Functions of antibodies

Functions of antibodies

An antibody does no harm by itself. Its arms bind and block; once they have bound, its stem calls in complement, phagocytes and killer cells. The stem also works with no antigen bound: it arms mast cells with IgE, and carries antibody into secretions and across the placenta.

What antibodies do, from neutralising a virus to crossing the gut lining

6 scenes, 0:55

A film in six scenes on a white page, drawn flat and soft like the function figures. First, a broad peach cell fills the bottom of the picture, dark green receptors standing on its surface. A teal virus with knobbed spikes drifts in from the upper right and rests one spike on a receptor. Another drifts in from the left while small green Y-shaped IgG antibodies come in one after another and lock onto its spikes, two spikes to each; coated all round, it hangs above the receptors and drifts back. Next, the khaki surface of a bacterium curves across the top, its amber membrane along its edge and small knobs standing from it. An IgM rises from below, flat, its arms spread in the plane of its disc; near the surface its arms bend up to the knobs, the arms of a third unit rising behind, so that it stands on the surface like a staple. Deep green C1q rises to its stems, then light green C3b appears on the surface round it, spreading outward, and deep green attack complexes push into the membrane and open pores. Then a khaki bacterium, coated by IgG that arrive one by one, above a pale periwinkle macrophage whose cup rises under it; the cup's arms climb round the bacterium, a dark Fc receptor taking hold of each antibody's stem as an arm reaches it, until the arms nearly meet over the top. Then a peach infected cell across the top, viral proteins on its underside each held by IgG; a periwinkle NK cell rises from below until the antibodies' stems rest on its CD16. Two pink granules travel to the top of the NK cell and open, pores of perforin appear in the infected cell's membrane opposite, and small light green granzymes cross the gap and pass through. Then a periwinkle mast cell packed with pale yellow granules, IgE standing round its top on dark FcεRI. Two deep green allergens drift down, each coming to rest on the arms of two neighbouring IgE; granules move to the membrane at the cell's sides, open, and pink histamine spreads out. Last, the gut lining in section: violet mucus with khaki rod bacteria across the top, peach columnar cells with microvilli across the middle, a pale lamina propria with plasma cells and IgA dimers below. A dimer leaves a plasma cell and drifts to a string of light green beads hanging from a cell's base, the receptor pIgR, whose outer part, light green ovals, spreads across the dimer as it binds; a pale yellow vesicle forms round them, crosses the cell turning over, and fuses with the top membrane. The receptor's beads fade below its outer part, which stays across the dimer as the secretory component, a stub left in the membrane, and the secretory IgA rises into the mucus, where two bacteria come to rest on its arms.

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Neutralisation

Scenes

About this film

An antibody acts in several ways. Its arms alone can neutralise a virus or a toxin; its stem calls in complement, the Fc receptors of phagocytes and NK cells, and, for IgE, mast cells; dimeric IgA is carried across the epithelium into the mucus.

Simplified: Not to scale: the antibodies are drawn many times larger against the virus, the bacteria and the cells than they are, and a few stand for many. The virus is drawn small and simple, with a dozen spikes; a real one carries many more. IgM is seen side on, three of its five units in view; C1r, C1s and the steps between C1 and C3 are left out, and one membrane stands for the bacterium's envelope. IgM and IgE are drawn with IgG's thin hinge; in its place each has a whole domain. The Fcγ receptors are drawn as one kind, a ball on a stalk, and only where they hold an antibody, though the macrophage carries them all over; the cup is shown closing in a few seconds. The gap between the two cells is drawn wide, to show the antibodies in it; the granzymes are drawn as loose dots, and the infected cell's death, which takes longer, is not shown. Only the IgE round the top of the mast cell is drawn, though it wears them all over, and granule contents are drawn as a pink core. One dimer is followed across one cell, drawn flat and straight though its two units are bent and tilted against each other; pIgR is drawn as a stalk of three beads, its five outer domains as ovals once they lie across the dimer; the basement membrane is left out.

10 sources
  1. Kumar and Clark's Clinical Medicine, 10th edition. Elsevier, 2021. Chapter 3, Immunity: complement, opsonisation (Fig. 3.3) and natural killer cells.
  2. Silverthorn DU. Human Physiology, An Integrated Approach, 8th edition. Pearson, 2019. Chapter 24, complement (Fig. 24.6), antibody functions and cytotoxic cells.
  3. Forthal DN. Functions of antibodies. Microbiol Spectr. 2014;2(4):AID-0019-2014.
  4. Gillis C, Gouel-Chéron A, Jönsson F, Bruhns P. Contribution of human FcγRs to disease with evidence from human polymorphisms and transgenic animal studies. Front Immunol. 2014;5:254.
  5. Heesterbeek DAC, Bardoel BW, Parsons ES, et al. Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases. EMBO J. 2019;38(4):e99852.
  6. V'kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2021;19(3):155–170.
  7. Keyt BA, Baliga R, Sinclair AM, Carroll SF, Peterson MS. Structure, function, and therapeutic use of IgM antibodies. Antibodies. 2020;9(4):53.
  8. Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18(5):693–704.
  9. de Sousa-Pereira P, Woof JM. IgA: structure, function, and developability. Antibodies. 2019;8(4):57.
  10. Kumar Bharathkar S, Parker BW, Malyutin AG, et al. The structures of secretory and dimeric immunoglobulin A. eLife. 2020;9:e56098.
Contents11 sections

