Lecture 11 Flashcards
What is active immunisation
Manipulating the immune system to generate a persistent protective response against pathogens.
Immunisation with a vaccine can trigger an immune response and safely mimic natural infection
Mobilise the appropriate arms of the immune system and generate immunological memory
What’s natural passive immunity and what does it provide protection against
Occurs naturally by the transfer of maternal antibodies across the placenta to the developing foetus.
Diptheria, tetanus, streptococcus, rubella, mumps, poliovirus
What’s the major hazard with passive immunity
Not the primary infection itself (can be eliminated by innate immunity) but the effects of potent toxins released by bacteria e.g. teanus and botulinum
What’s the most commonly used deactivated toxin derivative (toxoid)
Tetanus toxoid
Advantages of passive immunisation
- Use of the preformed antibodies can quickly neutralise toxins and venoms
- A conventional immune response may be too slow
- In the case of highly virulent pathogens, pre formed antibodies isolated or engineered from immunised animals may be the only means of treatment
- In some cases, antibodies from surviving patients can be used
What are the drawbacks of passive immunisation
- Does not activate immunological memory
-No long term protection
-Possibility of reaction to anti-sera
What are the different vaccines
-Whole organism (live attenuated pathogen or killed inactive pathogen)
-Subunit toxoids (antigenic extracts, recombinant proteins, conjugate vaccines)
-Peptides
-DNA vaccines
-Engineered virus
Features of a live attenuated vaccine (whole organism)
The pathogen is altered/ treated to reduce virulence ( for example by adaptation after prolonged cultivation in special medium)
The organism is used in a weakened form
It’s stable to replicate but at a reduced rate
Can produce a short-lived infection but can be cleared by the host without harmful outcome
Features of an inactivated organism (whole organism) vaccine
- The organism is rendered inactive and non-viable by heat, chemical or other treatments.
- Cannot replicate
Advantages of live attenuated vaccines
- Attenuated pathogens sets up a transient infection
-Activation of full natural immune response
-Prolonged contact with the immune system
-Stimulation of a memory response in the T and B cell compartments results in prolonged comprehensive protection
Often only a single immunization is required which is advantageous for third world countries
Disadvantages of live attenuated vaccines
Immunocompromised patients may become infected as a result of immunization.
Complications such as the live measles vaccines
The attenuated organism can revert to a virulent form for example polio sabio - could leads to a serious outbreak in poor areas
Live organisms need to be refrigerated for stable storage- issue for remote areas
Advantages of inactivated pathogens
- No risk of infection
- storage is less critical
-Wide range of different antigenic components are present so good immune response is possible
Disadvantages of inactivated pathogens
- Tend to just activate humoral responses
-Lack of T cell involvement
-Without transient infection, the immune response can be weak
-Repeated booster vaccinations required
-Adjuvents can be used to increase the immune response
-Patient compliance can be an issue
Examples of inactivated vaccines
Bacterial: anthrax, cholera, pertussis, plague
Viruses: Hepatitis A, influenza, polio, rabies, rubella
What are the 3 major types of subunit vaccines
Inactivated exotoxins (toxoids)
Capsular polysaccharides
Recombinant microbial antigens
What are capsular polysaccharides
Capsular PSs are highly polar, hydrophilic cell surface polymers consisting of oligosaccharide repeating units. These molecules are the main antigens involved in the protective immunity to encapsulated bacteria
What do capsular polysaccharides interfere with
Bacterial interactions with phagocytes by blocking opsonization
What’s opsonisation
The coating of the organisms by specific antibodies and complement which enables host phagocytes to inject and destroy invading bacteria
Advantages of synthetic peptides as antigens
-Safety
-Only portions of pathogen are used
- No risk of infection
- May be easier to store and preserve
Disadvantages of synthetic peptides as antigens
- Immune response is less powerful than to live attenuated vaccines
-Repeat vaccinations needed and adjuvants
What is an adjuvant
Any substance added to stimulate the immune response
What can adjuvants include
- Whole killed organisms
-Toxoids
-Proteins (Conjugate vaccines)
-Chemicals
-Aluminium salts
-Oil emulsions
What can aluminium salts do
Extend the half life of immunoglobulin in the site of injection (depot effect)
Chemicals can cause irritation and inflammation
What do toxoids trigger and do
They trigger out the immune system and send out danger signals, acting as delivery systems and immune stimulators
Examples of adjuvants used in humans
Alum (dominant)
Oil/ water emulsions
Detoxified bacterial lipopolysaccharide
Cytokines
Toll-like receptor agonists
What safety hazards can be accompanied from high efficiency
- Risk of autoimmunity
- Chronic inflammation
What’s the aim of DNA vaccines
To transiently express genes from pathogens in host cells and generate immune responses similar to natural infection leading to T and B cell memory responses
Advantages of DNA vaccines
They do not require complex storage and transportation.
Delivery can be simple and adaptable to widespread vaccination programs “DNA gun”
Disadvantages of DNA vaccines
- No transient infection
-DNA vaccination is likely to produce a mild immune response and require subsequent boosting
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What are RNA vaccines
- Similar to DNA vaccines
- Can be designed to encode speciifc antigens
-Injection into cells leads to transient expression of antigen.
What’s the aim of recombinant vector vaccines
- Imitates the effects of transient infections with pathogens but using a non-pathogenic organism
Genes for major pathogens are introduced into a non-pathogenic or attenuated microorganism and introduced into the host
Advantages of recombinant viral vaccines
Creates ideal stimulus to immune system
Produces immunological memory
Flexible (different components can be engineered)
Safe (relative to live attenuated pathogen)
Drawbacks of recombinant viral vaccines
- Requrie refrigeration for transport
-Can cause illness in compromised individuals
- Immune response to virus in subjects can negate effectiveness
What is an ideal vaccine
- Safe
-Should induce a suitable response (for example, mucosal)
-High antibody titer
-Generates T and B cell memory - Is stable and easy to transport
-Should not require repeated boosting
-Patient compliance
