pathogen)

all 3 pathways contribute to 3 functions - lysis, inflammation, & opsonization

• we have agglutinins and complement proteins in the blood which are part of innate immunity
  the complement pathway could be activated in 3 ways: spontaneously, by antibodies, and by agglutinins. this is how we get C3a and C3b

Question 14

a cascade of events that leads to inflammation and activates processes that can kill microbes in innate immunity
• can be activated in multiple ways
• always ends up with cleavage of protein C3 into C3a and C3b
C3a and C5a - can each activate inflammation
the first event that is activated by all pathways, regardless of the exact activation trigger, is the cleavage of the C3 protein

Answer 14

complement

Question 15

Antibodies are usually used in adaptive immunity. Which antibody is used in complement activation?

Answer 15

IgM

‣ IgM goes from planar to spider like which binds C1q - activates complement pathway, microbe shrivels and dies

Question 16

the virus that causes inflammation of the liver
170 million affected worldwide
may lead to cirrhosis (scarring of liver/lof)
chronic - may develop liver cancer

Answer 16

hepatitis C

Question 17

hepatitis C is an RNA virus. Triggers an innate immune response- antiviral state and IFN production. what is the original target for treatment and what is used now?

Answer 17

interferon was first targeted

now they use direct acting antivirals that target the viruses own replicative machinery
* have to use combination antivirals (virus ability to mutate fast)
now we have sustained cure of viral infection for Hep C