At a glance

  1. An antibody's arms (Fab) bind the antigen; its stem (Fc) binds complement or the Fc receptors of cells, which do the killing. Free IgG and IgM set off little, so the killing comes where antigen has been found. Some receptors hold or carry antibody with no antigen bound: FcεRI arms mast cells with IgE, and pIgR and FcRn carry antibody across cells.
  2. Alone, antibody neutralises: it covers what a toxin, virus or bacterium needs to attach or enter. This needs only the arms. With many binding sites it agglutinates particles into clumps; IgM and secretory IgA do this best.
  3. Complement: C1q binds several Fc held close together, on an IgM bound to a surface or a cluster of bound IgG, and starts the classical pathway. C3b coats the target, C5a calls in neutrophils, and the membrane attack complex lyses some bacteria.
  4. Fc receptors: Fcγ receptors on macrophages and neutrophils engulf IgG-coated microbes (opsonisation); CD16 on NK cells kills IgG-coated infected and tumour cells (ADCC); FcεRI holds IgE on mast cells, and an allergen that links two IgE releases histamine within minutes.
  5. Transport: the polymeric immunoglobulin receptor carries dimeric IgA through epithelial cells into secretions; FcRn carries IgG across the placenta and rescues it from breakdown, so most IgG lasts about three weeks in the blood.
  6. Each class has its jobs: IgM agglutinates and activates complement, IgG does almost everything and crosses the placenta, IgA guards the mucosae, and IgE arms mast cells against worms and in allergy.

Binding first, then acting

Antibodies do no damage themselves. They block, clump and mark, and the destruction is done by others: complement, phagocytes, natural killer cells, mast cells and eosinophils. The two ends of the molecule share the work. The Fab arms bind the epitope; the Fc stem, which differs from class to class, binds the molecules and cells that act.

An antibody bound to its antigen forms an immune complex. Free antibody circulates without setting off complement, and most Fc receptors bind single antibody molecules too weakly to hold them. Many Fc held close together, on a coated microbe or in a complex, bind strongly. So the help an antibody calls arrives where it has found its antigen.

Neutralisation and agglutination need only the arms; complement and the Fc receptors need the Fc. Which functions an antibody has depends on its class and, for IgG, its subclass: as a rule IgG1 and IgG3 bind complement and Fc receptors best, IgG2 and IgG4 less well.

What antibodies do once bound
Three scenes on a pale plate, each in one step. In the first a round teal-green virus, a red coil of genome beaded with protein inside it, is ringed by six small green Y-shaped antibodies, each holding two of the virus's spikes with the tips of its arms, their stems pointing out. Below, the curved top of a peach body cell carries a row of deep green receptors, and the coated virus hangs clear of them. In the second a khaki rod-shaped bacterium is covered all round by twelve small antibodies, arms on the bacterium and stems out. A large pale blue macrophage below has closed a cup round it, its two arms reaching up past the bacterium's ends; small deep green receptors on the inside of the cup hold the stems of the antibodies they touch. The macrophage has a bean-shaped nucleus and a few pink lysosomes. In the third the khaki bacterium fills the top, its membrane an amber band along its lower edge. Below it hangs one IgM: two units at the sides lie flat, their stems meeting in a central disc, a dark green J chain at the front of the ring, their arm pairs bent up to small knobs on the surface, and a third unit's arms rise between them from behind. Under the disc C1q holds on with six deep green heads, their stalks gathered into one stem. Small light green C3b ovals lie on the surface round it, and at each side two deep green pillars cross the membrane, the walls of a pore. Step 1 of 3: Neutralisation. Antibodies on the virus's spikes keep it from binding the receptor it enters by, so it cannot infect a cell. Antibody against a toxin works the same way.

Step 1 of 3Neutralisation. Antibodies on the virus's spikes keep it from binding the receptor it enters by, so it cannot infect a cell. Antibody against a toxin works the same way.

Point at a name or a part to light it.

An antibody's arms bind; its stem decides what follows. Bound to a virus or a toxin, the arms alone can stop it. Bound to a bacterium, the stems are handles for phagocytes' Fc receptors and, in clusters, for C1q, which starts complement.

