A Short and Simplistic Primer

To understand how vaccines work, we need to have a short and, hopefully, simplistic examination of the immune system. The medical world’s understanding of this very complex system is incomplete and continues to evolve. We will look at this amazing phenomenon in two parts.

PART ONE: Immune System Basics

What are antigens?

An antigen is essentially any substance that can invoke an immune response. Vaccines work by causing the body to make antibodies against an antigen thus protecting against the organism that bears that antigen. Typically, antigens are proteins, but they can be any component of a foreign or invading, infecting organism – or even some of our own cells. In the case of cancer cells, antigens can be the abnormal markers that appear on their surface. Antigens can also be toxins that are produced by certain organisms. In short, antigens can be anything foreign, or perceived by our immune system as being foreign to our body. When our immune system misidentifies one of our own “normal” cells as foreign, we call this an autoimmune response, which is the cause of rheumatoid arthritis, lupus, and numerous “autoimmune” diseases.

What are antibodies?

Antibodies are complex protein substances the body makes in response to an antigen. They are very specific for that specific antigen and bind to it — sort of like a key that fits a lock. Once antibodies are bound to an antigen, they form an antigen-antibody complex that enables other components of the immune system to recognize this as “foreign” and destroy it. Less commonly, antibodies are actually able to destroy the antigen or antigen-bearing organism by themselves. Antibodies can be found in almost every type of body fluid. There are also different types of antibodies characterized by where they are produced and by their structure. Besides circulating throughout the body, certain antibodies can attach themselves to other immune cells so that antigens can stick to that cell and initiate a response.

Several specialized cells are critical for the response to a vaccine or an invading agent and they all play a critical role in the success of a vaccine.

What types of white blood cells play a role in the success of a vaccine?

• B lymphocyte cells are a type of white blood cells that reside primarily in the bone marrow. Once an antigen binds to a receptor on that cell, the B lymphocyte cells undergo a change and do one of several things:
  1. They transform into a clone (specialized line) called plasma cells that produce antibodies to that antigen. Typically, these clones have a short life span.
  2. In some cases, a primed B cell (one that has been turned on by an antigen binding to it) will form a clone of plasma cells, known as long-lived plasma cells, that migrate to the bone marrow where they continue to produce antibodies for a very long time.
  3. Finally, some B cells can become “memory cells” that do not produce any antibody initially, but retain the receptor site for that specific antigen. When these memory cells are re-exposed to the antigen they were primed for, they produce antibodies and go on the defense once again.

• T cells are another type of lymphocyte that play a critical role in the immune response. They too originate in the bone marrow, but mature in the Thymus gland (where “T” comes from). Just as B cells can mature to memory cells and plasma cells. T cells can mature into 4 types of cells:
  1. Killer T cells that destroy abnormal cells or those infected by the antigen-bearing virus, bacteria, fungus or parasite.
  2. Helper T cells that basically help B cells recognize an antigen and intensify its antibody production.
  3. Suppressor T cells, that essentially close down the immune response (tell the immune system that it can now “stand down”).
  4. Memory T cells, that like Memory B cells, help to provide a rapid response to a re-exposure to the antigen they were primed to recognize.

What other types of cells are involved in the immune response?

There are also cells that initially take up a new antigen and then present it to a “naïve “or never-primed T cell. (T-cells are typically the first white blood cells to contact an antigen.) These “antigen presenting cells” consist of octopus-like dendritic cells (found in the skin, muscles and areas that have contact with the “outside world”), macrophages (a modified white blood cell that migrates into and is found in most tissues of the body) and a highly specialized subset of B cells. The most efficient antigen presenting cells are the dendritic cells, followed by macrophages and finally the highly specialized B cell subset.

What are adjuvants?

These are substances that appear to increase the immune response to an antigen and are often included in a vaccine. They act as “danger signals” that trigger a more active immune response. For decades aluminum salts were used, but over the last decade or so, newer and more effective adjuvants have been developed – many of them proprietary.

Please go to “PART TWO: How Do Vaccines Work with the Immune System?”

