Immune Memory

Why do we need immune memory?

When T cells and B cells are created, there have to be millions of versions to account for every possible antigen that they might encounter. There is simply not enough space in the blood to create the thousands of each copy of antibody and T cell that would be needed to fight off that pathogen on the first encounter. Therefore, when encountering an antigen for the first time, the body only has a few B and T cells that match that antigen. Therefore, there is a delay as it takes time to find the relevant B and T cells, multiply them to make the required number and activate the specific immune response.

Once the body has met the antigen once, it knows that this pattern of antibody and T cell receptor is useful, and that it may encounter that antigen again in the future. Therefore, it is really helpful to have large number of the relevant B and T cells hand around so that next time the pathogen with that antigen is encountered, a rapid and substantial response can be launched to destroy that pathogen before it causes too much damage.

 

Memory B Cells

  • When B cells are activated they become plasma cells or memory B cells.
  • Both have undergone affinity maturation (to become more specific to that antigen) and antibody class switch (to create a single type of antibody).
  • Plasma cells produce lots of antibodies to fight the acute infection, but once the infection is cleared they gradually disappear.
  • Memory B cells don’t contribute to the acute infection, but hand around waiting for a subsequent infection with the same pathogen.
  • Once the antigen is encountered again, memory B cells proliferate and differentiate into plasma cells and start producing antibodies.
  • On subsequent responses to infection, the IgG response is much faster and larger.
  • IgG is more readily produced by memory B cells, and measuring specific IgG is the most useful marker of immunity.

 

Memory T Cells

The first time antigen is encountered, CD4 and CD8 cells with specific TcRs rapidly proliferate and differentiate.

Most of these disappear after the acute infection.

However, a large amount of specific CD4 and CD8 cells stick around as memory T cells and await subsequent infections, where they can proliferate and differentiate faster and provide a more rapid specific immune response.

It is very difficult to measure the immunity of CD4 and CD8 cells, and we do not attempt to measure this in clinical practice (relying on the IgG response as a marker of overall immunity).

 

Vaccination (you can see the full vaccination schedule here)

The purpose of vaccines are to provide stimulation by antigens specific to a pathogen that the person may encounter in the future without giving them the full infection. This gives them a head start in clearing the infection if they encounter that pathogen in the future.

Each subsequent immune response to an antigen, gives a greater immune memory to the pathogen. Additionally, the immune memory tends to fade over time. This is why we repeat vaccines several times during the vaccination schedule.

There are several ways in which vaccines can present the immune system with antigens specific to that bacteria:

Subunit vaccines only contain specific parts of the organism (such as the exact antigen required) to stimulate an immune response and the subsequent immunity to the disease. They cannot cause an infection and are safe for patients with immunosuppression (although they may not have an adequate response).

Inactivated vaccines contain pathogens that have been treated to kill them (e.g. with heat) to make them unable to cause an infection but still contain all the necessary antigens to stimulate an immune response. These are also safe for patients with immunosuppression (although they may not have an adequate response).

Live attenuated vaccines contain a weakened version of the virus, and are still capable of causing the infection and should be avoided in immunosuppressed patients. The following vaccines are live:

  • Measles, mumps and rubella vaccine (all three contain weakened viruses)
  • BCG (contains a weakened version of tuberculosis)
  • Shingles (contained a weakened varicella-zoster virus)
  • Nasal influenza vaccine (not the injection)

 

Herd Immunity

This is where enough of the population has become immune that the pathogen is unable to survive in hosts and be passed between members of the population. The pathogen therefore cannot exist long enough in large enough numbers to infect people that aren’t immune. Therefore, people that aren’t immune are protected because the population (the herd) as a whole is protected.

An example of how this works in practice is the MMR vaccine. When everyone was receiving the MMR vaccine, infection with pathogens like mumps was very rare even though there were small numbers of people who refused the vaccine (they were protected by the herd immunity). When the MMR scare happened and people started refusing the vaccine, the pathogens were able to re-establish themselves in the herd, and the diseases started make a comeback.

An example of a success story of vaccines is smallpox. This used to be a huge global problem, causing significant morbidity and mortality. After an extensive global vaccination program, herd immunity was developed and the smallpox had no hosts to survive in. The virus died out and now no longer exists, so we no longer have to vaccinate children to smallpox because our previous herd immunity wiped it out.

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