Simplified: not to scale, and each scene at its own: a bacterium is many times wider than the antibodies on it; the virus drawn small and simple, a dozen spikes; a real one carries many more; the Fcγ receptors drawn as one kind, a ball on a stalk; there are several, with different jobs; IgM side on, three of its five units in view, the others behind; IgM drawn with IgG's thin hinge; in its place it has a whole domain; C1r, C1s and the steps between C1 and C3 left out; one membrane stands for the bacterium's envelope, which in a Gram-negative bacterium has two.

7 sources
  1. Kumar and Clark's Clinical Medicine, 10th edition. Elsevier, 2021. Chapter 3, Immunity: complement, opsonisation (Fig. 3.3, Box 3.4) and immunoglobulins.
  2. Silverthorn DU. Human Physiology, An Integrated Approach, 8th edition. Pearson, 2019. Chapter 24, complement (Fig. 24.6) and antibody functions.
  3. Forthal DN. Functions of antibodies. Microbiol Spectr. 2014;2(4):AID-0019-2014.
  4. Gillis C, Gouel-Chéron A, Jönsson F, Bruhns P. Contribution of human FcγRs to disease with evidence from human polymorphisms and transgenic animal studies. Front Immunol. 2014;5:254.
  5. Heesterbeek DAC, Bardoel BW, Parsons ES, et al. Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases. EMBO J. 2019;38(4):e99852.
  6. V'kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2021;19(3):155–170.
  7. Keyt BA, Baliga R, Sinclair AM, Carroll SF, Peterson MS. Structure, function, and therapeutic use of IgM antibodies. Antibodies. 2020;9(4):53.

Neutralisation

An antibody that covers the molecules a microbe or toxin needs stops it without help. This is neutralisation.

  • Toxins. Antibody bound to a bacterial toxin keeps it off our cells. The diphtheria vaccine is an inactivated toxin: it raises antibody that neutralises the real toxin when the bacteria make it.
  • Viruses. Antibody against a virus's attachment protein keeps it from its receptor, as antibody against the gp120 of HIV keeps it from CD4. Other antibodies stop the viral and cell membranes from fusing, or the virus from uncoating once inside. Usually several antibodies must bind one virion to neutralise it.
  • Bacteria and other microbes. Antibody against adhesins, often on the bacteria's pili and fimbriae, keeps them from sticking to epithelium, the first step of most infections. Secretory IgA in breast milk does this for gut bacteria in the infant.

A Fab fragment can be enough. Neutralisation stops an infection before it starts, and like antibody in general it works best outside cells, on toxins and on viruses that have not yet entered a cell.

Agglutination

An IgG has two binding sites, a secretory IgA four and an IgM pentamer ten. Binding epitopes on different particles links them, so bacteria, viruses or red cells are drawn into clumps: agglutination. Clumped microbes reach fewer cells, are caught in mucus and are taken up by phagocytes more easily. IgM and the polymeric IgA, with their many sites, agglutinate best. On the mucosae secretory IgA holds microbes in the mucus, to be swept away before they reach the epithelium, a defence called immune exclusion.

Complement

Antibody bound to a surface starts the classical pathway of complement. Its first component, C1q, has six heads and holds fast only where several Fc stand close together.

  • IgM in the blood is a flat disc. When it binds a surface its arms bend down onto it, like a staple, and its Fc are presented together. This is why IgM activates complement far better than IgG.
  • IgG must bind close together: bound molecules gather through their Fc into rings of six, a platform for C1q. IgG3 and IgG1 do this best. IgG2 does it only where antigen is dense, as on bacterial polysaccharide, and IgG4 hardly binds C1q.
  • IgA, IgE and IgD do not activate the classical pathway.

Once C1 is active, the cascade runs as in the innate response, and its products serve the antibody. C3b coats the target, a second handle for phagocytes beside the Fc. C5a above all draws in neutrophils, and C3a and C5a both make vessels leaky. The membrane attack complex (C5b to C9) punches holes in the outer membrane of some bacteria, notably Neisseria. Complement also helps clear immune complexes from the blood: C3b on a complex binds complement receptor 1 on red cells, which hold it until tissue macrophages take it off.

Fc receptors

Most cells that act for antibodies hold them by their Fc. Each class has its own receptors, and each receptor its own cells.

