The immune system is immensely complex and complicated. I will not even attempt to give you a scale of the thing, but there are plenty of places you can look for more detail (video complement system, video, blog organ transplant, wikipedia). Instead I shall just take a very small part of it, the antibodies, and show you just how vast even this topic is: We will talk about immunisations, blood groups, and Henry VIII.
First off a little bit of terminology: An Antibody is a protein produced by the immune system. It helps fight pathogens by directly binding to them. Antibodies are part of the adaptive immune response, which means it is specific for a particular disease. An Antigen (Antibody generating particle) is any pattern that will cause the body to produce antibodies. This can be a glycogen on the surface of a pathogen, but can also be a surface protein on a transplanted organ, or if you are really unlucky your own nervous system (multiple sclerosis) or bones (psoriasis).
There are a lot of different antibodies. Firstly you can obviously characterise them by the antigen they bind to. This depends on the variable domains of the antibody (have a look at the image). This domain is encoded by a segment of DNA that has been generated through gene rearrangement. The many possibilities in which this can be done leads to the antibodies specificity and diversity. Secondly you can classify them by what they do, once they are bound. This depends on the constant domains of the antibody. There are five different types. Some (IgG) just act as flags for other members of the immune system (Macrophages). While others (IgM and IgA) can hold several pathogens at once and thus immobilise them in the body or even before the pathogen enters in the first place. IgD activates B-cells, while IgE triggers inflammation.
So there is no doubt about it, Antibodies are useful. A newborn baby receives a good dose of them from the mother, and continues to get them as colostrum as part of the breastmilk. Breastmilk contains two different types of antibodies IgA and IgG. The former makes breastmilk antimicrobal, and inhibits bacteria that could be taken up from the nipple. The latter is detected by a receptor in the baby digestive system and taken up to circulate in the bloodstream during the first 6 months of life. Normally any proteins taken orally would be degraded and could no longer function, but small babies can take up this special form of protection from their mother. After that, they must educate their own immune system. Each encounter with pathogens will trigger the release of antibodies, each time variable regions are shuffled and new types of antibodies are generated and remembered.
This is were vaccination comes in. An active vaccine is an antigen, which is either taken from or made to look like a pathogen. (A passive vaccine consists of antibodies extracted from elsewhere.) After inoculation with the antigen the body produces the relevant antibodies and some of the cells which produced the anitbodies then turn into memory T-cells. Memory T-cells can circulate in the body for decades or even the rest of our life and are responsible for the fast and efficient reaction of the immune system when the same pathogen comes along again. Unfortunately many pathogens mutate quickly so that our antibodies can no longer recognise them. This is why we need a new flu vaccine every year.
But antibodies are not always our friends, even when they don’t cause autoimmune diseases they make medical treatment just that tiny bit more complicated. They are behind blood groups and organ transplant rejection. The purpose of antibodies is to flag everything that does not come from the own body, whether we like it or not. My blood type is A. That means that my red blood cells display A antigens. If my body ever accidentally made a cell capable of producing A antibodies it would be eliminated in the Thymus before it ever circulated, because it knowns that the A antigen marks cells of my own body. Should I receive any blood with B antigens, my body would soon raise B antibodies and fight the invasive liquid. Actually, more likely some antibodies that can bind to the B antigen already circulate in the bloodstream and the T-cells responsible for this particular pattern will soon be stimulated to produce much more.
And this kind of problem is also behind the tragic story of Henry VIII. We all know that he went trough a series of wives because he needed ‘the heir and the spare’. But why? How come that in their 20 years of marriage Katherine of Aragon only had one living child and so many miscarriages? Anne Boleyn too, had three miscarriages after the birth of her daughter. Some we can put down to medieval practices. Fasting while pregnant to pray for a boy can not have been helpful. However a much more important factor will be the rare Kell mutation Henry carried. This causes the foetus to express unusual antigens, which are attacked by the mother’s immune system, unless she carries the mutation herself. The first time, the immune response is slow and the child may be born just in time. However the next time, having encountered this particular ‘pathogen’ before, the immune response is much faster and the foetus miscarries, or dies shortly after birth.
But there is much much more to antibodies: Immunostaining is a very important research technique, where antibodies are used to highlight proteins of interest. Antibody tests can be done to determine whether a person has had a particular disease and thus are a record of our illnesses but tests are also used to decide whether someone needs a vaccination. Assays using Antibodies (ELISA) have been tried on archaeological findings, but can also be used to test fresh water quality.
Featured Image: https://commons.wikimedia.org/wiki/File:Antibody_chains.jpg
Henry VIII: National Trust, Public domain, via Wikimedia Commons
General Information on Antibodies:
Purves Biology published by Jürgen Markl. Spektrum Akademischer Verlag 9th edition German Version.
Cellular and Molecular Immunology by Abbas, Lightman and Pober 2nd edition Saunders company
Memory T cells
Akondy, Rama S., et al. “Origin and differentiation of human memory CD8 T cells after vaccination.” Nature 552.7685 (2017): 362-367.
Whitley, C. B., & Kramer, K. (2010). A new explanation for the reproductive woes and midlife decline of Henry VIII. The Historical Journal, 53(4), 827-848.
I recommend the historical novels of Alison Weir on the lives of Henry’s wives.