Immune Therapies Flashcards
why manipulate the immune response
• Promote protective immune responses
○ Vaccination
○ Fight tumours
○ Treat immunocompromised patients
• Suppress unwanted immune responses
○ Chronic inflammation
○ Autoimmunity
○ Allergy
why vaccinate?
- Most effective strategy to prevent infectious disease
- Promote human health
- Primary aim to induce immunity in individuals
- Successful programmes protect entire communities and populations
what is included in the UK vaccination programme
- Pertussis (whooping cough)
- Diphtheria
- Tetanus
- Polio
- Hib
- Hepatitis B
- MenB and MenC
- Rotavirus
- Pneumococcal conjugate vaccine (PCV)
- Measles, mumps, rubella (MMR)
- Seasonal flu
- Human papilloma virus (HPV)
○ Now offered to both boys and girls
what is included in the 6 in 1 vaccine
- Pertussis (whooping cough)
- Diphtheria
- Tetanus
- Polio
- Hib
- Hepatitis B
name the stages in the evolution of immunisation programme
- stage 1 = pre-vaccine
eg corona virus - stage 2 = increasing coverage
- stage 3 = loss of confidence
eg MMR - stage 4 = resumption of confidence
- stage 5 = eradication
Eg smallpox
name a case when there was loss of the public trust in vaccines
paper published showing incorrect relationship between MMR vaccine and autism
caused an increase in the incidences of measles, mumps and rubella
how do vaccines work
replication immunity from natural infection without the illness / disease
exposing our immune system to disease causing microbial antigens without causing disease
what is the primary aim of vaccination
stimulate adaptive immunity
generate long term immunological memory
what is the most important goal of vaccination
production of high affinity IgG
what is the primary response to natural infection
○ Low specificity IgM produced first
○ High specificity IgG takes longer
Requires T cell help
what is the secondary response to natural infection
○ More rapid
○ More effective
§ Highly specificity IgG produced by long-lived plasma cells
what are virulence factors
disease causing factors expressed by microbes
how does the microbial challenge affect the host response
antigens and virulence factors act on the host
how does the host response affect the microbial challenge
innate and adaptive immune response attacks
what are the different types of vaccines
• Live attenuated • Inactivated • Subunit (purified antigens) ○ Recombinant ○ Toxoid ○ Polysaccharide ○ Conjugate
what are live attenuated vaccines
• Live pathogen but weakened via genetic manipulations
• Capable of replication within host cells
○ The pathogen can replicate in your tissues
- Excellent life long immunity
- Potentially pathogenic in immune-compromised
- Examples:
- MMR
- BCG
- Rotavirus
how do live attenuated vaccines work
- attachment
influenza virus becomes attached to target epithelial cell - penetration
the cell engulfs the virus by endocytosis - uncoating
viral contents are released - biosynthesis
viral RNA enters the nucleus, where it is replicated by the viral RNA polymerase - assembly
new phage particles are assembled - release
new viral particles are made and released into the ECF
the cell which is not killed in the process continues to make new virus
[actually have no clue what any of this means it is in a diagram but dunno if it is actually associated with how this vaccine works lol]
what are inactivated vaccines
• Killed through chemical or physical processes
○ Take the live organism and kill it but it will remain structurally intact
• Cannot replicate or cause disease
○ Safer vaccine
• Weak immunity
• Several doses required
○ Needs booster doses to generate the protective immunity
• Examples:
○ Polio
○ Pertussis
what are subunit ((purified antigens)) vaccines
- No live components
- Takes 2/3 doses to get the long lived memory response you want
• Recombinant - produced by genetic engineering
○ Hep B
○ HPV
• Toxoid - inactivated bacterial toxins
○ Diphtheria
○ Tetanus
• Polysaccharide - encapsulated bacteria - T cell independent
• Conjugate - polysaccharide antigens linked to proteins
○ PCV
○ Hib
○MenC
what are adjuvants
Enhance immune responses to vaccine antigens
Inactivated / subunit vaccines
what do aluminium / calcium salts do
Maintain and prolong antigen stability
Enhance and prolong antigen presentation
Granuloma formation
why is granuloma formation useful in vaccines
§ Makes sure the antigen stays at the intended site to be presented to your immune system for longer
If you didn’t have this granuloma then it might be washed away
what are the different routes of administration
• Intramuscular
hepatitis B
• Subcutaneous
eg measles
• Intradermal
eg BCG
• Intranasal
• Oral
eg rotavirus
is there rationale for a dental caries vaccine?
