By Colin Michie
Every moment of every day, we fight off microscopic invaders. As you read, antibodies are clearing viruses and bacteria from your bloodstream, your eyes, your nail beds – and they remember all your foes, new and old!
These events happen at a microscopic level. In this world of tiny invaders, identifying bugs needs accurate and rapid molecular contacts. Frontline immune defences use antibodies or immunoglobulins. These Y-shaped proteins have extremely specific sensors on their tips that touch and massage all surfaces around them. If they bind, Velcro-like to a foreign virus, bacterium, toxin or inflammatory molecule, they neutralise the risk. Using their tail portions, they can signal to immune cells such as neutrophils to have the target eaten and destroyed. This process takes just a few minutes. If antibodies are used, a feedback system ensures a second wave of reinforcements with similar molecules is made by our B cells – an immunological memory that repeatedly hones its weapons and soldiers throughout life.
Immunoglobulins are common proteins – there are many millions of these molecules in each millilitre of blood. They move from the circulation into lymph, tears or mucus too, continually checking to reinforce our protective barriers. The B cells in immune systems make immunoglobulins in blood, lymph nodes, the spleen and bone marrow, even before our birth. During pregnancy, the placenta pumps mother’s antibodies into the foetus to protect it too; when breastfeeding a similar process deploys her specific antibodies to her milk to protect her infant.
Those B cells each produce only one type of immunoglobulin with a highly specific set of sensors – a monoclonal antibody. Monoclonal antibodies can be manufactured using cells grown in vats. Since 1986, they have safely treated patients for infections, sepsis, transplantation, multiple sclerosis, cancers. They can have drugs or tracers attached to their tail portions to carry these to a target in a test tube or a patient. Several recent monoclonals have been designed to regulate the B cells that make them. As mixtures, antibodies can support individuals with immunodeficiencies. For instance, children born without the ability to make all their own antibodies require regular transfusions of immunoglobulins. They are usually treated with products prepared from blood donors to ensure a wide variety of antibodies is provided.
In some, antibodies can cause illness. Immunoglobulin Es, for instance, are directed particularly to eliminate parasites from gut, lung and skin. However, in developed societies where parasites are uncommon, IgE drives the increasing burden of allergies. The tail portion of these antibodies engages with cells that release histamine. IgE is associated with anaphylaxis, asthma, rhinitis, conjunctivitis and food allergies. Allergy tests show what allergen engages with IgE and therefore what to avoid. Pollen to peanuts, dust mites to mould spores: measures need to be taken to reduce the risks and consequences of allergies. Rarely, antibodies can attack our own tissues in error. These auto-immune illnesses include vitiligo, thyroid disease, systemic lupus erythematosus, rheumatoid arthritis. As with allergies, medical treatments are required; novel strategies to control B cells are being tested.
It stands to reason that to improve our health as individuals and communities, it is advantageous to develop a rich variety of antibodies. Broader repertoires deliver improved pattern recognition, direct more effective surveillance, neutralising and limiting the spread of any new mutations. An individual with antibodies to polio is not likely to spread this disease because the polio virus cannot infect others. This idea has directed vaccination programs. Vaccines provide a stimulus that copies an invading pathogen so immune cells generate protective antibodies. Vaccination of small island populations, such as that on St. Maarten, can limit the spread of infections, whether it is measles, Covid-19, tetanus, cervical cancer or influenza. To prepare for the next pandemic, an ideal vaccination system should maximise access for all age groups in all populations.
Their great sensitivity and specificity drives monoclonal antibodies, or parts of them, to a legion of uses. Whether in a pregnancy test kit, a diagnostic or research laboratory or a point-of care check for disaster medical kits, they are invaluable. Monoclonal antibodies have been harnessed to purify medications including insulin or growth hormone, or to ensure foods are not contaminated by toxins or pathogens.
We each have our own particular mixture of antibodies, just like our fingerprints, voices or gaits. This encyclopaedic protein soup records immune responses to our infants if we are women, the colds they have shared with us, the homes in which we have lived, our occupations, illnesses, vaccines, perhaps even the bugs that have bitten us. It keeps out invaders and stops malignancies developing. If our antibodies stop an infection in us, they can arrest its spread in our communities. Our molecular ubuntu is an amazing gift.
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