Immuno + microbio - vaccines + immune BOOSTER drugs Flashcards
R0 = ?
R0 = the average no. of people one sick person will infect
To eliminate a disease with a vaccine, what are the requisites of success?
- vaccine = high immunogenicity
- Pathogen has no animal reservoir
- Pathogen must have only 1/small number of strains
- Must have no latent reservoir
Describe herd immunity
If enough people in the population are immunised, this protects unimmunised people from being infected
Describe the primary immune response to a pathogen
- Pathogen is recognised by neutrophils and macrophages by PAMPs and DAMPs
- Phagocytosis and Ag processing
- Processed Ag is presented by APCs and recognised by naive T cells –> proliferate + differentiate –> T-helper cells or Cytotoxic T cells
- T helpers activate B cells which proliferate produce IgM - antigen neutralisation OR Ab-dependent cellular cytotoxicity
- Cytotoxic t cells kill infected cells
Why is T cell memory response so gr8 compared to the primary immune response?
- T memory cells - continue to PROLIFERATE IN ABSENCE OF AG
- T memory cells express cell surface proteins to allow them to migrate to NON-LYMPHOID TISSUES
- T memory cells are EASILY ACTIVATED compared to naiive T cells
Why is B cell memory response so gr8 compared to the primary immune response?
- B memory cells = long LIFE SPAN
- B memory cells = more EASILY ACTIVATED
- High levels of PRE-FORMED IgG antibody exist –> therefore quicker response
4 features of a perfect vaccine
Easy storage
Good protection
Single injection
No adverse effects
With the influenza vaccine, how is protection acquired? Which cell controls the viral load?
Host develops an antibody which binds to viral HA and blocks viral entry into the host cell.
CD8+ T cells control the viral load
BCG vaccine - what is actually given and how is response monitored? Which cell mediates the immune response to TB?
Tuberculin injected –> observe skin reaction 48-72 hours later
T-cell mediated response
Confirmed adverse reaction to measles vaccine?
Thrombocytopenia
Confirmed adverse reaction to rubella vaccine?
Acute arthritis
+ves of a live vaccine
- Life long immunity
- Activates all phases of the immune system = good immunogenicity
-ves of a live vaccine
- Risk of reversion to virulence
- Cannot give to immunosuppressed/pregnant
- Harder to store
E.g.s of live vaccines
MMR, VZV, BCG, yellow fever
+ves of inactivated vaccines
- Can give to immunodeficient patients
- Easy storage
- No mutation/reversion
- Can eliminate wild type pathogen from community
-ves of inactivated vaccines
Requires boosters + adjuvants
Poor immunogenicity
Eg of inactivated vaccines
Pertussis, influenza, rabies
Eggs of subunit vaccines
HPV, HepB
Eg of inactivated toxoid vaccines - give two
Diphtheria
Tetanus
WTF is a DNA vaccine
- Plasmid containing a gene.
- This inserts into a muscle cell, and muscle cell expresses the viral gene –> induces immune response
WTF is a conjugate vaccine? how does it work?
Polysaccharide antigen + protein carrier
- PS antigen = produces transient B cell response
- Protein carrier = promotes T cell response, in turn enhancing the B cell response
which 2 vaccines must NOT be given to HIV +ve patients
BCG and yellow fever
Define an adjuvant
Chance the immune response without altering its specificity
- mimics PAMP activity on TLRs
Which adjuvant is most commonly used in vaccination of humans? How does it work?
Aluminium
- Bound to antigen and thus ensures a ‘slow steady stream’ of antigen.
- This helps to prime naive B cells
CpG - what is it?
It is an adjuvant - cytosine is phosphate bound to guanine
Activates TLRs on APCs
What kind of antigen is associated with better immunogenicity
Protein Ag!
polysaccharide ag have poor immunogenicity
How does vaccine schedule affect the host’s protection?
A minimum of 4 MONTHS must be had between the 1st vaccine and a booster
- this allows maturation of B cells + higher secondary response
Contraindications to live vaccines
- Immunocompromised patients
- Pregnancy
- Allergy to egg products
- Previous confirmed anaphylaxis
2 types of immunoglobulin based therapies used to boost the immune system?
Human normal IgG
Specific Ig
How is human normal immunoglobulin given? what kinda Ig is it? Indications?
IV/subcut
IgG from >1000 donors
Indicated in: post BMT, 1ary immune deficiencies, CLL, MM
3 examples of recombinant cytokines used to boost the immune response
IFNalpha
IFNbeta
IFNgamma
cytokine therapy used in Hepatitis B/C and Kaposi’s sarcoma patients?
IFN alpha
Indication for interferon beta therapy?
Relapsing MS
Indication for interferon gamma therapy? why is it useful for this?
Chronic granulomatous disease
Boosts killing ability of phagocytes
Which cells can be used to boost immune system in post-transplant patients?
T-cell replacement!
2 drugs used to block immune checkpoints –> boosts the immune system? Indication?
Ipilimumab
Pembrolizumab
indicated in advanced melanoma
MOA of ipilimumab
Blocks CTLA4 (this usually down regulates the immune response)
MOA of pembrolizumab
Blocks PD1 (usually down regulates the immune response + promotes tolerance)