Antibodies and Immune system

Question

I was just educated by my physician about some details of the differences between the qualitative and the semi-quantitative COVID-19 antibody tests. I understand now that the result of the semi-quantitative test is not an accurate indicator of the level of immunity that you may (or may not) have, and therefore should not be used by those who have had the disease as a determinant to decide whether or not to get vaccinated.

(As a side note, for someone who has had COVID-19 already, this means that the Qualitative anti-body test is completely pointless. All is does is tell you what you already know - that you have had COVID-19)

My physician explained to me that the antibodies in your blood (whether they are from a prior infection or induced by the vaccine), are not what actually fights the virus. It is the white blood cells that fight the infection by attacking the virus. He explained that the white blood cells are what actually produce the various types of antibodies, and that the "antibodies attach to the viruses and make them attractive targets for the white blood cells."

My question is this: Obviously, if the white blood cells are what fights the virus infection, and they are modified/tuned/adjusted in some way to recognize or react more to a specific pathogen, why don't we produce a test that measures the amount of white blood cells that have been so tuned to the COVID-19 viral signature? Is this because the white blood cells are not adjusted in any way, that the antibodies which are chemically "tuned" to recognize the COVID-19 viral signature, and which attach themselves to invading COVID-19 viruses, are what the white blood cells are attracted to ?

But if that is the case, then why is the level (in the blood), of these specific COVID-19 antibodies not a reliable indicator of the ability of the immune system to fight COVID-19 infection?

Answer 1

First a disclaimer: I am not an immunologist by any stretch of the imagination, but I do work on SARS-CoV-2, the virus that causes COVID-19 (the syndrome/disease).

The tests in general are measuring the presence of antibodies in your blood, not the white blood cells themselves. The white blood cells aren't what starts off the process, but getting them involved once a person has antibodies means that much more antibodies are produced and (generally) results in a shorter, less serious infection or no infection at all. The aim of the vaccine is to pretend to be an infection and result in a response from the immune system that will be protective when a real infection comes along.

Immunology is a huge and very very complex field of study in its own right. A short summary of what happens is that the body recognizes an infection, and takes part(s) of the infecting organism and presents those on the cell surface, where they are recognized by a type of white blood cell, which then takes these and generates antibodies against them. The antibodies bind to their targets and cause a second type of white blood cell to engulf the antibody+target. This whole system is known as the adaptive immune system, as it is shaped against infections that the body has seen before. There is also the innate immune system, which is the first line of defense for the body, but doesn't have much to do with antibodies

Anyway, on to your question:

why is the level (in the blood), of these specific COVID-19 antibodies not a reliable indicator of the ability of the immune system to fight COVID-19 infection?

The answer is that the body produces neutralizing antibodies. Some people produce lots, some people produce very little, but (and it's a big one), if they are producing neutralizing antibodies, then they will be neutralizing the infecting particles. They systems we use to detect the antibodies are (relatively) crude and only capable of detecting levels that are sufficient to neutralize almost any incoming infection. I'm not sure on the exact levels, but it will be something like micrograms of antibody per ml of blood.

To give you some idea of just how many actual antibody molecules this is per ml:

The molecular mass of IgG (the major type of antibody, makes up about 75% of blood serum protein) is about 150,000 grams per mol (a mol is 6 x 10²³ molecules (AKA Avogadro constant)). A microgram is 1/1,000,000 th of a gram. Using basic chemistry calculations:

number of mol = mass/molar mass
              = 0.000001 grams/150,000 grams per mol
              = 6.67 x10^-12 mol

number of molecules = number of mol * Avogadro constant
                    = 6.67 x10^-12 * 6 x10^23
                    = 4 x10^12

That's a whopping thousand billion molecules per ml. If it were nanograms/ml (that's a 1000th of a microgram) it would still be in the billions of molecules/ml, and so-on down the scale.

Now, of course, those antibodies are spread out via the blood to all parts of the body, including sites like the lungs and gut. A viral infection from SARS-CoV-2 is probably less than 1000 particles, so even at the lower end of the scale you are still going to have quite a lot of antibody present relative to the amount of virus.