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Immune Therapies Flashcards

1
Q

what is the main reason for immune therapies

A

therapeutic benefit

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2
Q

what 3 things promote protective immune responses

A

vaccination

fight tumours

treat immunocompromised patients

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3
Q

what conventional and targeted immune therapies are used to suppress unwanted immune responses

A

chronic inflammation

autoimmunity

allergy

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4
Q

4 reasons why we vaccinate

A

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

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5
Q

what 6 vaccines are included in the UK six in one vaccine

A

Pertussis (whooping cough)

Diphtheria

Tetanus

Polio

Hib

Hepatitis B

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6
Q

pertussis

A

whooping cough

bacterial disease

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7
Q

tetanus

A

life threatening muscle spasms

from deep cut/animal bite

booster every 10 years

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8
Q

polio

A

virus affecting nervous system

  • paralysis
  • can be asymptomatic
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9
Q

Hib

A

bacterial – severe infection, sepsis, meningitis, pneumonia

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10
Q

12 diseases protected against by UK vaccination programme

A

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)

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11
Q

what is key to national immunisation programmes effectiveness

A

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

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12
Q

evolution of immunisation

A

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

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13
Q

herd immunity

A

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
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14
Q

how do vaccines work

A

Replicate immunity from natural infection without illness

Replicate adaptive immunity and generate long-term immunological memory

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15
Q

induction of protective long term immunity

A

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

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16
Q

induction of highly specific antibody to natural infection is key becuase

A

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

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17
Q

what is the most important goal for vaccination

A

Production of high affinity IgG represents the most important goal of vaccination
try and generate memory

No adaptive immunity
straight to innate immune memory

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18
Q

primary response by immune system to disease

A

Low specificity IgM produced first

High specificity IgG takes longer
- Requires T cell help

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19
Q

secondary response by immune system to disease

A

More rapid

More effective

High specificity IgG produced by long-lived plasma cells

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20
Q

vaccination aims to

A

reproduce immunity to natural infections without causing disease

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21
Q

vaccination involves

A

exposing our immune system to disease causing microbial antigens but without causing disease

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22
Q

what are virulence factors

A

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

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23
Q

what does our immune response recognise virulence factors as

A

recognises virulence factors as non-self antigens

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24
Q

how are virulence factors that are conserved structural components recognised as

A

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

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25
what are conserved structural component
such as bits of Gram negative cell wall (LPS) or Gram positive cell wall (peptidoglycan) or even viral RNA
26
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.
27
example of virulence factor that are specific to antigens
e.g. a specific receptors expressed by the chicken pox virus or a bacterial toxin
28
what is the dilemma in designing a vaccine
how to expose the immune system to those disease-causing factors without causing disease
29
3 types of vaccine
live attenuated inactivated subunit (purified antigen)
30
what are the 4 types of subunit (purified antigen) vaccine
Recombinant Toxoid Polysaccharide Conjugate
31
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
32
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
33
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
34
recombinant subunit (purified antigen) vaccine
produced by genetic engineering - Hep B - HPV
35
toxoid subunit (purified antigen) vaccine
inactivated bacterial toxins - Diphtheria - Tetanus
36
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?
37
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
38
IgG response to live attenuated vaccines
One dose of vaccine can generate a high specificity IgG response - Typically still get 2
39
IgG response to inactivated/subunit vaccines
Weaker immunity Takes 2 or 3 doses - For long live memory response
40
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
41
5 routes of vaccine administration
Intramuscular – most common - Hep B, Hib, PCV-7 Subcutaneous - measles, yellow fever Intradermal - scaring - BCG Intranasal Oral - OPV, rotavirus
42
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
43
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
44
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
45
key reason against periodontal disease vaccine
polymicrobial | - Target one could lead to competitive advantage for others to fill niche
46
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
47
successful vaccination programmes have contributed to
Decreasing burden of infectious diseases Increasing burden of NCDs associated with aging
48
what underlies most chronic diseases that dominate present dat morbidity and mortality
pathological inflammatory pathways | - inflammation responses to infection and other challenges body faces
49
4 conventional immunosuppressive drugs
Corticosteroids Non-steroidal anti-inflammatories (NSAIDS) Methotrexate (DMARDs) Biological therapies
50
corticosteroids are
Synthetic versions of cortisol e.g. prednisolone - stress hormone, released in flight or fight response Non-specific anti-inflammatory function
51
corticosteroids effect
Treat wide range of inflammatory/allergic conditions - Wide spread anti-inflammatory effect Systemic or topical application
52
4 side effects of corticosteroids
weight gain risk of infection risk of diabetes risk of hypertension
53
NSAIDs
non-steroidal anti-inflammatory drugs ibuprofen, aspirin
54
mechanism of NSAIDs
Upregulate COX2 Absorbed through stomach - Take food, don’t take on empty stomach
55
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)
56
methotrexate aka
Disease-modifying anti-rheumatic drug (DMARD)
57
high doses of DMARD
chemotherapy agent
58
low doses of DMARD
inflammatory arthritis treatment
59
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
60
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)
61
biological therapies (biologics) used for
Moderate to severe RA patients to slow disease progression May be combined with DMARDs
62
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
63
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
64
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
65
what drives bone destruction in perio?
cytokines - elevated levels of cytokines in gingival tissues - Regulate immune-mediated bone destruction
66
basic aim of vaccination
stimulate adaptive immunity and generate long-term immunological memory
67
describe simply how vaccination is achieved
exposing our immune system to microbial antigens without causing disease
68
what are conventional immunosuppressant drugs used to treat
wide-range of conditions Corticosteroids NSAIDs Methotrexate
69
what do targeted biological therapies do
harness the specificity of antibodies to target and block pathological inflammatory pathways

BDS2 BAMS (54 decks)

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