Innate immunity 2

Question 1

Neutrophil function

Answer 1

Phagocytosis

Reactive oxygen and nitrogen species

Antimicrobial peptides

NETs: neutrophil extracellular traps

Question 2

Macrophage function

Answer 2

Phagocytosis

Inflammatory mediators

Antigen presentation

Reactive oxygen and nitrogen species

Cytokines

Complement proteins

Question 3

Dendritic cell function

Answer 3

Antigen presentation

Costimulatory signals

Reactive oxygen species

Interferon

Cytokines

Question 4

Natural killer cell function

Answer 4

Lysis of viral infected cells

Interferon

Macrophage activation

Question 5

Phagocyte recruitment

Answer 5

Cytokines dilate local blood vessels

Chemokines attract monocytes and neutrophils to the infection

Cell adhesion molecules are upregulated on the endothelium which bind to integrins on the leukocyte

Question 6

Phagocytosis performed by

Answer 6

Neutrophils and macrophages

Question 7

Opsonins

Answer 7

Complement components (C3b)

Collectins (mannose binding lectin)

Antibodies

Question 8

Phagocytic receptors

Answer 8

Complement receptors

Fc receptors

Manose receptor

Scavenger receptor

Question 9

Neutrophil extracellular traps

Answer 9

When activated some undergo a special form of cell death termed NETosis

During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding phagocytosis

Question 10

Pattern recognition receptors

Answer 10

Receptors able to recognise conserved structures

Recognise patterns termed: pathogen associated molecular patterns (PAMPs)

Question 11

Types of PRRs

Answer 11

Toll like receptors (TLRs)

NOD like receptors (NLRs)

Rig-I like receptors (RLRs)

Cytosolic DNA sensors (CDS)

Question 12

PAMPs

Answer 12

Microbes evolve rapidly, so innate immunity must focus on highly conserved and essential components of microbes

Question 13

DAMPs

Answer 13

Damage associated molecular patterns, molecules released from necrotic cells

Question 14

Drosophila toll receptor

Answer 14

Mutagenesis work on drosophila revealed two members of the toll family, dToll and 18-wheeler

Important for development

Important for immunity to the fungal and bacterial infections

Mammalian equivalent are the toll like receptors

Question 15

Toll like receptor structure

Answer 15

Extracellular
- LRR domain- site of pathogen binding

Cytosolic side
- TIR domain- conserved stretch of 200 amino acids

Question 16

TLR signalling induces genes that function in host defence

Answer 16

Pro-inflammatory cytokines

Chemokines

MHC and co-stimulatory molecules

Antimicrobial peptides and complement components

Question 17

Nod like receptors

Answer 17

Cytoplasmic pattern recognition molecules

Two major groups- NLRCs and NLRPs

Question 18

NLRCs

Answer 18

NLRC1
NLRC2

They have a leucine rich domain which can bind to peptidoglycan which is present on the cell membrane of most bacteria

Question 19

NOD1 and NOD2

Answer 19

Detect similar yet distinct peptides of peptidoglycan

NOD1 binds y-glutamyl diaminopimelic acid

NOD2 binds muramyl dipeptide

Question 20

NOD2 gain of function

Answer 20

Mutation linked to early onset sacroidosis where granulomas develop in the organs of the body

Question 21

NOD2 loss of function

Answer 21

Mutation is associated with susceptibility to Crohn’s disease, a chronic intestinal inflammatory disorder

Question 22

NLRPs

Answer 22

The best characterised is NLRP3

NLRP3 is activated by cellular stress; K+ efflux, ATP, reactive oxygen species and lysosomal damage

Inflammasome is essential for IL-1 and IL-18

Question 23

Inflammasome

Answer 23

Activated by cellular infection or cell stress

• uric acid crystals
• asbestos
• silica
• amyloid beta
• islet amyloid polypeptide
• hemozoin

Question 24

RIG-I-like receptors

Answer 24

RIG-I and MDA5 are sensors of cytoplasmic RNA, a replication intermediate for viruses

They signal to induce pro-inflammatory cytokines and IFN

Question 25

RIG-I

Answer 25

Binds to single stranded RNA containing 5’-triphosphate

Recognition of

• flaviviruses
• orthomyxoviruses

Question 26

MDA5

Answer 26

Preferentially recognises long double stranded RNA

Critical for picornavirus detection

Mutations (rare) are beginning to be associated with IFN related diseases

Question 27

Cytosolic DNA sensors

Answer 27

Stimulator of interferon genes (STING)- associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain of function mutation in TMEM 173, the gene that codes for sting

Patients have abnormal inflammation throughout the body, especially in the skin, blood vessels and lungs

Question 28

Acute phase response

Answer 28

Induced by cytokines such as TNF, IL6 and IL1 during infection and inflammation

Acute phase proteins are mainly produced by the liver

Induces opsonisation/ phagocytosis

Can activate the complement pathway

Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation