Vaccination Flashcards
What is vaccination?
The induction of adaptive immunity to antigens in the vaccine
What two broad processes begin when you are first vaccinated? And what types of cells are produced?
Clonal selection and clonal expansion - proliferate and produced:
Effector cells - t helper/cytotoxic T lymphocytes etc..
Memory cells - long lived
How does immunological memory confer long lasting protection?
- Higher frequency of responder cells available - less naive
- More efficient antigen recognition/activation - may not require costimulatory signals for acivation
- Rapid migration to tissues and lymph nodes - express different homing/chemokine receptors to naive T cells
- More effective function - more cytokines produced (T cells) or antibodies (B cells)
- Longer lasting - naive cells live for days/months; memory cells persist for years and persist in the absence of the antigen - then perpetually stimulated by residual antigen
IgG and IgA importance?
IgG - humoral immunity against blood borne pathogens
IgA - humoral immunity against mucosal pathogens
How do antibodies neutralise antigens to prevent infection?
- ABs bind bacterial toxins to prevent toxins interacting with target
- ABs prevent bacteria and viruses attaching to hosts cell surface
How do antibodies opsinise antigens for uptake by phagocytes?
- Fc receptors bind to Fc region of antibody-antigen complexes
- Phagocytosis of antibody-antigen complex leads to degradation on antigen
How do antibodies activate the classical complement pathway?
- Complement mediated neutralisation -
- Complement mediated lysis - puncture holes
- Phagocytosis via complement receptors
How do CD4+ T-cells promote antibody production?
4 points
- B-cell that secretes antibody molecules have antibody molecules on their cell surface - which act as receptors for specific antigen
- Antigens are endocytose by B-cell, processed and loaded onto MHC2 molecules - and presented on cell surface to CD4+ T cells
- Specific T cells - then help with production of cytokines (CD40/CD40 ligand interactions)
- This leads to B-cell proliferation/differentiation - and so production of antibodies
What recognises danger signals that activate dendritic cell maturation?
- Signals are predominantly recognised by toll like receptors (TLRs)
- TLR4 - lipopolysaccharide (LPS) Gram- bacteria
- TLR9 - DNA with unmethylated cytidine-phosphate - guanosine (CpG) dinucleotiodes
What are adjuvants?
- Component of the vaccine preparation - that amplifies adaptive immune response
- Act directly/indirectly - to provide a signal to promote dendritic cell activation - for DCs to present antigens to naive T cells
- Many vaccines will have adjuvant properties in built - but also need to add molecules to some vaccines.
How do aluminium-based (alum) adjuvants act and what vaccines are they included in?
(4 points, 4 vaccines)
- Activates inflammasome
- Causes neutrophil infiltration and DAMP release
- Increases DC migration to lymph nodes/T-cell interactions/antigen presentation
- Alum promotes humoral immunity - but is poor at activating cell mediated immunity (Cytoxic T lymphocyte immunity)
- DTP - diphtheria - tetanus - pertussis
- Hep A and B
- Anthrax
- Rabies
What does adjuvants MF59 do?
MF59
- uses squalene
- used in influence vaccine
- Induces monocyte recruitment to injection site and DAMP release
- Increases DC cell migration to lymph nodes and increases costimulatory molecule expression
What does GSK Adjuvant system 04 (AS04) do?
- Combines with alum with monophosphoryl lipid A
- MPL - is an endotoxin like molecule - may act via TLR4 but is less toxic than LPS
- MPL increases co-stimulatory molecule expression
- Used in cervarix- human cervical cancer vaccine against papilloma virus
What is attenuation and what are live attenuated vaccines?
Attenuation - diminishes virulence of a pathogen whilst retaining antigens that can promote an immune response
Live attenuated vaccines - have inherent adjuvant properties - as are passaged through the virus in cell culture
- Results in mutations in virus genome - and triggers IgA/IgG when injected
- Generally safe - but can revert to virulent form and cause vaccine-associated paralytic (polio)
- shouldn’t be given to immunodeficient patients
What vaccines are live attenuated vaccines?
- Rabies
- BCG
- Sabin polio
How are inactivated (killed) vaccines different ?
- Unable to divide
- Pose less risk - and can be used on immunodeficient patients - cannot revert to virulent form
- Do not persist as long
- may not induce lymphocyte production to same extent
Examples of inactivated vaccines
Influenza, typhoid, hep A, Salk polio
What are Subunit vaccines and give an example?
Contain part of pathogen: proteins, inactivated toxins, non-protein antigens
- Not as immunogenic as whole pathogen
- Need multiple doses
- Need to add adjuvants
- HPV vaccine - alum adjuvant
- toxoids - tetanus toxin - from Clostridium tetani - alum adjuvant - toxin treated with formaldehyde
What are conjugate vaccines?
- T-cells don’t recognise polysaccharides - need protein
- Coupled polysaccharides onto protein to promote T-cell dependent antibody production
- targets no protein antigens
- Enables help from toxin - toxoids - specific T-cells for B-cells
Examples of conjugate vaccines
- Haemoophilius influenzae type b (Hib)
- Serogroup C neisseria meningitis
How does SARS-CoV-2 vaccine work?
- Spike protein binds to ACE-2 on epithelial cell membranes
- Vaccine produces neutralising antibodies that block ACE2 interaction
How does Pfizer vaccine work?
- BNT 162b2
- mRNA encoding S-protein in lipid nanoparticles is administered
- Cells produce protein - produces antigen for cells to target
How does BNT 162b2 RNA work?
- transcribed from a plasmid DNA template
- Lipid nanoparticles acts as carries into cells - act as adjuvants for vaccine
How does Astra-Zeneca vaccine work?
- Replication-deficient chimpanzee adenoviral vector containing the sequence for S-protein
- Based on existing vaccine for related coronavirus MERS spike protein
