As I mentioned in a previous blog entry, antibodies are a vital tool used by biomedical researchers every day. This is one of the reasons I’m interested in them, but antibodies also play a critical role in our immune defence against invading pathogens such as viruses and bacteria. In addition, they are increasingly used in medical treatments. I’m going to try to briefly describe what they are, what they do and how we use them.
Antibodies – the basics
Antibodies are core parts of our immune system and have evolved to combat infectious disease. To properly describe what they are and what they do, I’ll refer to the diagram below. I’m not going to describe how each of us can generate approximately one hundred million (!!) different antibodies, but there is good coverage of this on Wikipedia (see the section on Immunoglobulin diversity).
Antibodies are made by our immune cells and are proteins that contain a heavy and light chain. The heavy and light chains in an antibody together create an ‘antigen-binding region’ that recognizes a very specific target molecule.
What substances are recognised by antibodies? In theory, practically any chemical structure can be recognised by an antibody. However, there is an important distinction between the ability to be bound by an antibody and whether or not this leads to an immune response. Some antigens do not, by themselves, cause antibody production; antigens that promote antibody production are called immunogens.
Many substances (such as sugars) are recognised by antibodies, but only proteins can generate a full immune response because they can be detected by the two types of immune cells (B cells and T cells) that are required to generate antibodies. As well as containing protein, there are other basic requirements for an antigen to be an immunogen:
Foreignness (to prevent us from attacking our own cells)
Size (larger molecules are often more immunogenic)
Chemical complexity (things that contain different chemical groups and structures)
However, there are a number of exceptions to these rules and we are still learning about the generation of immune responses to antigens, which is an important area in vaccine development.
The role of antibodies in immune defence
During infection, antibodies can help to fight infection in three main ways. An antibody binding to the surface of a pathogen can lead to:
1. Neutralisation or disarmament of the pathogen
2. Phagocytosis (eating) of the pathogen by our immune cells
3. Complement activation – a pathway that leads to the killing of pathogens
An effective antibody response helps clear infections from our body and is essential in our response to pathogens such as influenza viruses. However, it is extremely important that we generate appropriate antibody responses, as I discuss in the blog entry ‘Are we too clean?’. Allergies are caused by the stimulation of an immune response (including antibody production) by harmless environmental components such as pollen.
In autoimmune diseases such as Systemic Lupus Erythematosus (SLE), the body generates self-antibodies – that is, antibodies that recognize our own cells and target them for destruction. Antibodies are only helpful when they are produced in response to appropriate stimuli.
Antibodies in research
Our ability to make new discoveries about the tiny world of cells is absolutely dependent on the development of techniques and technologies to manipulate these cells. Antibodies are one of the most important tools in any almost any cell biology or infection lab. I use antibodies in many of my experiments to visualise parts of the cell, quantify the amounts of protein both inside and outside cells, or to block interactions between cells. Many companies exist solely to generate new specific antibodies, and we use these to help understand the role of individual proteins in our cells.
César Milstein discovered the principle that allows scientists to produce specific monoclonal antibodies, and along with other immunologists, he was awarded the Nobel Prize in Physiology and Medicine in 1984 (link here to read more about it).
Antibodies in medical treatments
Monoclonal antibodies account for a third of all new therapies in production. These include treatments for breast cancer, leukaemia, asthma, arthritis, psoriasis and transplant rejection. There are also a number of antibodies in late-stage clinical trials that may lead to future treatments.
Monoclonal antibodies are used in cancer treatments and can have a number of beneficial effects; they allow the immune system to recognise cancer cells as enemies and target them for destruction; they can block growth signals to cancer cells and prevent new blood supply and thereby slow cancer growth; they can be used to deliver radiation directly to the cancer cells and reduce damage to normal tissues.
The technique for creating specific monoclonal antibodies came from a small lab by scientists making basic investigations into the world around them (1). It has had an enormous impact on biological science and medicine, but this was not predictable. The funding of basic (as opposed to more applied) research is under threat in the current cash-strapped climate, but funders should note that the best research should be prioritised for support, as it’s not easy to predict what will be the most useful.
- Kohler & Milstein (1975). Continuous cultures of fused cells secreting antibody of predefined specificity. Nature, 256, 495