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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Autism and vaccines

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Composition of incomplete Freund’s adjuvant

A

Oil-in-water emulsion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Composition of complete Freund’s adjuvant

A

Oil-in-water emulsion w/ dead mycobacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Composition of Freund’s adjuvant w/ MDP

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Composition of alum (aluminum hydroxide)

A

Aluminum hydroxide gel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How to generate attenuated vaccines
- 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
What are conjugate vaccines? What is the difference between this and a free polysaccharide?
- 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
Follicular T-helper cells
- Unique helper T cell population - Have high Ag binding potential - Adjuvants can affect the quantity and quality of Tfh cells
28
Define toxoid and DNA vaccine
- 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
What is thimerosal? What is its function?
- 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