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Basic Immunology > Lecture 15 (9A) - Vaccination > Flashcards

Lecture 15 (9A) - Vaccination Flashcards

1
Q

Edward Jenner

A
  • developed the first vaccine - against smallpox
  • used a related virus (vaccinia) from cows to generate an immune response which cross-reacted against smallpox
  • since 1980 smallpox has been completely eradicated from the world (it’s possible to completely eradicate a dsease(
  • cow - vacca
  • cowpox and smallpox close enough that if given cowpox don’t get smallpox
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2
Q

There are no vaccines for some diseases because

A

they hide from the immune system

- immune can’t get it so (immune) goes away a bit

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3
Q

Vaccines may not work because of

A

mutations/recombinations

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4
Q

Vaccination gives a bigger dip than

A

antibiotics

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5
Q

Vaccination is the

A

success story of medicine

• the principle reason why immunology became important

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6
Q

Features of an effective vaccine

A
  • safety - must not itself cause illness or death
  • protection - must protect against exposure to the pathogen
  • longevity - should give long-lasting protection
  • neutralizing antibodies - must be induced to protect against pathogens such as polio, and many toxins and venoms
  • protective T cells - must be induced to protect against pathogens such as TB
  • practicality - cheap to produce and easy to administer
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7
Q

Herd immunity

A
  • if people are in a place, next to each other = in contact
  • 1 person gets something –> many/most get it
  • don’t need to vaccinate everybody (eg 80%)
  • enough people vaccinated = disease doesn’t spread, no outbreak/epidemic

when the vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immunity

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8
Q

Types of vaccination

A

• active immunization
–> moder vaccines
• passive immunization

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9
Q

Vaccination is

A

active immunization, not passive

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10
Q

Active immunization

A
  • inactivated vaccines (eg heat-treated)
  • attenuated vaccines (a weaker strain eg get antibodies from moms breast milk = babies immune system fights weaker pathogens)

–> modern vaccines

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11
Q

Passive immunization

A
  • receiving antibodies
  • transfer or maternal antibodies from mother to baby

• passive = receiving antibodies
short term protection
not changing immune system - not vaccination
vaccination keeps safe with longevity

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12
Q

Passive imminization - receiving antibodies

process

A
  • inject killed pathogen
  • 10 days later take blood
  • serum from blood (including neutralizing antibodies)
  • give serum to another mouse (transfer of antibodies)
  • challenge with live pathogen = animal survives
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13
Q

Passive immunization

A

• often given to counteract insect/animal venoms (eg spider or snake)
• usually horse serum is used
• there are problems associated with this type of immunization
- the immunization effect lasts for as long as the antibody remains active - a few months at the most
- the patient makes an immune response against the serum (can cause serum sickness)

PASSIVE IMMUNIZATION DOES NOT GIVE LONG-LASTING PROTECTION

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14
Q

Poliomyelitis

A

polio - infantile paralysis
• the child-killer of the 1940-1950s
• Jonas Salk (and slightly later Albert Sabin) both developed an effective vaccine to polio

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15
Q

Jonas Salk’s polio vaccination

A

inactivated vaccine
• the polio virus “marinated” in formalin (pickled)
• the virus is unable to replicate (deactivated)
• the vaccine generates good humoral immunity
• no change of disease (but often adverse side effects)

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16
Q

Albert Sabin’s polio vaccination

A

Attenuated vaccine
• a live weakened polio virus was generated (from guinea pigs)
• the virus can replicate but doesn’t cause disease
• the vaccine generates both humoral and cell-mediated immunity
• occasional polio in vaccinated patients

17
Q

Salk v Sabin

A
  • Salk = injection
  • Sabin = sugar lump
  • Salk - pickled polio (killed)
  • Sabin - didn’t kill it but attenuated - grew in guinea pigs, got less virulent = doesn’t cause disease but get response

• polio is in gut (water)
sugar lump goes and acts in gut, replicates inside you, better immune response

  • Salk –> Sabin –> Salk
  • Salk safer, people get injection, polio decreased
  • Salk infected with no symptoms but can pass on (no symptoms but have polio)
  • Sabin clears because polio in sugar in same path (to gut), better gut response, rids polio
18
Q

