3 - Vaccines Flashcards

1
Q

Vaccine side effects

A
  • Inflammation and anaphylactic reactions
    • Contaminates in vaccine preparation (ex: egg proteins in flu vaccine; mercury containing preservatives)
  • Infection
    • Improperly inactivated vaccine preparations
    • Use of a live-attenuated vaccine in immune-deficient px
  • Neurological and autoimmune reactions
    • Caused by rare antigen cross reactions or perturbation of immuno-regulatory circuits
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2
Q

Autism and vaccines

A

Has been hypothesized that autism is induced by heavy metal poisoning associated w/ vaccination (thimerosal)

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3
Q

Vaccine immunology – innate immunity

A
  • Comprises the cells and mechanisms that defend the host from infection by other organisms
  • Cells of innate system recognize and respond to pathogens in a generic way
  • Doesn’t provide long-lasting immunity to the host
  • Innate immune systems provide immediate defence against infection
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4
Q

Vaccine immunology – adaptive immunity

A
  • Composed of highly specialized, systemic cells and processes that eliminate pathogens or prevent their growth
  • Creates immunological memory after initial response to a specific pathogen, and leads to an enhanced response to subsequent encounters w/ that pathogen
  • Process of acquired immunity is the basis of vaccination
  • Includes humoral immunity and cell-mediated immunity
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5
Q

Vaccine immunology

A
  • Vaccines protect by inducing effector mechanism (both cells and molecules)
  • Different components of vaccines induce different effector mechanism
    • Capsular polysaccharides elicit B-cell response as T-independent manner
    • Conjugation of bacterial polysaccharides to a protein carrier provides peptide antigens, which recruit antigen-specific CD4+ Tfh cells (kind of T-helper cell) as a T-dependent antibody response
    • Protein antigens such as live attenuated vaccines generate CD8+ cytotoxic T cells
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6
Q

Effector mechanisms triggered by vaccine – antibody functions

A
  • Prevent and reduce infections by clearing extracellular pathogens through:
    • Binding to the enzymatic active sites of toxins or preventing their diffusion
    • Neutralizing viral replication by preventing viral binding and entry into cells
    • Enhancing extracellular bacteria clearance by macrophages and neutrophils
    • Activating the complement cascade
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7
Q

Effector mechanisms triggered by vaccine – CD8+ T cells function

A
  • Don’t prevent infection, but reduce, control, and clear intracellular pathogens by:
    • Directly killing infected cells by release of perforin, granzyme, etc.
    • Indirectly killing infected cells through antimicrobial cytokine release
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8
Q

Effector mechanisms triggered by vaccine – CD4+ T cells function

A
  • Don’t prevent infection but participate in reduction, control, and clearance of extracellular and intracellular pathogens by the homing and cytokine production capacities
  • Main subsets include:
    • Follicular T-helper cells (Tfh) producing mainly interleukin (IL) 21 and providing B-cell help
    • T-helper 1 (Th1) effector cells producing interferon gamma, tumour necrosis factor alpha, and IL-2, and mainly involved in protection against intracellular pathogens (viruses)
    • Th2 effector cells producing IL-4, IL-5, IL-13 and responding to extracellular pathogens (bacteria)
    • Th17 effector cells producing IL-17, IL-22, IL-26, and contributing mucosal defence (streptococcus pneumoniae)
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9
Q

Initiation of a vaccine response

A
  • Pathogen-associated pattern contained in vaccine antigens attract dendritic cells, monocytes, and neutrophils that control throughout the body
  • Stimulation of sufficient “danger signals” by the vaccine antigens/adjuvants activate monocyte and dendritic cells
  • Activation changes their surface receptor and induces migration along lymphatic vessels to the draining lymph nodes
  • In the lymph nodes, T and B lymphocytes are activated
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10
Q

Types of vaccines

A
  • Killed pathogen – heat or formalin killed pathogen (ex: Salk polio vaccine)
  • Live-attenuated – selection of less or non-pathogenic variants (ex: Sabin polio vaccine)
  • Subunit vaccine – purified or genetically engineered structural component of a pathogen (ex: hep B vaccine)
  • Conjugate vaccines – combination of multiple components to increase immunogenicity or memory induction
  • Secreted or extracted bacterial products – toxoids or cell wall polysaccharides
    • Toxoids are toxins inactivated by chemical treatment or induced mutation to be immunogenic but not pathogenic toxins
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11
Q