Bacterial aetiology
Cariogenic bacteria produce acids the demineralise tooth surfaces
what do mutans streptococci do
Extremely efficient at accumulating and producing carious surfaces
Extremely tolerant of low pH
Colonisation coincides with tooth eruption
Colonisation stimulates specific IgA and IgG
what are the biological considerations to dental caries vaccination
Mutans streptococci dominate environments frequently exposed to dietary carbohydrates
Mutans streptococci are not the only cariogenic bacteria in the oral biofilm
Other cariogenic species likely to fill niche
what are the ethical considerations to dental caries vaccination
○ Non-life threatening condition ○ Expensive ○ Other initiatives more cost effective ○ Child smile ○ Water fluoridation ○ Dietary advice
what has caused a reduction in infectious diseases
○ Widespread implementation of vaccination strategies
○ Cleaner drinking water
○ Better nutrition
○ Better living standards
what has successful vaccination programmes contributed to
Decreasing burden of infectious diseases
Increasing burden of NCDs associated with aging
name non-communicable diseases
○ Cardiovascular disease ○ Cancer ○ Metabolic disorders ○ Chronic kidney diseases ○ Autoimmune diseases ○ Neurodegenerative disorders
what is inflammation
the body’s defence to all types of challenges regardless of infectious, physical, environmental or psychological
name conventional immunosuppressive drugs
- Corticosteroids
- Non-steroidal anti-inflammatories (NSAIDS)
- Methotrexate (DMARDs)
- Biological therapies
what are corticosteroids
Synthetic versions of cortisol eg prednisolone
what do corticosteroids do
• Non specific anti-inflammatory function
• Treat wide range of inflammatory / allergic conditions
Systemic or topical application
what are the side effects of corticosteroids
Weight gain
Risk of infection
Risk of diabetes
Risk of hypertension
what are the physiological effects of corticosteroid therapy
- decreased inflammation caused by cytokines
- decrease NO
- decrease prostaglandins and leukotrienes
- reduced emigration of leukocytes from vessels
- induction of apoptosis in lymphocytes and eosinophils
what are NSAIDS
Non-Steroidal Anti-Inflammatory Drugs
= ibuprofen
= aspirin
what do NSAIDs do
• Reduce pain, inflammation and fever
• Constant use can lead to gastro-intestinal bleeding, liver and kidney problems
Interact with other medications (warfarin, diuretics, methotrexate)
what does DMARD stand for
Disease-modifying anti-rheumatic drug
eg methotrexate
what do DMARDs do
- Used at high doses at chemotherapy agent
- Used at low doses to treat inflammatory arthritis
- Multi-faceted anti-inflammatory effects
- Slow progression of arthritis
- Can be combined with biological therapies
what are biological therapies
• Genetically engineered antibodies made from human genes
• Directly target specific components of immune system to inhibit activity
○ B cell inhibitor (Rituximab)
○ Cytokine blockers (IL-1, IL-6, IL-17, TNFa)
• Moderate to severe RA patients to slow disease progression
• May be combined with DMARDs
what are anti-TNF therapies
• Five anti-TNF drugs licensed for RA in the UK
• All work in different ways
○ Infliximab binds soluble TNFa
○ Etanercept binds and blocks TNF receptor
• Patients can expect at least 20% clinical improvement
Often combined with methotrexate
how do TNF-therapies work in general
attacking immune cells release TNF which stimulates destruction of bone and cartilage and increases inflammation
a TNF blocker prevents TNF from binding to its receptor, limiting its destructive inflammatory effects
do anti-cytokine therapies have a role in the treatment of periodontitis
Elevated levels of cytokines in gingival tissues
Regulate immune-mediated bone destruction
what do targeted biological therapies do
harness the specificity of antibodies to target and block pathological inflammatory pathways