Inactivated vaccine

A

DC has MHC-I and MHC-II inside
• formalin treated viral particles go in, don’t cause infection
• present the viral particles on MHC-II

• viral peptide on MHC-II which generates a good CD4+ T cell response –> good antibody production via TH2 CD4+ T cells

(no good on CD8)

19
Q

Attenuated vaccine

A
  • attenuated viral particles do infect cell
  • to nucleus, make viral proteins
  • display viral proteins on surface in both MHC-I and MHC-II
  • viral peptide on MHC-II and MHC-I which generates a good CD4+ and CD8+ T cell response, hence good antibody production and T cell mediated cytotoxicity
20
Q

Inactivated vaccines

A 
require neutralizing antibodies
• diptheria
• whooping cough
• tetanus
(^3 = DPT)
• polio (Salk)
• cholera
• influenza
• plague
• rabies (now attenuated)
21
Q

Attenuated vaccines

A 
require neutralizing antibodies and a cell-mediated response
• measles
• mumps
• rubella
(^MMR)
• polio (oral - Sabin)
• chicken pox
• tuberculosis (BCG)
• influenza
• yellow fever
• rabies
22
Q

Recombinant peptide vaccines

A

eg Hepatitis B
• this method does NOT use the whole pathogen - reducing risk of side effects

• a specific gene is removed from the virus/pathogen
• gene is added to a culture of yeast
• a single purified viral protein is used for the vaccine
• mixed with adjuvant
–> vaccine

genes cut out, put into vector, get genes to make proteins and use proteins to make vaccine
• how does it know the gene is from protein (of pathogen?)
• adjuvant - protein + pathogen product that tricks immune system into thinking its part of a pathogen
• adjuvant tricks the DC (onto MHC- mostly II) but no B7 or CD40 (no costimulatory molcules)
- adjuvant tricks DC into thinking pathogenic infection

23
Q

The use of adjuvants to make a vaccine immunogenic

A

adjuvants trick the immune system into thinking that there is an infection

• most purified antigens are not strongly immunogenic
eg tetanus toxoid not immunogenic
but
tetauns toxoid + aluminum salts (an adjuvant) = immunogenic (elicits antibodies)

purified viral protein to DC
• no adjuvant = only MHC on DC surface
• with adjuvant (+ cytokines like IL-12) = costimulatory as well (B7, CD40)
==> activates naive T cells

24
Q

Adjuvants

A

trick the immune system into thinking that there’s an infection
• bias toward TH2 antibody response
• stimulate mucosal immunity (eg using pertussis toxin or cholera toxin)
• bias toward TH1 cell-mediated responses (eg using IL-12)
• activate (B7 etc) dendritic cells (and other APC)

25
Q

Considerations for vaccine design

A

whole pathogens or recombinant protein?

  • live attenuated or inactivated vaccine
  • which protein to use? does it elicit protective immunity?

does the vaccine require an adjuvant?

  • which adjuvant (does the adjuvant promote the correct type of immunity ie cell-mediated or antibody)
  • which vaccination route? mucosal (like most infections)? or injection (unlike most infections)

are booster vaccinations required?
can the vaccine be target to certain APC?

safety + cost

26
Q

Modern vaccines - DNA vaccines

A
  1. virus - a specific gene is isolated from the pathogen
  2. the gene is placed in a bacterial plasmid vector (bacterial DNA acts as an adjuvant via TLR9)
    • cytokines?
      (inflammation - good immune response)
  4. the plasmid is injected into the muscle of a recipient
    • DC takes up plasmid, expressed gene and acts as adjuvant –> DC activated
  5. viral challenge
    –> animal is protected

in trials for malaria and HIV

27
Q

The future - therapeutic vaccines

A

an animal is already infected and cannot clear the infection (eg herpes simplex-2 or certain papilloma viruses)
• the sick animal is vaccinated to boost the immune response to the infection
(boosts w/ longevity - vaccine)
== the animal can now clear the infection

28
Q

Cure vs vaccine

A

cure acts directly on the pathogen

vaccines deal with the immune system

Basic Immunology (15 decks)

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