Manipulating the Immune Response Flashcards
TLR1/TLR2
Peptidoglycan, lipoarabinomannan, zymosan, lipoproteins.
TLR6/TLR2
Peptidoglycan, lipoarabinomannan, zymosan, lipoproteins.
TLR4
Lipopolysaccharide, heat shock protein 60, heat shock protein 70 (HSP60, HSP70)
TLR5
Flagellin
Mannose-binding receptor location
Membrane-bound
TLR3
ssRNA
TLR7
ssDNA
TLR9
CpGDNA
TLR3 location
Endosomally membrane-bound
TLR7 location
Endosome membrane
TLR9 location
Endosome membrane
RIG-like helicase ligand
Viral DNA
Nod-like receptor ligand
Degraded gram negative peotidoglycan, DAMPS
Macrophage response to PRR-PAMP binding
CASSIE CLyP
Chemokines Antiviral cytokines Stimulatory cytokines Suppressive cytokines Inflammatory cytokines Eicosanoids Complement proteins Lysozyme y Prostaglandin
Macrophage-released chemokines
IL-8
Macrophage-released anti-viral cytokines
Interferon alpha
Macrophage-released stimulatory cytokines
IL12, GM-CSF
IL12 role
T-cell, NK cell activation
Macrophage-released suppressive cytokines
IL10, TGF-beta
Macrophage-released inflammatory cytokines
IL1, IL6, TNF-alpha
IL1 role
Increase permeability of vascular endothelium
IL6 role
Increase acute-phase proteins
Possible adjuvants
1)
2)
1) TLR7 agonists to induce stronger antiviral response.
2) TLR9 agonist to induce appropriate T-cell and cytokine response.
Endotoxic shock pathogenesis
Overstimulation of TLR4 from LPS in blood.
Oversecretion of IL1, TNF-alpha by macrophages.
Endotoxic shock treatment
TLR4 antagonists.
Gout, diabetes II treatments
Antibodies directed against IL1, IL1R (antiinflammatory)
Rheumatoid arthritis treatment
TNF-alpha antagonists
Therapeutic use for TLR2 agonists
Treat allergic rhinitis.
Reduce IL2 release, less IgE, eosinophil recruitment.
Passive immunity can be naturally and artificially given
Breast milk.
Injection.
Types of vaccine: 1) 2) 3) 4)
1) Virus-like particles
2) Live attenuated
3) Killed pathogen
4) Subunit of antigen
VLKS
Pros of live attenuated
1) Can be delivered orally, intravenously, parenterally
2) Long-lived immunity
3) Replicate in appropriate tissue
4) Spectrum of antigens
Cons of live attenuated
Reversion to virulence
Cold chain
Killed/extracted antigens pros
No cold chain
No reversion to virulence
Killed/extracted antigens cons
Delivered parenterally
Shorter-lived immunity (need boosters)
Doesn’t replicate –> higher doses needed
Restricted number of antigens
B-Cell induction without Th cells
Low-affinity IgM produced
Effective B-cell induction requires:
Th cell activation
How CD4+ cell induces B cell isoconversion
T-cell CD40L binds B-cell CD40
Cytokines released by Th provide signal 3
Effective CD4+ induction:
1)
2)
3)
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.
Way to induce APC CD80, CD86 expression
Adjuvants added to vaccine
Effective CD8+ induction:
1) Signal 1) Antigen must be presented on MHC I
This requires exit from endosome.
Ways to induce antigen to be presented on MHC I
1) Live attenuated will automatically exit endosome.
2) Coat antigen in avirulent viral vector.
3) Lipid Immune Stimulatory COMplexes (ISCOM)