Vaccination and immunological memory Flashcards
What is the primary principle of vaccinations?
Principle of vaccination is training the immune system. You are not getting rid of the disease. You are getting the immune system up to a level so that when the disease comes for real, your immune system will fight it. A vaccine is not an antibody/antibiotic but a bit of the disease which is given to you that is tricking immune system into thinking you have the infection. The purpose of vaccination is to create immunological memory.
What is immunological memory?
It is the hallmark of an adaptive immune response (tricking your B and T cells into thinking they’ve come across the antigen [protein associated with the illness]) whereby response to re-encounter with antigen is enhanced compared with response to primary encounter (first illness or vaccine) with antigen. E.g. with chicken pox, the second encounter will be better.
Memory B and T cells don’t just remember, but the next time they encounter the pathogen, the re- encounter is quicker and stronger. So, you get rid of the infection more effectively.
What are the key benefits to immunological memory?
After immunisation, you find more responder cells available (higher frequency of B & T cells)
More efficient antigen recognition/activation without need for co-stimulation. Antigen meets the T cells and T cells are activated in a much shorter amount of time (compared to first time in contact with antigen)
Cells that have taken up the antigen and activated B & T cells are much more rapid and effective at migrating to tissues and lymph nodes. They express homing chemokine receptors (not known how that works).
- E.g. if you have a memory T cell that has been sitting in your spleen for decades and the antigen comes along and activates it, it’ll go back to the source of where it was first created.
More effective function – They produce qualitatively and quantitatively more cytokines
A lot of cytokines we produce are redundant (don’t need them). But when the memory cells produce them, they’re precise and they produce exactly what and how many they need.
Longer lasting – Naive cells live for few days/months whereas memory cells persist for years
What is the antibody response to vaccination?
One main hallmark of vaccination and memory production is the antibody responses to vaccination and memory.
- The first time you come across an antigen, you find that your B cells will become activated and morph into plasma cells and they’ll produce antibodies.
- These antibodies will be of 2 classes: IgM and IgG.
- Primary antigen challenge: At 5-7 days you start producing these antibodies and you get the maximum production at 10 days to 2 weeks.
- Secondary antigen challenge: Response is predominantly IgG. The time to the peak is much quicker and incredibly efficient which can save your life.
To see if you’ve been vaccinated against a certain antigen, a test can be done to check for memory B & T cells and antibodies circling around.
How does B cell memory form?
- You have naïve cells (haven’t come across anything) which come across lymph nodes with presence of antigen (what stimulates it).
- The naïve cell then becomes activated and it morphs into a short-lived plasma cell which makes antibodies.
- For every plasma cell the immune system makes, it makes germ cells (memory cells that can live in different places e.g. bone marrow) which divide very slowly (once every decade) so you always have some saved up.
- Next time you are re-exposed to the antigen, you can skip all the steps, so the memory B cells morph straight away into plasma cells.
- The memory B cells turn into plasma cells which proliferates to make more memory.
- As children, we have such a strong immune system, particularly because we have lots of bone marrow and thymic output at that time. So, we create as much memory as possible so that in our old age, we have all this memory.
How does T cell memory form?
Three phases:
- Expansion phase where the initial activation and clonal expansion of CD8 T cells occurs. T cells then kill stuff.
- Contraction or death phase where 90–95% of the activated effector CD8 T cells die via apoptosis. Some are saved.
- Establishment and maintenance of CD8 T cell memory. Your T cell number never goes back down to zero. Some are kept to provide memory.
Two potential outcomes confront antigen-stimulated naïve T cells:
- Differentiation into effector and memory cells
- Deletion
In order for you to produce a memory cell, you need to stimulate your T cells to not only differentiate but to differentiate just the right amount. Too much activation will kill you. Not enough activation won’t work. You want just enough to make the memory.
There is convincing evidence that the outcome depends on the strength of antigenic and cytokine stimulation that T cells receive.
What is a vaccine?
- Something that modifies the immune response to the host’s benefit
- Induces long lasting immune effects (e.g. makes you resistant to an infection)
- Aims to do so with minimal side effects
- Usually made of components of a pathogen
Vaccination and Immunisation are used interchangeably
When you give a vaccine, you give an element of the pathogen itself. The body thinks it has the real thing and creates memory B and T cells which then go away and live somewhere else. Then when you have the natural infection one day, your memory B cells, T cells and antibodies from memory plasma cells are produced. Because your secondary antigen response is much bigger and quicker and the cytokines you produce are better (everything is better), you’re able to get rid of the natural infection much quicker. Symptomatically you might feel a bit run down while you’re fighting the infection, but you won’t get the illness.
Describe an ideal vaccine.
- Completely safe
- Easy to administer
- Single dose needle free
- Cheap
- Stable
- Active against all variants: hard to target something that is constantly mutating (e.g. HIV)
- Life-long protection
How did the discovery of smallpox/cow pox come about? what are the symptoms and signs associated with this disease?
In 1798 Jenner recognised that milkmaids who had contracted the mild disease cowpox were protected from smallpox infection. He demonstrated that material taken from a cowpox-infected individual could protect a previously unexposed individual from smallpox. Smallpox was eradicated in 1981.
Pasteur 1870 found that sheep inoculated with heat treated anthrax could confer protection to them. In doing so he realised that antigen exposure was necessary to prime the immune system.
One of the big problems with identifying if you have any diseases is the fact that you have a certain level of incubation period where you have no fever and you are transmittable and transferable.
Especially with smallpox, you get spiking fevers, and the development of papules, vesicles and pustules. Same is with chickenpox and other poxes. Once the fever has dropped, scabs also start to form. This is when the virus is completely gone. If you vaccinate someone you prevent all of this.
What are the key characteristics of an eradicable infectious disease?
- Safe and effective vaccine
- Generally stable target (can’t keep mutating)
- No animal reservoir (e.g. rabies. If everyone is vaccinated and then something comes back from the animal reservoir, you have to start again. So, this is a big problem)
- Eliminates persistent infection, or more commonly get rid of infection within host so persistently infected host can’t transmit
- Easy and reliable diagnostics (if someone is sick we can see straight away)
What were Pasteurs main principles of vaccination?
- Isolate
- Inactivate
- Inject
What are toxoids?
- toxoids produced from the pathogen that stimulate an immune response that can also be recognised by PAMPs.
- They have certain pattern which is recognised by T cells, dendritic cells etc.
(e.g. Diphtheria and Tetanus toxin)
What are Capsular Polysaccharide?
Capsular Polysaccharides (eg: Streptococcus pneumoniae, Neisseria-Streptococcus Neisseria meningitidis, Hemophilus influenzae-meningitidis, influenzae)
- Sugars on top of bacteria which are recognised.
What are Surface Antigens?
Surface Antigen: recombinant protein (e.g. Hepatitis B 8)
- You use the proteins from that virus which tricks the immune system which creates immune response. You don’t actually have the virus so don’t get sick but you create memory against that antigen.
What is an adjuvants?
An agent that may stimulate the immune system and increase the response to a vaccine