PART TWO: How Do Vaccines Work with the Immune System?

A vaccine causes the immune system to attack foreign substances. It contains an antigen agent formulated as 1) a live, but highly weakened agent; 2) a killed agent; 3) a portion of the agent; or 4) instructions for a human muscle cell to make parts of the agent which then trigger the same type of response as the other types of agents. Often a vaccine also contains an adjuvant as well as the desired antigen.

What happens when an antigen is introduced into the body?

First, it is taken up by either dendritic or macrophage cells which then migrate to a nearby lymph node or nodes where T cells reside. (That’s why some people who have received the COVID-19 vaccine experience soreness or swollen glands in their armpits.)

These “antigen presenting cells” bring the antigen to a T cell that has a specific receptor on its surface. Some of the T cells then transform to T Helper cells which help B cells react to the antigen so they can become antibody-producing plasma cells or B Memory cells for future use. Some of the T cells are also transformed to Killer T cells.

So, critical to the effectiveness of a vaccine is its ability to produce an initial rise in antibodies needed to prevent infection, followed by sustained low levels of antibodies. This differs from a typical immune response to an active infection which focuses more on a strong initial rise in antibodies.

How do antibody levels remain high enough to prevent future infection?

Sustained low levels of antibodies can be produced by either long-lived plasma cells that continue to produce antibodies, or by “immune memory,” which is the phenomenon of B cells mounting a very rapid and robust immune response when re-exposed to a pathogen (from which the antigen was derived). The immune system remembers and reactivates the B cells that produced the initial antibodies. Booster shots accomplish this by utilizing our “immune memory” to bolster our defenses.

How do we determine if a vaccine is working to stimulate the immune system?

A potential problem when trying to anticipate a vaccine’s likely success and protection duration is that we often look at antibody levels and try to correlate them with the anticipated degree of “protectiveness.” So much more is involved.

Since more T cells reside in the bone marrow and lymph nodes than in the bloodstream, their measurement is not so easy. Furthermore, most studies do not look at the T or B cell subsets — just their end-products, i.e., antibodies. There are other considerations regarding long-term vaccine effectiveness, such as:

• T cell response (T Helper, T Memory and T Killer cells) over B cell actions (as measured by antibody levels).
• The importance of T Killer cells, which seek out and destroy infected cells. Antibodies may play a role in preventing infection by an organism, but Killer T cells may likely play a more significant role in clearing or controlling the disease.

What about COVID-19 vaccines and other ways of achieving high antibody levels?

Injecting antibodies against the COVID-19 virus has been successful in helping to treat some people with early COVID-19 or who have recently been exposed to COVID-19. These antibodies bind to viruses, decrease their number in the bloodstream and buy time while the person’s immune system responds — including T cell activation. Unfortunately, due to the persistent mutations of the COVID virus, it is now a race to find the right antibody mixture and to manufacture and distribute it before the virus changes again!

How do we determine the success of a vaccine?

The ultimate success of a vaccine is determined by its effectiveness not efficacy.

Efficacy is a measure used in clinical trials under ideal, controlled situations. It determines how well the vaccinated group fared compared to the unvaccinated or placebo group. Unfortunately, this measurement is the first one we hear about when a vaccine has been released.

Effectiveness is an evaluation of a vaccine after real-world usage. Here, factors such as what other medications people are taking, storage, administration techniques, etc. come into play. The type of analysis used is very different than that used in a rigid clinical study – and the results may differ significantly from the clinical study-derived efficacy. However, a vaccine with an effectiveness that is lower than its efficacy may still be very successful in preventing disease or its complications.

I understand that the immune system and vaccines are very complex subjects, but I hope that this simplified presentation will help you to understand how all the different vaccines utilize the same basic pathway to work — and why they are so important and necessary.

Remember, Truesdale Health is here to help you with your medical needs! As always, you should consult your healthcare provider for any specific questions or health concerns that you may have.

Henry R. Vaillancourt MD MPH FAAFP, a Truesdale Health member and specialist in Public Health and Prevention.