The foundations of immunology
Immunology is the study of how a body recognises what does not belong in it and what it does about it. The system it describes has no centre: it is more than a trillion cells, moving, that decide between them what to attack and what to leave alone.
Too little response is immunodeficiency; a response against the body itself is autoimmunity; a response against something harmless is allergy. Cancer partly succeeds by persuading the system to stand down — which is why drugs that release its brakes, first approved in 2011, can work.
Cells that react to the body’s own molecules are mostly deleted while they mature, and those that escape are held in check by regulatory T cells, identified by Shimon Sakaguchi in 1995. The discovery of this peripheral tolerance was recognised with the 2025 Nobel Prize, shared by Sakaguchi, Mary Brunkow and Fred Ramsdell.
After a response, some of the cells that fought it persist for years. A second encounter is met faster and harder. This is the entire basis of vaccination, from Jenner’s cowpox in 1796 to mRNA vaccines in 2020.
Each lymphocyte carries one kind of receptor. An invader is met by the few cells whose receptor happens to fit; those cells multiply, and the rest stay quiet. Macfarlane Burnet proposed this in 1957, and it remains the organising idea of the field.
Antibody and T-cell receptor genes are assembled in each cell by shuffling gene segments — V(D)J recombination, shown by Susumu Tonegawa in 1976. A limited genome yields many millions of different receptors, made before any invader is seen.
Innate immunity acts within hours using receptors for features common to many microbes, such as the Toll-like receptors described in the 1990s. Adaptive immunity — B cells and T cells — takes days, but is specific to the invader and leaves memory behind. Dendritic cells, found by Ralph Steinman in 1973, carry the message from one arm to the other.
A body is a rich habitat, and everything that tries to live in it must be told apart from the body’s own cells. T cells do this by inspecting fragments of protein displayed on MHC molecules. Zinkernagel and Doherty showed in 1974 that a T cell recognises an infected cell only together with the body’s own MHC; that what it reads there is a protein fragment was shown in the 1980s.
Read from the bottom up. Everything above depends on the first problem — telling self from non-self — and most immune disease is that distinction going wrong.