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Portrait of The immune system

Science · Medicine & the body

The immune system

Clonal selection theory, 1957

Medicine — immunology

The body's defence network, conventionally divided into two arms. The innate arm — skin and mucous membranes, phagocytes, natural killer cells, the complement proteins and inflammation — acts within minutes against anything foreign but learns nothing. The adaptive arm, built on B and T lymphocytes, takes days to respond but recognises specific molecular shapes and remembers them, which is why second infections are usually milder and why vaccination works. Its failures are equally instructive: allergy is an overreaction, autoimmune disease is an attack on self, and AIDS is what happens when its coordinating cells are destroyed.

How to spot them

  • ▸Innate versus adaptive: fast and general, or slow, specific and with memory
  • ▸B cells mature in the bone marrow and make antibodies; T cells mature in the thymus
  • ▸Helper T cells carry CD4, cytotoxic T cells carry CD8
  • ▸Five antibody classes: IgG, IgA, IgM, IgD and IgE
  • ▸A long roll of Nobel Prizes: 1908, 1960, 1972, 1984, 1987, 1996, 2011, 2018

Key facts

B cells that mature in the marrow and T cells that mature in a gland behind the sternum

The two lymphocyte lineages; the gland is the thymus, which gives the T its letter

Five classes of the Y-shaped molecule: G, A, M, D and E

The immunoglobulins — IgG is commonest and crosses the placenta, IgE causes allergy

Metchnikoff's roving cell-eaters and Ehrlich's side-chain theory, honoured jointly in 1908 (1908)

The cellular and humoral schools, sharing a Nobel Prize

Köhler and Milstein's hybridomas at the Cambridge LMB, rewarded in 1984 (1975)

Monoclonal antibodies — a single clone making one antibody for ever

Susumu Tonegawa's 1987 prize, for showing how a few hundred gene segments make millions of shapes (1987)

Somatic recombination — the solution to the diversity problem

Macfarlane Burnet's theory of 1957, explaining why the body does not attack itself (1957)

Clonal selection and acquired tolerance; Burnet shared the 1960 Nobel Prize with Peter Medawar

The thymus and the bone marrow as primary organs, the spleen, lymph nodes and tonsils as secondary

Where the cells are made and where they meet antigen

A cascade of about thirty plasma proteins ending in a membrane attack complex

The complement system, part of the innate response

Key ideas

  • Specificity comes from shuffling gene segments, not from storing a gene for every possible antigen: a few hundred segments recombine into billions of receptor shapes.
  • Memory is the point. A first exposure is slow and produces IgM; a second is fast, large and dominated by IgG — the principle every vaccine exploits.
  • Tolerance is learned, not innate: lymphocytes that react strongly to the body's own molecules are deleted or suppressed during development, and autoimmune disease is that process failing.

Quick-fire facts

  • •The innate arm includes physical barriers, neutrophils, macrophages, dendritic cells, natural killer cells, complement and inflammation
  • •The adaptive arm is built on B lymphocytes (antibody-mediated) and T lymphocytes (cell-mediated)
  • •B cells mature in the bone marrow, T cells in the thymus; activated B cells become antibody-secreting plasma cells
  • •Helper T cells carry the CD4 marker, cytotoxic T cells CD8; HIV destroys CD4 cells, which is why AIDS disables the whole system
  • •The five antibody classes are IgG (most abundant, crosses the placenta), IgM (first made, a pentamer), IgA (in secretions and breast milk), IgE (allergy and parasites) and IgD
  • •An antibody is Y-shaped, with two heavy and two light chains and variable regions at the tips that bind the antigen
  • •The major histocompatibility complex, called HLA in humans and encoded on chromosome 6, presents fragments to T cells and determines transplant matching
  • •Metchnikoff and Ehrlich shared the 1908 Nobel Prize; Burnet and Medawar the 1960 prize for acquired tolerance
  • •Edelman and Porter won in 1972 for antibody structure; Jerne, Köhler and Milstein in 1984 for monoclonal antibodies; Tonegawa alone in 1987 for antibody diversity
  • •Doherty and Zinkernagel won in 1996 for MHC restriction; Beutler, Hoffmann and Steinman in 2011 for innate immunity and dendritic cells
  • •Allison and Honjo shared the 2018 prize for checkpoint inhibition, which releases the brakes on T cells to treat cancer
  • •Allergy is an IgE-mediated hypersensitivity; the term anaphylaxis was coined by Charles Richet, who won the 1913 Nobel Prize
  • •Autoimmune diseases include type 1 diabetes, rheumatoid arthritis, lupus and multiple sclerosis

Drill it — 10 cards

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