Immune Therapies Flashcards
what is the main reason for immune therapies
therapeutic benefit
what 3 things promote protective immune responses
vaccination
fight tumours
treat immunocompromised patients
what conventional and targeted immune therapies are used to suppress unwanted immune responses
chronic inflammation
autoimmunity
allergy
4 reasons why we vaccinate
Most effective strategy to prevent infectious disease
- Second to clean drinking water
Promote human health
Primary aim to induce immunity in individuals
- Vaccines given to healthy people to keep them healthy
Successful programmes protect entire communities and populations
- E.g. eradication of small pox
what 6 vaccines are included in the UK six in one vaccine
Pertussis (whooping cough)
Diphtheria
Tetanus
Polio
Hib
Hepatitis B
pertussis
whooping cough
bacterial disease
tetanus
life threatening muscle spasms
from deep cut/animal bite
booster every 10 years
polio
virus affecting nervous system
- paralysis
- can be asymptomatic
Hib
bacterial – severe infection, sepsis, meningitis, pneumonia
12 diseases protected against by 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)
what is key to national immunisation programmes effectiveness
public trust
need to maintain high % vaccinated in population to keep rates low
vaccines are safe and effective but not completely risk free
- adverse effects can occur
evolution of immunisation
Disease is increasing
Vaccine increase
- Disease fall
Increase in perceived or real adverse events
- public awareness of vaccine diminish
- Not seeing disease thus not aware of risks associated with disease
- Risk of immunisation with vaccine will decrease as cannot see side effects of disease
Outbreaks can increase awareness of disease risk
herd immunity
to have complete protection from exposure need 95% coverage of the vaccine in the population to keep levels low
MMR need 2 doses to be effective
ethical dilemma - should vaccines be made compulsory
- lose autonomy
- protection of greater good
how do vaccines work
Replicate immunity from natural infection without illness
Replicate adaptive immunity and generate long-term immunological memory
induction of protective long term immunity
Epithelial barrier cuts
- Skin, Respiratory tract
Adaptive Immunity
- Engulf pathogen
Degrade it and present bits of pathogen on surface
T cells recognise part of antigen
- Proliferate and different into effective t cells
B cell recognise pathogen
- B activation
- —Make IgM antibodies
- —Non specific
- —Not that effective at clearing infection
Need an activated effector T cell to help B cell
- B cell can differentiate to plasma cell
- Antibody class switching
- —High affinity IgG antibodies
- —Effective at clearing infection
Have small population of long-lived memory cells
- respond immediately next time, not take 7-10 days
induction of highly specific antibody to natural infection is key becuase
No Adaptive immunity
- Time for B cells and IgM
—–Takes longer to get B and T cell talk to have class switching
- Then make IgG
—–Sufficiently high affinity to clear infection
Most plasma cells die - some remain
Production of high affinity IgG cells first is quicker as of innate immune memory
what is the most important goal for vaccination
Production of high affinity IgG represents the most important goal of vaccination
try and generate memory
No adaptive immunity
straight to innate immune memory
primary response by immune system to disease
Low specificity IgM produced first
High specificity IgG takes longer
- Requires T cell help
secondary response by immune system to disease
More rapid
More effective
High specificity IgG produced by long-lived plasma cells
vaccination aims to
reproduce immunity to natural infections without causing disease
vaccination involves
exposing our immune system to disease causing microbial antigens but without causing disease
what are virulence factors
are the molecules expressed by bacteria that help them attach, invade and replicate within our tissues
basically, they are disease-causing factors and these are the bits of microbes that stimulate our immune system
- recognises virulence factors as non-self antigens
and if those virulence factors are conserved structural components – such as bits of Gram negative cell wall (LPS) or Gram positive cell wall (peptidoglycan) or even viral RNA then they are recognised by and activate our innate immune response
but if they specific for a particular pathogen – e.g. a specific receptors expressed by the chicken pox virus or a bacterial toxin – they will activate our adaptive immune response.
