3. Innate Immunity 2

Question 1

Outline the stages of phagocytosis

Answer 1

(Performed by neutrophils and macrophages)

1. Phagocyte receptors (scavenger, MBL) recognise and binds to receptors on pathogen
2. Microbe internalised via endocytosis into phagosome
3. Phagosome containing pathogen fuses with lysosome to Phagolysosome
4. microorganisms are degraded

Question 2

Inflammasome

Answer 2

Complex formed by NLRP3

essential for IL-1 and IL-18 secretion

activation leads to cleavage of pro-IL-1 and pro-IL-18 to allow secretion

Question 3

Cryopyrin-Associated Periodic Syndromes (CAPS)

Answer 3

NLRP3 mutation

• gain of function mutation
• exon 3

XS production of IL-1
-Fever, joint pains

Includes

• Muckle wells syndrome
• Familial cold autoinflammatory syndrome

Treated with IL-1 receptor antagonist (IL-1RA, anakinra)

Question 4

Muckle wells syndrome

Answer 4

Type of CAPS
- Gain of function mutations in NLRP3

• Occurs spontaneously
• Triggered by cold, heat, fatigue, or other stresses.

Symptoms of fever, rash, arthralgia, conjunctivitis, uveitis, sensorineural deafness, and potentially life-threatening amyloidosis

Question 5

RIG-I-like receptors (RLRs)

Answer 5

• Senses cytoplasmic RNA
• signal to induce pro-inflammatory cytokines and IFN

E.g. RIG-1 and MDA5

Question 6

Stimulator of interferon genes (STING)

Answer 6

Protein encoded by TMEM173

activated by cGMP from viral DNA or GMP/AMP from bacteria

Question 7

SAVI

Answer 7

autoinflammatory disease

Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy

gain-of-function mutations inTMEM173

symptoms- inflammation of skin, BVs and lungs

Question 8

Acute Phase Response

• How is it detected?

Answer 8

Acute phase proteins are mainly produced by the liver

-induced by cytokines such as TNF, IL-6 and IL-1 during infection and inflammation

Effects

• Opsonisation
• phagocytosis
• activate complement pathway

detected by CRP and ESR proteins

Question 9

What are Neutrophil Extracellular Traps (NETs)

Answer 9

• Type of antimicrobial defense by neutrophils
• nuclear chromatin released from neutrophils undergoing cell death ‘NETosis’
• trapping microorganisms for phagocytosis

Question 10

PAMPs

Answer 10

Pathogen-associated molecular patterns

Question 11

DAMPs

Answer 11

Damage associated molecular patterns, molecules released from necrotic cells

Question 12

MyD88 deficiency?

Answer 12

life threatening infections

but improved with age

Question 13

TLR 3 Deficiency

Answer 13

recurrent HSV encephalitis

HSV-1 is a dsDNA virus, but during viral replication it produces dsRNA

Question 14

NOD2

• what does it bind?
• mutation?

Answer 14

binds muramyl dipeptide

gain of function mutation linked to early onset sarcoidosis

loss of function mutation is associated with susceptibility to Crohn’s disease

Question 15

What does NOD1 bind?

Answer 15

binds iE-DAP

Question 16

NLRP3/NALP3 activation

Answer 16

activated by cellular stress; K+ efflux, ATP, reactive oxygen species and lysosomal damage

Inflammasome is essential for IL-1 and IL-18 secretion

Question 17

Acute Phase Response

Answer 17

Induction of innate immune factors (cytokines such as TNF, IL-1, 6)

extra proteins being made in liver

clinically this results in raised ESR and CRP (a pentraxin)

Question 18

Waldenstrom macroglobulinemia

Answer 18

• Mutations in TLRs
• MyD88 gain of function mutation
• Non-hodgkin lymphoma
• B cell makes large amounts of IgM causing vision problems, bleeding, headaches

Question 19

Defects in TLRs is shown to be associated with what

Answer 19

Herpes simplex encephalitis (HSE): Inflammationofthebraindue toinfection with herpes simplex virus (HSV-1)

Question 20

NOD2 gain of function mutation is associated with what condition

Answer 20

early onset sarcoidosis

Question 21

NOD2 loss of function mutation is associated with what condition

Answer 21

Crohn’s disease

Question 22

MyD88 pathway

Answer 22

NF-kB

drives production of IL-1, IL-6, TNF-alpha (pro-inflammatory cytokines

Question 23

TRIF pathway

Answer 23

drives the production of pro-inflammatory cytokines

IFNa/B