L2.3 Immunostimulant

Question 1

Uses of immunostimulants

Answer 1

• Boosts immunity to infection/cancer
• Counter unwanted immunosuppression (mainly with anti-cancer drugs)
• Utilising immune system to interfere with pathological mechanism

Question 2

Immunostimulant therapies

Answer 2

• Vaccines & adjuvants
• Recombinant cytokines & growth factors
• Antibodies

Question 3

Forms of vaccines

Answer 3

• ‘killed’ viruses/bacteria
• ‘live’ attenuated virus/bacteria
  
  • Strain which is not as effective in human cells
  • Deletion of virulence genes
• Virus-like particles
• Proteins/peptides
• DNA
• Adjuvants

Question 4

How is a strong immunity generated

Answer 4

*Adjuvant needed (in addition to vaccine) to generate a strong immunity

• Virus infection → kill/damage cell → release necrotic factor (Danger signals - important for forming strong immunity) → triggers PRR (TLRs) → APC ↑co-stim molecules → Activates clonal T-cells & prolif

Question 5

What are adjuvants

Answer 5

• modifies effect of other organisms:
• Motifs that mimic organisms - CpG motifs
  
  • Stimulates TLR - 9 → Provides danger signals → ↑co-stim
  • Commonly found in bacteria genome
• Motifs that mimic organism - lipids
  
  • Also stimulates TLRs
• Metal oxides
  
  • Alum (aluminium potassium sulphate)
• Mast cell activator

Question 6

Alum

Answer 6

• Enhance antigen uptake by binding to dendritic cells → signalling cascade:
  
  • ↑internalisation of antigen
  • ↑MHC II & co-stim molecules
    
    • Stronger signal to T-cells

Question 7

Mast cell activators

Answer 7

• acts as vaccine adjuvant
• Compound 48/80 → polybasic activator of mast cells (via GCPR)
  
  • ↑Induction of AB
  • ↑IgA → Mucosal immunity
    
    • Stop virus penetrating body

Question 8

Mast-cell ‘particles’

Answer 8

• TNF stuck to mast cell particles following degranulation
  
  • Moves to lymph node → liberates TNF → enhanced adaptive immune responses

Question 9

Recombinant cytokines

Answer 9

• (Cytokine-augmented vaccines)
• Vaccines + cytokines → ↑T-cell proliferation & ↑recognition of aberrant cancer cells
  
  • Cancer cells are own cells ∴ hard to differentiate
  • Gardasil
• Recombinant:
  
  • Interferon α (recognise melanoma)
  • IL2 (recognise melanoma)

Question 10

Countering unwanted immunosuppressant effects

Answer 10

• Anti-cancer cells target bone marrow → ↓[neutrophils]
• G-CSF (granulocyte-colony stimulating factors) → ↑[neutrophils]
  
  • Counter drug-induced neutropenia

Question 11

Binding of AB to cancer cells causing cell death

Answer 11

1. AB dependent cellulary cytotoxicity (ADCC)
   
   • F-AB part bind to cancer cell, F-C bind effector mediating killing
2. Complement depednent cytotoxicity (CDC):
   
   • AB fix complement to triggering complement cascade
3. Cell activation leading to apoptosis
   
   • AB activate R (block/internalise) on cancer cell to apoptose

Question 12

Rituximab - for B-cell lymphoma

Answer 12

• B-cell lymphoma → ↑[CD20] on cancerous cell surface
• Rituximab recognises elevated levels of CD20
  
  • Target & focus immune system on lymphatic cells through complement cascades/utilising killer T-cells

Question 13

Prembrolizumab - for PD-1/PD-1L

Answer 13

• PD-1/PD-1L
• PD-1 found on T-cells (which dampens activity of T-cells)
• PD-1 activated by PD-1 Ligand found on tumour cells → T-cells recognise tumour cells but activity dampened
• Pembrolizumab (monoclonal antibody drug) → binds PD-1→ blocks negative signal from PD-1L
  
  • Allows T-cell destruction of tumour cells

Question 14

Vaccines for drug addictions

Answer 14

1. Conjugates drug to larger foreign protein (Normally too small to be recognise by IS)
2. Immune system generates AB that recognise free drug → neutralise

• Eradicate pleasurable/addictive effect → may free from addiction

Question 15

Vaccines for hypertension

Answer 15

• Vaccine targets ANG II by preventing binding to R→ ↓hypertension