3 - Vaccines Flashcards
Vaccine side effects
- 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
Autism and vaccines
Has been hypothesized that autism is induced by heavy metal poisoning associated w/ vaccination (thimerosal)
Vaccine immunology – innate immunity
- 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
Vaccine immunology – adaptive immunity
- 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
Vaccine immunology
- 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
Effector mechanisms triggered by vaccine – antibody functions
- 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
Effector mechanisms triggered by vaccine – CD8+ T cells function
- 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
Effector mechanisms triggered by vaccine – CD4+ T cells function
- 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)
Initiation of a vaccine response
- 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
Types of vaccines
- 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
Features of effective vaccines
- 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
Composition of incomplete Freund’s adjuvant
Oil-in-water emulsion
Composition of complete Freund’s adjuvant
Oil-in-water emulsion w/ dead mycobacteria
Composition of Freund’s adjuvant w/ MDP
Oil-in-water emulsion w/ mutamyl dipeptide (MDP) – a constituent of mycobacteria
Composition of alum (aluminum hydroxide)
Aluminum hydroxide gel