Features of effective vaccines

A
  • Safe – vaccine must not cause illness or death itself
  • Protective – must protect against illness resulting from exposure to live pathogen
  • Gives sustained protection – protection against illness must last for several years or lifelong
  • Induces neutralizing antibody – some pathogens (ex: poliovirus) infect cells that cannot be replaced (ex: neurons); neutralizing antibodies are essential to prevent infection of such cells
  • Induces protective T cells – some pathogens are more effectively dealt w/ by cell-mediated responses particularly intracellular pathogens
  • Practical considerations – low cost per dose, biological stability, ease of administration, few side effects
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12
Q

Composition of incomplete Freund’s adjuvant

A

Oil-in-water emulsion

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13
Q

Composition of complete Freund’s adjuvant

A

Oil-in-water emulsion w/ dead mycobacteria

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14
Q

Composition of Freund’s adjuvant w/ MDP

A

Oil-in-water emulsion w/ mutamyl dipeptide (MDP) – a constituent of mycobacteria

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15
Q

Composition of alum (aluminum hydroxide)

A

Aluminum hydroxide gel

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16
Q

Composition of alum + bordetella pertussis

A

Aluminum hydroxide gel w/ killed B pertussis

17
Q

Composition of immune stimulatory complexes (ISCOMs)

A

Matrix of Quil A (saponin adjuvant) containing viral proteins

18
Q

MOA of incomplete Freund’s adjuvant

A

Delayed release of Ag, enhanced uptake by macrophages

19
Q

MOA of complete Freund’s adjuvant

A

Delayed release of Ag, enhanced uptake by macrophages, induction of co-stimulators in macrophages

20
Q

MOA of Freund’s adjuvant w/ MDP

A

Similar to complete Freund’s adjuvant

21
Q

MOA of aluminum hydroxide

A

Delayed release of Ag, enhanced macrophage uptake

22
Q

MOA of alum + bordetella pertussis

A

Delayed release of Ag, enhanced uptake by macrophages, induction of co-stimulators

23
Q

MOA of immune stimulatory complexes (ISCOMs)

A

Delivers Ag to cytosol, allow induction of cytotoxic T-cells

24
Q

Various aspects of vaccine development

A
  • Inactive or killed vaccine – vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then killed using a method such as heat or formaldehyde
  • Live or attenuated vaccine – vaccine uses pathogens that are still active but are almost attenuated or weakened
25
Q

How to generate attenuated vaccines

A
  • Viruses may be attenuated via passage of the virus through a foreign host, such as:
    • Tissue culture
    • Embryonated eggs
    • Live animals
  • Isolate virus in human cells -> infect non-human cells -> virus mutates to grow well in non-human cells -> attenuated virus no longer grows well in human cells
26
Q

What are conjugate vaccines? What is the difference between this and a free polysaccharide?

A
  • Conjugate vaccines – created by covalently attaching a poor Ag to a strong Ag to elicit a stronger immunological response to the poor Ag
  • In most cases, the poor Ag is a polysaccharide that is attached to a strong protein Ag
  • However, peptide/protein and protein/protein conjugates have also been developed
  • Free polysaccharide = short duration of Ab response, no memory, no affinity maturation, no response in young infants (< 18 months)
  • Conjugate = long duration of Ab response, memory, affinity maturation, protective response in young infants (> 2 months)
27
Q

Follicular T-helper cells

A
  • Unique helper T cell population
  • Have high Ag binding potential
  • Adjuvants can affect the quantity and quality of Tfh cells
28
Q

Define toxoid and DNA vaccine

A
  • Toxoid: inactivated part of virus or bacteria, similar process to production of inactivated or killed vaccine
  • DNA vaccine: uses recombinant DNA technology to introduce gene of Ag into DNA expression vector, and then introduce recombinant DNA expression vector into human or cells
29
Q

What is thimerosal? What is its function?

A
  • Thimerosal is a mercury containing compound used as a preservative in DTP, MMR, and other vaccines
  • Thimerosal contains ethylmercury, which prevents growth of bacteria in vaccines and can be eliminated from the body easily