Manipulating the Immune Response

Question 1

TLR1/TLR2

Answer 1

Peptidoglycan, lipoarabinomannan, zymosan, lipoproteins.

Question 2

TLR6/TLR2

Answer 2

Peptidoglycan, lipoarabinomannan, zymosan, lipoproteins.

Question 3

TLR4

Answer 3

Lipopolysaccharide, heat shock protein 60, heat shock protein 70 (HSP60, HSP70)

Question 4

TLR5

Answer 4

Flagellin

Question 5

Mannose-binding receptor location

Answer 5

Membrane-bound

Question 6

TLR3

Answer 6

ssRNA

Question 7

TLR7

Answer 7

ssDNA

Question 8

TLR9

Answer 8

CpGDNA

Question 9

TLR3 location

Answer 9

Endosomally membrane-bound

Question 10

TLR7 location

Answer 10

Endosome membrane

Question 11

TLR9 location

Answer 11

Endosome membrane

Question 12

RIG-like helicase ligand

Answer 12

Viral DNA

Question 13

Nod-like receptor ligand

Answer 13

Degraded gram negative peotidoglycan, DAMPS

Question 14

Macrophage response to PRR-PAMP binding

CASSIE CLyP

Answer 14

Chemokines
Antiviral cytokines
Stimulatory cytokines
Suppressive cytokines
Inflammatory cytokines
Eicosanoids
Complement proteins
Lysozyme
y
Prostaglandin

Question 15

Macrophage-released chemokines

Answer 15

IL-8

Question 16

Macrophage-released anti-viral cytokines

Answer 16

Interferon alpha

Question 17

Macrophage-released stimulatory cytokines

Answer 17

IL12, GM-CSF

Question 18

IL12 role

Answer 18

T-cell, NK cell activation

Question 19

Macrophage-released suppressive cytokines

Answer 19

IL10, TGF-beta

Question 20

Macrophage-released inflammatory cytokines

Answer 20

IL1, IL6, TNF-alpha

Question 21

IL1 role

Answer 21

Increase permeability of vascular endothelium

Question 22

IL6 role

Answer 22

Increase acute-phase proteins

Question 23

Possible adjuvants
1)
2)

Answer 23

1) TLR7 agonists to induce stronger antiviral response.

2) TLR9 agonist to induce appropriate T-cell and cytokine response.

Question 24

Endotoxic shock pathogenesis

Answer 24

Overstimulation of TLR4 from LPS in blood.

Oversecretion of IL1, TNF-alpha by macrophages.

Question 25

Endotoxic shock treatment

Answer 25

TLR4 antagonists.

Question 26

Gout, diabetes II treatments

Answer 26

Antibodies directed against IL1, IL1R (antiinflammatory)

Question 27

Rheumatoid arthritis treatment

Answer 27

TNF-alpha antagonists

Question 28

Therapeutic use for TLR2 agonists

Answer 28

Treat allergic rhinitis. | Reduce IL2 release, less IgE, eosinophil recruitment.

Question 29

Passive immunity can be naturally and artificially given

Answer 29

Breast milk. | Injection.

Question 30

``` Types of vaccine: 1) 2) 3) 4) ```

Answer 30

1) Virus-like particles 2) Live attenuated 3) Killed pathogen 4) Subunit of antigen VLKS

Question 31

Pros of live attenuated

Answer 31

1) Can be delivered orally, intravenously, parenterally 2) Long-lived immunity 3) Replicate in appropriate tissue 4) Spectrum of antigens

Question 32

Cons of live attenuated

Answer 32

Reversion to virulence | Cold chain

Question 33

Killed/extracted antigens pros

Answer 33

No cold chain | No reversion to virulence

Question 34

Killed/extracted antigens cons

Answer 34

Delivered parenterally Shorter-lived immunity (need boosters) Doesn't replicate --> higher doses needed Restricted number of antigens

Question 35

B-Cell induction without Th cells

Answer 35

Low-affinity IgM produced

Question 36

Effective B-cell induction requires:

Answer 36

Th cell activation

Question 37

How CD4+ cell induces B cell isoconversion

Answer 37

T-cell CD40L binds B-cell CD40 | Cytokines released by Th provide signal 3

Question 38

Effective CD4+ induction: 1) 2) 3)

Answer 38

1) Signal 1) Antigen endocytosed by APC, presented on MHC II 2) Signal 2) PAMP-PRR binding induces APC to express CD80, CD86. CD80, CD86 bind T-cell CD28 3) Signal 3 can be provided to skew Th response.

Question 39

Way to induce APC CD80, CD86 expression

Answer 39

Adjuvants added to vaccine

Question 40

Effective CD8+ induction:

Answer 40

1) Signal 1) Antigen must be presented on MHC I | This requires exit from endosome.

Question 41

Ways to induce antigen to be presented on MHC I

Answer 41

1) Live attenuated will automatically exit endosome. 2) Coat antigen in avirulent viral vector. 3) Lipid Immune Stimulatory COMplexes (ISCOM)