Respiratory Immunology 5: Vaccination Flashcards
What is vaccination, why is it done and how is the effect achieved?
Deliberate exposure to an antigen in order to induce immunologically mediated resistance to disease, through induction of memory
Generation of immunological memory?
Stimulation and maturation of the immune response after exposure to an antigen, such that is able to respond immediately and robustly upon re-exposure
Generation of memory B cells?
Long-lived MEMORY B CELLS are generated during primary humoral immune responses
Memory B cells can survive in a dormant state for many years after antigen has been eliminated
Memory B cells rapidly re-activate in response to a second encounter with that specific antigen - clonal expansion, differentiation into plasma cells, antibody production
Impact of memory on antibody production?
Primary infection - during incubation period, IgM antibody being produced and IgG antibody is produced later on, towards the end of clinical disease presentation
Secondary infection - IgG antibody produced immediately due to memory B cells and so clinical features do not present
Describe secondary antibody response
Pre-existing IgG antibody results in ability to clear during incubation periods:
Direct action to neutralise bacteria and bacterial products
Rapid mobilisation of phagocytes and complement
Pre-formed IgA blocks bacterial attachment to mucous membranes`
Clearing of toxin in Diphtheria?
Individual may clear toxin through anti-toxin antibodies, but remain a carrier of micro-organism
How is T cell memory generated through vaccination?
Vaccination simulates rare naive T cells and induces a strong T cell response in 14-21 days; some become EFFECTOR T cells which:
Mostly die by apoptosis in absence of persisting antigen
Smaller number become MEMORY CELLS and are maintained at low frequency
Memory T cell characteristics?
Make a MORE EFFECTIVE IMMUNE RESPONSE:
Primed CD8 T cells can immediately kill without immunological “help”
Primed CD4 T cells can produce cytokines immediately
Have enhanced properties of cell adhesion and chemotaxis - memory cells can access non-lymphoid tissues effectively, where bugs actually are
LONGEVITY - memory T cells can be maintained for a long time without antigen
How long does memory last?
A long time - e.g: re-exposure to measles virus is unnecessary in maintaining memory
Types of vaccination?
Difference between immunisation and vaccination?
Immunisation - process through which an individual develops immunity/memory to a disease (inc. both deliberate and natural infection)
Vaccination - deliberate administration of antogenic material to produce immunity to a disease
What is active immunity?
Protection produced by the person’s own immune system; can be stimulated by vaccine/naturally acquired infection and is usually permanent
What is passive immunity?
Protection transferred from another person or animals but is temporary and wanes with time
Describe active vaccination
Stimulates immune response to antigen through SAME PATHWAYS AS NATURAL INFECTION; thus generates immunity and memory similar to natural infection
MORE SIMILAR A VACCINE IS TO DISEASE-CAUSING FORM OF ORGANISM, BETTER THE IMMUNE RESPONSE TO DISEASE IS
Methods for generating immunological memory?
Exposure of an individual to INFECTIOUS ORGANISM ITSELF
Exposure to a SIMILAR PATHODEN that is LESS VIRULENT
Exposure to the INACTIVATED PATHOGEN
Exposure to a LESS VIRULENT VERSION of the SAME PATHOGEN
What is variolation?
Predecessor of vaccination - exposure to contents of dried smallpox pustules from infected patient, optimally from people with less severe disease 1:100 died
Principle of exposure to a similar but less virulent pathogen?
One disease is being induced to generate cross-reactive immunity against another disease
Example of exposure to a similar but less virulent pathogen?
Immunisation with cowpox protecting against smallpox as:
Molecular similarities between cowpox and smallpox
Antibodies generated through exposure to cowpox cross-react with smallpox, neutralising the smallpox virus
Inactivated vaccines AKA?
ATTENUATED or killed (not a good term as some inactivated vaccines are made from components and were not alive before) vaccines
Key features of inactivated vaccines?
Cannot replicate but generally not as effective as live vaccines
Immune response PRIMARILY ANTIBODY-BASED (not T cells); antibody titre may diminish with time and may require MULTIPLE DOSES to stimulate immune response
How to make an inactive vaccine from a live pathogen?
Expose pathogen to chemical fixative, e.g: formalin, heat denaturation or irradiation
Problems with inactive vaccines?
Under-activation - leaves viable pathogens/toxins within organism
Over-activation - loss of tertiary structure and conformational antibody binding sites
What is poliomyelitis?
Caused by POLIO VIRUS, which is transmitted via oro-faecal route
Clinical presentation of poliomyelitis?
