Vaccination and Immunisation Flashcards
what is variolation
a method of inoculation first used to immunise individuals against smallpox by rubbing powdered smallpox scabs on skin or blowing powder up nostrils
describe Jenners findings about how cowpox can protect against smallpox
- first demonstration of cross protection using a related, live virus
- antigens on cowpox induce memory B cells
- on recall, these secrete antibodies that protect both cowpox and smallpox
describe the role of Louis Pasteur
- developed process of pasteurization
- developed vaccines against anthrax and rabies
outline Louis Pasteurs first study
- noted that repeated cultures of Pasteurella lost ability to cause disease
- bacteria had become weakened
- immunised chickens with attenuated pasteurella were resistant to virulent strain
- first lab developed vaccine
outline Pasteurs second study
- repeatedly cultured bacillus anthracis and immunised sheep with attenuated strain
- immunised sheep became resistant to the virulent strain
- attenuated bacillus anthracis also effective in humans
outline Pasteurs third study
- passaged rabies virus from dogs into brain of rabbits
- immunised dogs and protected them against virulent rabies
- created an inactivated vaccine
what is the difference between attenuated and inactivated vaccines
- attenuated means live vaccine
- inactivated means dead vaccine
define immunity
ability of the human body to protect itself from infectious disease
what are the 2 main groups of defence mechanisms in the body
- innate- non specific and non adaptive mechanisms
- acquired- specific, adaptive mechanisms
describe the strategy of immune defence
- block infection by utilising barriers to entry- skin, tears, stomach acid, mucus
- destroy invaders- initially by components of innate immune system (Natural killer cells, phagocytic cells)
- if that fails, trigger adaptive immune system- antigen presenting cells activate T helper cells
what are the 2 basic mechanisms for acquired immunity
- active
- passive
what is active acquired immunity
- produced by individuals own immune system- usually long lasting
- involves cellular responses and humoral responses
- can be acquired by natural disease or by vaccination
what occurs in CD4 lineage in the adaptive immune system
- bacterial pathogen is presented to antigen presenting cells
- APCs present it as peptides with MHCII to naive CD4 T helper cells
- which become effector T cells of 4 basic types
what occurs in CD8 lineage in the adaptive immune system
- APCs (dendritic cells) see antigen and present it with MHCI to naive CD8+ cells
- CD8+ cells become cytotoxic T cells which produce cytotoxins or trigger apoptosis of the target cell
- to continue cytotoxic T cell production and create memory cells, APC must interact with activated CD4 T helper cell
what are humoral responses
antibody mediated immunity
how does antibody provide immunity against infection
- blocking binding of pathogen to cell surface receptors- neutralising antibodies
- targeting CTLs to infected cells
- coating pathogens and targeting them for phagocytosis
- antibody antigen complexes activate classical complement cascade which leads to destruction of pathogens by phagocytosis or bacterial membrane attack
what is cell mediated immunity provided by
effector lymphocytes (T cells) of T helper cells
what are the 2 principle classes of cell mediated immunity
- CD8+ T cells- recognise and destroy infected cells
- CD4+ Th1 T cells- activate phagocytic macrophages to destroy and engulf bacteria
how do Th1 cells activate macrophages
by cytokines
what is the role of IgM
major role in complement activation
- limited role in neutralisation
- induced by vaccination
what is the role of IgG
- systemic
- all major roles: neutralisation, ADCC, opsonisation and complement activation
- primarily induced by vaccination
what is the role of IgA
- principle isotype in secretions at mucosa
- less potent opsonisation, weak activator of complement
- strong viral neutraliser
- can be induced by vaccination but needs specific adjuvant
what is passive immunity
protection provided by transfer of antibodies from mother, most commonly across the placenta (IgG) and breast milk (IgA) to child
which vaccines should pregnant women be offered and why
- pertussis- most infant deaths from pertussis at less than 3 months old
- rubella- can severely damage foetus, so mother offered MMR if not previously vaccinated
- influenza- pregnant women have increased risk of death if not vaccinated
how long does protection provided by MTC transfer last
temporary- few weeks or months
- neonate (1-28 days) is very vulnerable to disease and protected by maternal antibodies
how do vaccines produce their protective effect
by inducing active acquired immunity and providing immunological memory
what does immunological memory enable
enables the immune system to recognise and respond rapidly to exposure to natural infection at a later date
- to prevent or modify the disease
what is the key to an effective vaccine
the ability for it to trigger proliferation of naive T cells
- success depends on whether T helper 1 and CTL responses are induced against intracellular organisms
- or T helper 2 antibody responses are induced against extracellular organisms
describe how memory cells work
- naive T cell proliferates in response to antigen
- forms effector cells and memory cells which wait for subsequent infection
- naive B cells do the same, with help from T cells form plasma cells to deal with current infection but also memory cells
- so if same antigen returns, immune system can respond quickly and potently to destroy it
what are adjuvants
compounds that enhance immunogenicity of protein antigens
- enhance the recipients immune response
- 2 broad groups: particulate vaccine delivery systems, immunostimulatory adjuvants
what are particulate vaccine delivery systems
- target antigen to APCs
- convert soluble proteins into particles, eg. alum (absorbs proteins)
what are immunostimulatory adjuvants
- directly activate APCs through specific receptors (toll like receptors)
- resulting in inflammatory responses that amplify the innate immune response
give examples of adjuvants approved for human use
- aluminium based mineral salts (alum)
- virosomes
- MF59
what are the principles of safe and effective vaccination
- either search for attenuated organisms with reduced pathogenicity to stimulate protective immunity
- or inactive organisms- will not cause lethal systemic infection in the immunosuppressed
- use purified components of whole organisms containing only key antigens or nucleic acids that stimulate protective immunity
outline the requirements for an effective vaccine
- intracellular organisms usually need CTL and Ab
- extracellular organisms usually need Abs - provides defence at point of entry
- stimulation of mucosal immunity may be required at specific mucosa - pre existing antibody may be required
- protection optimised when specific epitopes recognised
- correct epitopes must be targeted - must be safe
- must protect most vaccinees- rapid generation of herd immunity
- must generate long lived immunity- repeated booster immunisations often impractical
- cheap- will be administered to large populations
describe the effect of optimising vaccination strategies
- influences immunogenicity, efficacy and safety of a vaccine
- including number and intervals between immunisations, use of boost regimens and vaccine modulators (adjuvants) - good vaccination schedule requires a minimal number of doses and optimal interval between immunisations
- use green book for optimised strategies for NHS vaccines
what is lifelong vaccination dependent on
immune status
- pregnancy, babies, children, teens, elderly, immunosuppressed or vulnerable patients
compare the immunogenicity between the main parenteral vaccine routes of administration
- intradermal immunisation generates greater immune response than IM injection
- dermis contains more dendritic cells which facilitate the capture of antigens
- but may be difficult to administer in children - sc or IM induce similar responses
- less toxicity/anaphylaxis via IM and easier to do than sc or iD
how can issues with IM injections be overcome
- use oral or nasal route of administration
- most pathogens enter via mucosa
- adjuvants can play role in directing response to appropriate mucosa
