7. Vaccination Flashcards
Preliminary observations of vaccine-induced prothrombic immune thrombocytopenia (VIPIT)
- AstraZeneca COVID-19 vaccine appears to be associated with rare cases of serious blood clots and thrombocytopenia
- Patients with presumptive and confirmed VIPIT should be treated similarly to HIT; anticoagulants safe to use in HIT likely safe to use in VIPIT
Potential insights into VIPIT through mechanisms driving autoimmune herapin-induced thrombocytopenia (HIT)
- Formation of anti-PF4 antibodies; PF4 is a molecule produced by platelets
- Immune complexes (antibody-antigen) are created
- Complexes have a lot of FC portions exposed and PLATELETS, neutrophils, monocytes, macrophages have FC receptors that bind
- Positive feedback for more PF4 release = more complexes = runaway train promoting inflammation
- Endothelial cell activation = area gets stickier = recruitment of more leukocytes
What is the prevention of illness through the transfer of pre-formed antibodies (eg. IgG)?
Immunoprophylaxis
- While protection is immediate, it is TEMPORARY and can only be offered if the exposure is recognized
- Protection is also time-sensitive. Post-exposure immunoprophylaxis must be initiated within a short time frame, usually within days of exposure to the infection
- NOTE: this is distinct from passive immunity conveyed from mother to progeny
Natural exposure
Unprotected encounter with pathogen
Inoculation
The practice of introducing an infectious agent or infective material into the body in the hopes of inducing protection against the infectious agent. In other words, plopping a live full-strength pathogen into a body in a controlled manner
Variolation
Specifically refers to inoculation with smallpox matter, because variola is the name of the virus that causes smallpox
- aka this is an inoculation procedure specific to smallpox
Vaccination
Weakened version of a pathogen is introduced into the body to prepare the immune system for a potential encounter with the full-blown version of that pathogen (or a closely related one)
Rate the safety level from least safe to safest:
1. Variolation
2. Natural exposure
3. Vaccination
4. Inoculation
2, 4, 1, 3
What are 3 factors required for a successful vaccination?
- Must be ANTIGENIC
- An antigen is a molecule recognized by the immune system; if the vaccine is not recognized by the immune system it is useless
- The ability of an antigen to induce an immune response - Must be IMMUNOGENIC
- Able to induce an adaptive immune response (cell and/or humoral)
- Many antigens recognized by lymphocytes fail to elicit immune responses in the absence of adjuvants
- Requires activation of innate immune responses which induce the production of cytokines and activation of dendritic cells, which are required to launch an effective adaptive response - Effectiveness: Must evoke protective levels of immunity
- At the appropriate site
- Of relevant nature (Ab, Tc, Th1, Th2)
- Of adequate duration
Vaccination strategies
- Live attenuated organism
- low safety, high efficacy
- cannot be given to everyone; ex. young, elderly, immunocompromised
- mimic infection but bc of proliferation this virus can also spread - Killed organism
- still has all the parts = polyclonal response
- multiple different antibodies produced = body of antibodies that can bind the antigen if it shows up - Protective subunit antigen
- high safety, low efficacy
- might produce a monoclonal response if level of affinity of b cell receptors are lower for all sites except for the 1 it binds
- most responses are polyclonal even with a subunit vaccine
Mechanism of mRNA vaccine
Trying to get your own cells to produce proteins recognized by antibodies
What can route of administration directly impact?
The level of antibodies
What if you want a specific memory response? Humoral versus cell-mediated
Adjuvants provide selective induction of humoral or cell-mediated adaptive responses
- Humoral responses most effective against extracellular pathogens
- Alum (aluminum sulfate) favours humoral antibody responses (Th2)
- Cell mediated responses most effective against intracellular pathogens
- Freund’s complete adjuvant (killed mycobacteria) favors cell mediated responses (Th1)
What are 3 things that adjuvants can do?
- Provide selective induction of humoral or cell-mediated adaptive responses
- Activate acute local inflammatory responses and key players like antigen presenting cells
- Maintain high local concentration of antigens
- do not want rapid diffusion of antigens
Why are ‘boosters’ given?
- For most vaccines, the immunity against a partial pathogen has a tendency to wear off over time
- In this case, a periodic booster administration is given to strengthen and lengthen the duration of immune protection