90-95% of infections are asymptomatic - may still transmit disease
5% have minor flu-like illness
0.5% cases develop muscle weakness and paralysis - may develop post-polio syndrome
Describe polio vaccine
Sabin Polio vaccine - LIVE ATTENUATED polio virus strains. Unsafe in immunocompromised host
Advantages of inactivated vaccines?
Can be made quickly, prevent epidemics
May elicit good antibody responses
Easy to store - no refrigeration required USUALLY safe - can be given to immunocompromised individuals
Disadvantages of inactivated vaccines?
May be difficult to stimulate an immune response to many killed organisms - does not replicate of disseminate and often require ADJUVANTS to improve immunogenicity
Poor at eliciting T cell responses
Memory variable - requires multiple injections, booster immunisation requries
What are adjuvants?
Mixture of inflammatory substances required to stimulate immune responses (co-administered peptides, proteins or carbohydrates)
Other pathogens - like Bordetella pertussis
Why do adjuvants work?
Create inflammatory environment:
Bind to macrophages and signal the unequivocal presence of a microbial invader
Activate innate immune system to stimulate development of antibody and T cell responses
Problems with adjuvants?
Toxic
Alter the immune response - generated to vaccine:protein conjugates rather than vaccine itself CD4+ T cells may recognise the carrier only; thus, infection challenge will not necessarily elicit a secondary response
Types of inactivated vaccines?
Whole cell vaccines, i.e: whole organism used
Fractional vaccines - only part of the organism used in the vaccine:
Sub-unit vaccines
Pure polysaccharide vaccines
Describe the Hep B vaccine
First of the anti-cancer vaccines - protects against Hep B associated hepatocellular cancer
Describe polysaccharide vaccines
Polysaccharide sugars from the outer capsule of some bacteria determines pathogenicity and antigenicity but they are not good at stimulating responses (generates antibody with less functional activity, esp. in immature immune system)
Immunogenicity can be improved by conjugating to an adjuvant (CONJUGATE VACCINES)
What are live attenuated vaccines?
Less virulent version of the same pathogen Attenuated/weakened form of “wild” virus/bacterium; the immune response is similar to natural infection Organism must replicate to be effective and usually generates immunity with single dose
Examples of live attenuated vaccines?
Viruses - measles, mumps, rubella, chickenpox Bacterial - BCG
Advantages of live attenuated vaccines?
Very similar to natural infection, so relevant effector mechanisms elicited (antibody, activated T cells)
Localised, strong response
Memory good so boosting not usually required
Disadvantages of live attenuated vaccines?
Immune response can be interfered with by circulating antibody
Safety - may require new mutations and revert to virulence, e.g: vaccine-associated poliomyelitis, and MAY CAUSE INFECTION IN IMMUNOCOMPROMISED HOST
Fragile - must be stored and handled carefully, i.e: depends on cold chain
Example of naturally acquired passive immunity?
Transplacental transfer of antibody
Describe transplacental transfer of antibody and in breast milk
Maternal antibody is crucial to protection of infant in 1st 6 months of life; there is active transport of maternal IgG in 3rd trimester;
Via breast milk, esp. colostrum, containing IgA (important for colonisation of infant GI tract)
Maternal antibody also important in enabling subsequent memory - exposure to an antigen while under cover of maternal antibody may result in a less severe illness but memory to antigen is generated
Examples of therapeutic passive immunisation?
Pooled normal human immunoglobulin
Monoclonal antibody against specific pathogen
What is pooled immunoglobulin?
Transfer of antibody from an unrelated individual:
Pooled normal immunoglobulin from immune humans - used for protection from Hep A
Hyperimmune globulin - administered after specific exposure; immunoglobulin from an individual known to have high antibody levels against a specific pathogen (rabies - post exposure, snake venom anti-toxin)
Describe passive immunisation with monoclonal antibodies for Respiratory Syncitial Virus and what the indications are
Palivizumab - monoclonal antibody produced against a single determinant of Respiratory Syncitial Virus (RSV)
Indications - prevention of severe LRT infections in high-risk infants (may have severe congenital heart disease; pre-term infants, severe chronic lung disease
Organisms difficult to create vaccines against?
Chronic or latent infections - immune system does not normally generate a response that clears organisms, e.g: TB, Hep B, HIV, herpes viruses)
Rapidly evolving infections - pathogens highly adept at immune evasion, e.g: HIV, Influenza
Cancer preventative vaccines?
Hep B HPV
Describe addiction vaccines
Drugs of abuse are small molecule and readily cross blood-brain barrier
Addiction vaccines aim to reduce drug levels in the brain - stimulate antibody which binds to drug before it enters brain so cannot cross barrier
