Hay fever: when your body guards overreact
Two people breathe the same pollen and only one sneezes. Follow the pollen to find out why.
Same pollen, different reaction
Two friends walk across the same grassy field on a warm, windy day. Both breathe in pollen, the fine powder plants use to make seeds (gold). One friend is fine. The other starts sneezing, with a runny nose and itchy eyes. That is hay fever. The pollen is just as harmless for both of them, so what is different? Keep that question in mind: we will follow the pollen to find out.
Hay fever (seasonal allergic rhinitis) is an allergy to pollen from trees, grasses and weeds. Each breath carries pollen into the nose, where it lands on the moist lining (the nasal mucosa, lit here) that warms and filters the air. In most people nothing happens. In people with hay fever, the immune system treats one of the proteins in the pollen as a threat. Symptoms are worst when pollen is in the air: in the UK usually from late March to September, and especially on warm, humid and windy days. Dust mites, mould and pet dander cause the same kind of allergy all year round.
The first meeting leaves a memory
The first time some people breathe in pollen, their body guards make a mistake. Cells in the nose lining carry bits of the pollen to the lymph nodes in the neck (gold), and the nodes decide it is a germ. They make sticky tags called IgE (blue) that fit that pollen exactly, and the tags travel back to the nose lining. Nothing hurts and nobody sneezes yet. The body has simply set a trap for next time.
This is sensitisation. Antigen-presenting cells in the mucosa pick up the pollen allergen and carry it to the nearby lymph nodes, where they steer B cells to make IgE antibodies specific to that allergen. IgE binds to high-affinity receptors (FcεRI) on mast cells, immune cells that live in the lining of the nose, eyes, lungs and skin. The dots only show the direction: the real route from the lining to the nodes is the lymph vessels, which are not in this model. Binding IgE on its own does not set off a mast cell.
Setting the trap
Now we zoom right into the nose lining, onto one cell. This is a mast cell, one of the body guards that live there. The blue Y shapes on its outside are the IgE tags, waiting. Inside, it is packed with little bags (orange) full of a chemical alarm called histamine. Drag to turn the cell around: the tags cover it on every side.
A mast cell carries a large number of FcεRI receptors, and after sensitisation many of them hold pollen-specific IgE. Its cytoplasm is filled with secretory granules holding preformed mediators, histamine among them, ready to be released in seconds. This drawing is schematic: real IgE molecules are far too small to see at this size, and the cell is shown much bigger than the body around it.
Pollen returns
A pollen grain lands on the wet lining and some of its proteins seep out (gold). Each one sticks to two blue tags at once, and that is the signal. The mast cell moves its bags to its edge and empties them. Histamine (orange) spreads out into the lining around it. The scene plays again and again, so watch it as many times as you like.
Pollen grains swell when they get wet and release allergen-carrying material. The allergen binds two or more adjacent IgE on a sensitised mast cell, cross-linking FcεRI, and the cell releases its preformed mediators such as histamine within minutes (the early phase). It also starts making new signals, such as leukotrienes and cytokines, which call in other immune cells: this late phase begins a few hours later and can last a day, which is part of why a blocked nose can linger. The grain is drawn to show where the protein comes from; real grains stay on the surface of the lining.
One alarm, several symptoms
Back out to the face. The histamine sets off three things. The lining of the nose swells and makes extra mucus, so your nose gets blocked and runny. Histamine also tickles the nerves in the lining (orange), and they send a message to the brain that says "get it out": achoo! Pollen lands on your eyes too, and the same alarm there makes the tear glands pour out tears, so your eyes itch and water.
Histamine acts on H1 receptors. On the blood vessels of the mucosa it makes them widen and leak, so the lining swells (congestion). On the mucus glands it drives secretion (a runny nose). On the sensory nerve endings it causes itch and the sneeze: the signal runs back along the maxillary branch of the trigeminal nerve to the brainstem, which fires the sneeze. The same reaction in the thin lining of the eye (allergic conjunctivitis) makes the eyes red, itchy and watery. Antihistamine medicines work by blocking histamine from its H1 receptor, like a key that fits the lock but does not turn it.
Back to the two friends
So why does only one friend sneeze? Because only their body made the IgE mistake the first time, and set the trap. Why some people make that mistake is still being worked out, but it often runs in families: you can inherit a body that is more likely to get allergies, though not a particular allergy, and lots of children with allergic parents never get one. People with hay fever are also more likely to have eczema or asthma. None of this can say for sure who will get it.
Being prone to making IgE against harmless things is called atopy. It clusters in families and in individuals: eczema, food allergy, asthma and allergic rhinitis often occur together, and in many children eczema comes first (the “atopic march”), though whether that is one progression or several groups is debated. Family history raises the chance but predicts nothing for certain. The environment matters too. In 1989 David Strachan noticed that children with more older brothers and sisters were less likely to get hay fever, and suggested early infections might protect them: the “hygiene hypothesis”. Later work linked growing up on farms with less allergy, but no single explanation has held up, so it remains an idea under study, not a rule.