Adaptive Immune Defenses

By July 22, 2020 Commentary

I have realized from reader questions that I have not done a good job of explaining the context for antibody and T cell research summaries that I put up.  This is a very complex area, so I will try briefly again here to create a context, so that there is some better understanding of why I think certain studies are important.  This is a highly simplified description.  And for those who want more background, I encourage you to go to sites like this (Immunopedia) or others that you can find on the internet.  The basic structure of our immune system has two main components.  One, the innate immune system, deals with infections and other external threats as they occur.  The second is designed to provide a long-lasting defense against the same threat recurring, and is referred to as the adaptive immune system.  In the case of a pathogen, like the current strain of coronavirus, the adaptive immune system has two primary components to aid in protecting against re-infection.  One is built on what are referred to as B cells, which are responsible for creating antibodies.  Antibodies are small molecules which have the capacity to bind to certain recognized areas on other larger molecules.  The second is built on T cells, which both can help B cells be alerted to a threat and respond to it, and can themselves directly engage the threat.  There are many, many sub-populations and types of B cells and T cells, which have different roles and capabilities.

A major aspect of the adaptive immune system is the ability to remember and recognize prior threats.  An infectious agent, like any organic entity, is made up of a variety of proteins–large molecules.  These protein molecules have a defined sequence of amino acids of which they are made up.  Upon infection, our bodies identify various parts of these proteins, and “remember” them–they develop B cells and T cells that can recognize the same sequence if it is encountered again.  The B cells create antibodies which can specifically recognize and bind to these protein fragments.  If the protein or part of a protein recognized or bound to is the part of a virus that is used to gain access to human cells, or to replicate once inside the cell, the antibodies that bind to that protein will block the ability to gain such access or to replicate, and are referred to as neutralizing antibodies.  The T cells that recognize the sequence can either signal B cells that antibodies are needed or they may directly engage the virus to disable it and/or they may call other components of the immune system to help disable the virus.  In regard to a specific virus, B cells and T cells will typically develop the ability to recognize multiple parts of the virus.  This multiplicity of memory is important, because viruses tend to frequently change their sequences, and the more parts that can be recognized, the less likely that a mutation allows complete evasion of the immune system.

So a good adaptive immune response to any agent should be found among both B and T cells, it should be able to recognize multiple parts of the virus, and it should last over a number of years.  So that is what many researchers are searching for.  And what I see as important are studies that report on the B cell and antibody memory development, but also the T cell memory development, how strong that appears to be and how lasting.  I also look at papers on testing methods, because it is apparent now that some tests aren’t looking for the right kind of antibodies or have too high a threshhold for positivity.  And because coronaviruses have been around and infecting us all for decades, there was always the possibility that the antibodies and T cells resulting from prior coronavirus strain infections would help fend off this strain.  So I have been very excited by the research showing that such prior immune defenses do exist and do work against this strain.  That is the most likely explanation for such a wide variation in susceptibility to infection and seriousness of illness.

The research so far pretty clearly shows that:

  1. T cells may be more important than B cells and antibodies in protecting against infection by coronaviruses.
  2. Strong antibody memory is created, and the memory is created against multiple virus protein fragments, is probably stronger in people with more severe disease, and that memory includes neutralizing antibodies.
  3. Strong T cell memory is created, again directed against multiple protein fragments.
  4. A significant portion of the population has cross-reactive antibodies or T cells, meaning that antibodies and T cells resulting from infections by other coronavirus strains work to defend against this one.

One consequence of these characteristics is that we are seeing almost all infections be asymptomatic or mild, and many people simply aren’t getting “infected”.  And population immunity, or a dramatic slowing of transmission, is likely to occur at much lower levels than are commonly predicted.  All good news, not that you will get that perspective from the traditional media.

 

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