Immunity is a complex topic. This article overviews the basic concepts and vocabulary to give you a foundation before you start looking at the details. When you are studying, break this topic up into chunks so that you’re not overwhelmed by the amount of information.

Also: expect to find this topic confusing! Feeling confused is part of learning and shouldn’t be thought of as a bad thing, or some sort of failure. It’s just a step toward understanding. If you’re not confused, that’s more worrying because it means you’ve probably made incorrect assumptions.

What is Immunity

Our bodies are wet and warm, and full of useful molecules. This makes them an attractive environment for bacteria, fungi, viruses and other organisms to live. Our bodies host many such organisms that benefit us, some of which are absolutely required for normal functioning (eg the bacteria that break down food in our gut).

But there are other organisms that would like to live and reproduce in and on our bodies that can harm us by their presence. These are disease-causing organisms, and they are called pathogens. Remember these are tiny things without brains and they have no concept of our bodies as an entire organism. They just want to grow and reproduce, with no mind to consider they are damaging their environment.

Immunity is the body’s ability to identify and defend itself against pathogens.

What Defenses do we have?

The first line of defense is to stop invaders gaining entry to our bodies. For example, our skin protects us by making it harder for pathogens to get into our tissue fluids (wounds are more likely to become infected than unbroken skin). Another example: incoming food is passed through the highly acided stomach environment, which kills many organisms before they reach the intestines. But these defenses don’t count as part of the immune response.

If a pathogen does get into our bodies (especially into our blood, intracellular fluid, or cells), then the body - we hope! - will spot, kill, and remove the pathogen. This is the immune response.

The body has cells that are specialised for detroying and removing pathogens. However, it would be pretty difficult for any one cell to be able to accurately recognise every possible different threat, especially as pathogens are constantly evolving to try to get past our defenses. This is why the body uses antibodies.

What is an Antibody?

Antibodies are small protein molecules that are carried around by the blood and tissue fluids. They act like little sticky labels - they stick to anything weird/suspicious and label it as being “not part of my body”.

Antibodies aren’t huge; they only bind to one part of the pathogen, rather than grabbing the entire thing. Usually they bind to a large protein on the surface of the pathogen. The antibody’s physical presence might interfere with the functioning of the pathogen, but more importantly the antibody labels it up to other parts of our immune system as being something that needs to be removed.

But remember: it’s not possible to make one molecule that binds to everything suspicious. For this reason, there are many different antibodies in your body. These vary in a small part of the structure at the end of their arms. Depending on any one antibody’s particular structure, it will be able to bind to different things.

(Recap: do you remember how protein enzymes have a binding site that is very specific to their substrate? Antibodies, which are also proteins, have 3D structures that allow them to be similarly specific in their binding.)

What is an Antigen?

Antibodies with different tertiary structures are able to bind different antigens

Any molecule that an antibody binds to is called an antigen. It’s called that because it generates an immune response.

It’s important to understand that an antigen isn’t a particular type of molecule. Antigens can be viral coat proteins, polysaccharides, lipids, or … just about anything really. If an antibody binds to it, it’s called an antigen - that’s it.

Anything a child plays with is called a “toy”
Anything more than 100 years old is called an “antique”
Anything that gets bound by antibodies is called an “antigen”

Not every part of a pathogen will act as an antigen. But you hope that at least some parts of it will, otherwise your body won’t know it’s there. Luckily, pathogens tend to come covered in loads of interesting proteins which very often do serve as antigens.

If the pathogen does carry an antigen, and if that antigen gets bound by an antibody (labelling it as “not part of my body”), then the immune system will destroy it and remove it from the body.

Where do Antibodies come from?

During an infection, antibodies are released by B-lymphocytes (a type of white blood cell). These cells have the ability to produce and release antibodies in huge numbers. They synthesise the antibodies using a normal protein synthesis process.

But … B-lymphocytes are not all the same. Remember how the immune system uses many different antibodies, with slightly different structures in that variable section? Each individual B-lymphocyte cell can only make ONE type of antibody, with one particular structure. So there are different B-lympocytes for every different antibody made in the body. Which is amazing as that means there are a LOT of different B-lymphocytes.

This is all possible because the B-lymphocytes have slightly different DNA coding just for that variable section of the antibody. This is more than a bit mindblowing because it means that B-lymphocytes are not genetically identical to each other!!! Exactly how this happens is complicated so I’m not going to get into that right now. But the fact they’re all different, and make different antibodies, is crucial to the whole way immunity works.

(There are also T-lymphocytes, which have many similarities to B-lymphocytes but play a different role. We’ll get to them later. )

How do we get the right Antibodies for our needs?