So, our immune response has to encounter the disease causing factors in order to mount an immune response
the dilemma then is how to expose the immune system to those disease-causing factors without causing disease
what does our immune response recognise virulence factors as
recognises virulence factors as non-self antigens
how are virulence factors that are conserved structural components recognised as
conserved structural components – such as bits of Gram negative cell wall (LPS) or Gram positive cell wall (peptidoglycan) or even viral RNA
then they are recognised by and activate our innate immune response
what are conserved structural component
such as bits of Gram negative cell wall (LPS) or Gram positive cell wall (peptidoglycan) or even viral RNA
how are virulence factors that are specific to antigens recognised by immune system
specific for a particular pathogen (e.g. a specific receptors expressed by the chicken pox virus or a bacterial toxin)
they will activate our adaptive immune response.
example of virulence factor that are specific to antigens
e.g. a specific receptors expressed by the chicken pox virus or a bacterial toxin
what is the dilemma in designing a vaccine
how to expose the immune system to those disease-causing factors without causing disease
3 types of vaccine
live attenuated
inactivated
subunit (purified antigen)
what are the 4 types of subunit (purified antigen) vaccine
Recombinant
Toxoid
Polysaccharide
Conjugate
live attenuated vaccines
Live but weakened via genetic manipulations
Capable of replication within host cells
Excellent life-long immunity
Potentially pathogenic in immune-compromised
E.g. MMR, BCG, Rotavirus
inactivated vaccines
Killed through chemical or physical processes but still structurally intact
Cannot replicate or cause disease
- safer
Weak immunity
Several doses required - boosters
e.g. Polio, Pertussis
subunit (purified antigens) vaccines
No live components
- Take proteins or peptides
Recombinant – produced by genetic engineering
- Hep B
- HPV
Toxoid – inactivated bacterial toxins
- Diphtheria
- Tetanus
Polysaccharide
Capsule on outside of cell membrane - encapsulated bacteria
- Helps bacteria evade and hide from immune system
T cell-independent – activated not in response to peptides?
Conjugate
- Recruit B cells to talk to T cells to get high IgG
- –polysaccharide antigens linked to proteins
PCV/Hib/Men-C
recombinant subunit (purified antigen) vaccine
produced by genetic engineering
- Hep B
- HPV
toxoid subunit (purified antigen) vaccine
inactivated bacterial toxins
- Diphtheria
- Tetanus
polysaccharide (purified antigen) vaccine
Capsule on outside of cell membrane - encapsulated bacteria
- Helps bacteria evade and hide from immune system
T cell-independent – activated not in response to peptides?
conjugate (purified antigen) vaccine
Recruit B cells to talk to T cells to get high IgG
—polysaccharide antigens linked to proteins
PCV/Hib/Men-C
IgG response to live attenuated vaccines
One dose of vaccine can generate a high specificity IgG response
- Typically still get 2
IgG response to inactivated/subunit vaccines
Weaker immunity
Takes 2 or 3 doses
- For long live memory response
what is an adjuvant
Enhance immune responses to vaccine antigens
Inactivated/subunit vaccines
Aluminium/calcium salts
- Maintain and prolong antigen stability
- Enhance and prolong antigen presentation
- Granuloma formation
Intramuscular delivery
5 routes of vaccine administration
Intramuscular – most common
- Hep B, Hib, PCV-7
Subcutaneous
- measles, yellow fever
Intradermal - scaring
- BCG
Intranasal
Oral
- OPV, rotavirus
background aetiology to dental caries
Bacterial aetiology
Cariogenic bacteria produce acids that demineralise tooth surfaces
- Dietary sugars as energy source
- Ferment by anaerobic metabolism
- Make acid as by product
- Demineralise tooth surface
Mutans streptococci
- Extremely efficient at accumulating and producing carious surfaces
- —Preferred binding site
- —Colonisation stimulates immune system – antibodies made for them
- Extremely tolerant of low pH
- Colonisation coincides with tooth eruption
- Colonisation stimulates specific IgA and IgG
