L15 - Vaccination Flashcards
What are the 3 occasions that we receive vaccines?
Childhood vaccination
Travel vaccines
Vaccines for the elderly
What was the hysteria surrounding the MMR vaccine?
linked MMR vaccine to autism - NOT TRUE
What cells mediate adaptive immunity?
Lymphocytes
What cells are required for the initiation of an adaptive immune response?
Dendritic cells
How does immunological memory confer longer lasting protection?
more responder cells available
more efficient antigen recognition
Rapid migration to tissues and lymph nodes
More effecting function
Longer lasting
What antiboides are important for humoral immunity against BLOOD BLORNE pathogens?
IgG
What antibodies are important for humoral immunity against MUCOSAL pathogens
IgA
What do immunoglobulins do?
neutralise antigens - block interaction with target
- bind bacterial toxins
- prevent viruses attaching to surface of host cell
- prevent bacteria attaching to surface of host cell
How do immuoglobulins opsinise antigens for uptake by phagocytes?
Fc receptors bind to Fc region of immunoglobulin - antigen complexes
antigen complex -> degradation of antigen
How do immunoglobulins activate the classical complement pathway?
complement mediated neutralisation
complement mediated lysis
Phagocytosis via complement receptors
How do CD4 T cells promote antibody production?
Help interactions - CD40/CD40ligand
leads to B cell proliferation & differentiation
Why are CTLs (CD8) important for INTRACELLULAR pathogens?
recognises virus infected cells by peptides displayed on MHC
Why is it useful to have a vaccine that activates CD8 and CD4?
catch virus extracellularly and intracellularly
What is dendritic cell maturation activated by?
danger signals
what are DIRECT danger signals recognised by?
TLRs 4 and 9
What are indirect signals?
secretion triggered by pathogens
What molecules are secreted by macrophages in response to microbial molecules?
TNF-a
IL-1b
What are adjuvants?
component of vaccine preparation that amplifies adaptive immune response
How do adjuvants act?
directly or indirectly to provide signal to promote dendritic cell activation
What are alum-based adjuvants?
precipitate of aluminium hydroxyphosphate
How do alum-based adjuvants act?
activate inflammasome - IFNb
cause neutrophil infiltration & DAMP release
What do alum-based adjuvants increase?
DC migration to lymph nodes
T cell interactions
antigen presentation
What immunity is alum poor at promoting?
CTL immunity
GOOD AT HUMORAL IMMUNITY
Other adjuvants in clinical use?
MF59 - oil-in-water, squalene
GSK Adjuvant System 04 (AS04)
What is the MF59 adjuvant?
induces monocyte recruitment to injection site
increases DC migration to lymph node
What is the AS04 adjuvant?
combines alum with monophosphoryl lipid A (MPL)
MPL = endotoxin - less toxic than LPS - still act via TLR4
increase co-stimulatory molecule expression
What are live attenuated vaccines?
retain antigens
introduce mutation in cell culture to reduce virulence
often have inherent adjuvant properties
Cons of live attenuated vaccines?
can revert to virulent form
don’t give to immunodeficient subjects
Examples of diseases treated by live attenuated vaccines?
Rabies
BCG
Sabin Polio vaccine
What is the Sabin Oral Polio vaccine?
3 attenuated strains
mutate by passaging through monkey kidney epithelial cells
transiently infect - vaccine colonise intestine - stimulates IgA production
What reduces virulence in the Sabin Oral Polio vaccine?
nucleotide changes
What are inactivated (killed) vaccines?
unable to divide
pose less risk that live attenuated
cannot revert to virulent strain - better if immunodeficient
Cons of inactivated vaccines?
do not persist as long as live vaccine
may not induce lymphocyte production to same extent
Examples of inactivated vaccine?
influenza
typhoid
hepatitis A
Salk Polio vaccine
What is the Salk polio vaccine?
3 diff. polio strains
inactivated by formaldehyde
administered by intramuscular injection = less mucosal immunity than Sabin
What are subunit vaccines?
contain A PART OF THE PATHOGEN:
- associated proteins
- inactivated toxins (toxoids)
- non-protein antigens
How can subunit vaccines be made more immunogenic?
multiple doses to extend period of stimulation
use adjuvants
What does the HPV vaccine contain?
L1 capsid proteins - VLPs
Alum adjuvant
non-infectious as no nucleic acid
What are toxoids?
toxin treated with formaldehyde to produce inactive toxoid - cannot cause disease
needs adjuvants to stimulate immunity - alone is not sufficient to give a signal to activate DCs
What are conjugate vaccines?
capsular polysaccharides conjugated to proteins e.g. toxoids
help from toxin specific T + B cells specific for capsular polysaccharides
Examples of conjugate vaccine?
Haemophilus influenzae type B
serogroup C N. Meningitis
SARS-CoV-2 vaccine?
SPIKE PROTEIN
Pfizer - BNT162b2
mRNA encoding S-protein lipid nanoparticles
- BNT162b2
Astra-Zeneca - adenoviral vector- does not replicate but expressers S-protein