There are vast numbers of different bacteria and fungi and viruses that might harm us, and they are constantly evolving. So we need a immune system that can react to unexpected threats. Something that can recognise anything strange, rather than just a check-list of well-known pathogens.

Important: we DO NOT respond to new pathogens by creating new antibody variations specially designed to bind to them!

This crucial fact is often missed by students.

At first this might seem unintuitive, especially as many news reports suggest otherwise. But think about it. How could we? How would the body even know something was a pathogen if an existing antibody hadn’t already labelled it as such? And even if it did magically know it was a pathogen, how could a lymphocyte know what DNA sequence it would need to be able to synthesise a protein sequence that folded to a structure that was able to bind to it?! And then create that sequence??!

This leads to another mindblowing fact: we ALREADY have B-lymphoctyes that can make antibodies for pathogens we have never encountered. Including for pathogens that haven’t even evolved yet.

Antibodies are not designed to fit specific antigens.

Instead, we create a huge random jumble of antibody variations with a huge variation of different binding sites. Some might be useless, and many will never be required, but there are so many that there’s a really good chance at least one of their binding sites will just happen to be a good fit to some part of a new pathogen.

The thing we do do in response to pathogens is make very large numbers of the particular antibodies we need.

What happens when an Antigen arrives in the body?

The B-lymphocytes don’t do it all alone. Every B-lymphocyte has a genetically-identical T-lymphocyte. For simplicity I’m going to call B-lymphocytes “B-cells”, and T-lymphocytes “T-cells”.

T-cells can make molecules with binding sites that match those of their matching B-cells’ antibodies. But T-cells’ don’t make and release antibodies - instead they make similar molecules that are anchored in the cell membrane, sticking their antigen-binding-sites out into the tissue fluids.

These proteins are, massively confusingly, called antibody receptors. You must remember that antibody receptors are receptors that have structures similar to antibodies, not receptors for antibodies. It’d be better if they were called antibody-like receptors, but unfortunately they’re not.

The T-cells expose their antibody receptors to the tissue fluids.

If a pathogen passes by, and if it has an antigen that happens to fit that receptor, then the T-cell can bind to it. This then sets off a cascade of signalling that results in replication of the corresponding B-cells, and those B-cells releasing huge amounts of that particular antibody (if there’s one molecule of that antigen about, there are likely many more to be found).

In summary:

T-cells are the look-outs/scouts (using antibody receptors)
B-cells are the antibody factories (releasing antibodies)

(Side note: B-cells have antigen receptors too, but they still need the T-cells to help them develop into full-speed-ahead antibody factories. It’s all a lot more complicated than I’m explaining here, but you don’t need to know every detail for A-level biology.)

How do Antibodies know that an Antigen is “not part of my body”?

They don’t - antibodies are just small protein molecules, they don’t know anything. Any individual antibody will just swoosh around in our tissue fluids and maybe bind something if it can. It doesn’t know what it’s binding.

So, how do we avoid sticking antibodies onto our own body? (N.b. this does happen in auto-immune diseases, causing huge problems.)

B-cells only release antibodies if their corresponding T-cell has caught an antigen (the T-cell signals to them). But B-cells with antibodies that would attack our own bodies never receive such signals. Because their corresponding T-cells are killed before they get the chance.

T-cells mature in the thymus, an organ between the tops of the lungs. Before release into the body, each newly-matured T-cell is tested to make sure it is functional and to check that it doesn’t bind molecules naturally found in our own bodies. If a T-cell fails either test, it is destroyed.

Autoimmune diseases (eg Type 1 diabetes) happen when this system fails and the immune system attacks the body’s own cells.

Immune Memory (ish)

The second time we encounter a pathogen, our immune systems respond much more rapidly, so we don’t tend to get so ill.

This ‘memory’ is possible due to special B-cells, known as memory cells. These cells live longer than usual, so they persist in the body. So we have more B-cells for previously-encountered antigens than for unknown ones. Immunity is a numbers game, and it takes time to replicate immune cells. The more B-cells you start with, the more quickly you can mount an immune response.

So, this ‘memory’ is simply that that we have more B-cells for antigens we’ve previously encountered. Not really a memory, more a case of being better-stocked for more-likely eventualities.

Vaccination: Antigen vs Pathogen

Vaccination is where we are deliberately exposed to an antigen before we meet the pathogen that carries it in real life, so that we develop B memory cells for that antigen and are ready to mount a rapid immune response.

Because our immune system only needs us to have encounted the antigen and not the whole pathogen, vaccination can be carried out very safely. A single antigen is isolated from the pathogen and copies of this are injected. No live pathogen is involved, so there is no risk of infection.

(In the past live or damaged viruses were used for vaccination, but this is now rare.)