biological considerations for dental caries vaccine (block colonisation of Mutans streptococci)
Mutans streptococci dominate environments frequently exposed to dietary carbohydrates
Mutans streptococci are not the only-cariogenic bacteria in the oral biofilm
- Other cariogenic species are likely to fill niche
ethical considerations for dental caries vaccine (block colonisation of Mutans streptococci)
Non-life threatening condition
Expensive
Other initiatives are more cost-effective
- Childsmile
- Water fluoridation
- Dietary advice
key reason against periodontal disease vaccine
polymicrobial
- Target one could lead to competitive advantage for others to fill niche
what does the decrease in Communicable diseases being main cause of death lead to
increase in aging population
increase in burden of non-communicable diseases
- Cardiovascular diseases
- Cancer
- Metabolic disorders
- Chronic kidney diseases
- Autoimmune diseases
- Neurodegenerative disorders
successful vaccination programmes have contributed to
Decreasing burden of infectious diseases
Increasing burden of NCDs associated with aging
what underlies most chronic diseases that dominate present dat morbidity and mortality
pathological inflammatory pathways
- inflammation responses to infection and other challenges body faces
4 conventional immunosuppressive drugs
Corticosteroids
Non-steroidal anti-inflammatories (NSAIDS)
Methotrexate (DMARDs)
Biological therapies
corticosteroids are
Synthetic versions of cortisol e.g. prednisolone
- stress hormone, released in flight or fight response
Non-specific anti-inflammatory function
corticosteroids effect
Treat wide range of inflammatory/allergic conditions
- Wide spread anti-inflammatory effect
Systemic or topical application
4 side effects of corticosteroids
weight gain
risk of infection
risk of diabetes
risk of hypertension
NSAIDs
non-steroidal anti-inflammatory drugs
ibuprofen, aspirin
mechanism of NSAIDs
Upregulate COX2
Absorbed through stomach
- Take food, don’t take on empty stomach
effects of NSAIDs
Reduce pain, inflammation and fever
Constant use can lead to gastro-intestinal bleeding, liver and kidney problems
Interact with other medications (warfarin, diuretics, methotrexate)
methotrexate aka
Disease-modifying anti-rheumatic drug (DMARD)
high doses of DMARD
chemotherapy agent
low doses of DMARD
inflammatory arthritis treatment
effect of DMARD (methotrexate)
Multi-faceted anti-inflammatory effects
- Often one of first drugs given
Slows progression of arthritis
- Don’t know how they mediate these effects
Can be combined with biological therapies
biological therapies (biologics)
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)
biological therapies (biologics) used for
Moderate to severe RA patients to slow disease progression
May be combined with DMARDs
how many anti TNF therapies are licensed in the UK
5
all work in different ways
- Infliximab binds soluble TNFa
- —Prevent cytokine interacting with receptors – inhibit pathway
- Etanercept binds and blocks TNF receptor
- —Can bind to receptor – inhibit pathway
effect of anti-TNF therapies
Patients can expect at least 20% clinical improvement
- due to inhibition of pathway either at cytokine interacting with receptor or receptor blocked
Often combined with methotrexate
similarities and differenced between RA and periodontitis
both associated with destruction of bone
but perio trigger
- Change in bacterial number or composition; Or gene expression; Or Virulence factors; Or Infection
- —Consequence block inflammatory pathways that are preventing bacteria travelling through body
Rheumatoid - autoimmune
what drives bone destruction in perio?
cytokines
- elevated levels of cytokines in gingival tissues
- Regulate immune-mediated bone destruction
basic aim of vaccination
stimulate adaptive immunity and generate long-term immunological memory
describe simply how vaccination is achieved
exposing our immune system to microbial antigens without causing disease
what are conventional immunosuppressant drugs used to treat
wide-range of conditions
Corticosteroids
NSAIDs
Methotrexate
what do targeted biological therapies do
harness the specificity of antibodies to target and block pathological inflammatory pathways