ReceptorBindsMain cellsWhat it does
FcγRI (CD64)IgG, even single moleculesmonocytes, macrophages, dendritic cells; neutrophils when inflamedphagocytosis
FcγRIIa (CD32a)IgG in complexesall myeloid cells: monocytes, macrophages, neutrophils, eosinophils, mast cellsphagocytosis, activation
FcγRIIb (CD32b)IgG in complexesB cells, basophils, some macrophagesinhibits the cell
FcγRIIIa (CD16a)IgG in complexesNK cells, monocytes, macrophagesADCC
FcγRIIIb (CD16b)IgG in complexesneutrophilswith FcγRIIa, gathers neutrophils where immune complexes lie
FcεRIIgE, even single moleculesmast cells, basophilsdegranulation
FcαRI (CD89)IgAneutrophils, monocytes, macrophagesphagocytosis, activation
Polymeric Ig receptordimeric IgA, pentameric IgMmucosal epithelial cellscarries them into secretions
FcRnIgG and albumin, at acid pHplacenta, endothelium, epithelia, blood cellscarries IgG across cells; saves it from breakdown

High-affinity receptors (FcγRI, FcεRI) can hold a single free antibody; the other Fcγ receptors and FcαRI hold well only antibody gathered in complexes or on a surface. The transport receptors, pIgR and FcRn, carry free antibody. Most Fc receptors switch the cell on. FcγRIIb switches it off: on B cells, immune complexes bound to it hold back their activation.

Opsonisation and phagocytosis

To opsonise is to coat a particle so a phagocyte takes it more readily. Many bacteria, above all those with a polysaccharide capsule, slip past phagocytes on their own. Coated with IgG, they are gripped by the Fcγ receptors of macrophages and neutrophils; coated also with C3b, they are gripped by complement receptors as well. The phagocyte wraps the microbe, closes it into a phagosome and kills it there.

Opsonisation is why antibody and complement matter most against capsulated bacteria such as pneumococcus and Haemophilus influenzae, and why the spleen, full of macrophages that take coated bacteria from the blood, matters too. Against meningococcus, another capsulated bacterium, killing by complement matters more than phagocytosis.

Killing by NK cells: ADCC

Natural killer cells carry CD16 (FcγRIIIa). When IgG coats a cell, a virus-infected cell showing viral proteins on its surface or a tumour cell, CD16 binds the Fc and the NK cell releases perforin, which opens pores, and granzymes, which drive the target into apoptosis. This is antibody-dependent cellular cytotoxicity (ADCC). The antibody brings the specificity, the NK cell the killing. Antibodies used against tumours, such as rituximab against CD20 on B lymphoma cells, work partly this way.

Eosinophils, macrophages and neutrophils can kill antibody-coated targets too. Worms are far too large to swallow: coated with IgE or IgG, the larvae of Schistosoma and other helminths are attacked by eosinophils, which release their toxic granule proteins onto the worm's surface.

IgE, mast cells and eosinophils

IgE is the scarcest antibody in the blood, and it does its work bound to cells. Mast cells in the tissues and basophils in the blood bind it by its Fc to FcεRI, which holds IgE so tightly that it stays on the cell with no antigen bound. The cell is then armed with receptors made by B cells, for whatever antigens they recognise.

When an antigen with two or more epitopes binds two neighbouring IgE, it draws their receptors together. Cross-linking, not binding alone, is the signal. Within minutes the mast cell releases what its granules hold, histamine, proteases such as tryptase, and heparin, then makes prostaglandin D2 and leukotrienes. Vessels dilate and leak, and the smooth muscle of the airways and gut contracts. Against worms this is part of the defence. Against pollen, food or venom it is allergy, immediate (type I) hypersensitivity, from hay fever and urticaria to anaphylaxis. A late phase follows hours later, as eosinophils and T cells arrive.

Cells armed by antibody
Two scenes on a pale plate, one in each step. In the first a large peach body cell fills the top: it has a lavender nucleus and three small red coils of new viral genome, beaded with protein, inside, and teal-green viral proteins stand on stalks from its lower surface. Five small green Y-shaped IgG hang from them, each holding two viral proteins with the tips of its arms, stems down. Below, a broad pale blue NK cell presses its flat top against the stems, small deep green CD16 receptors gripping each one. Pink granules gather at the top of the NK cell; two have opened onto the gap, small light green granzyme dots cross it, and at each of those places two short deep green pillars of perforin make a pore through the infected cell's membrane. In the second a large oval pale blue mast cell is packed with pale yellow granules, each with a pink core, round a blue nucleus. Seven green IgE stand round its top on short deep green FcεRI receptors, arms out. Deep green lumpy allergen molecules float above; two sit between neighbouring IgE, held by the arms of both. At the sides of the cell four granules have opened at the membrane, and pink histamine dots spill out of them. Step 1 of 2: NK cells kill coated cells (ADCC). IgG binds viral proteins on an infected cell. CD16 on an NK cell grips the stems, and the NK cell empties perforin and granzymes onto the cell, which dies.

Step 1 of 2NK cells kill coated cells (ADCC). IgG binds viral proteins on an infected cell. CD16 on an NK cell grips the stems, and the NK cell empties perforin and granzymes onto the cell, which dies.

Point at a name or a part to light it.

Fc receptors let a cell borrow an antibody's aim. An NK cell can kill an infected cell that IgG has coated; a mast cell, already wearing IgE, empties its granules within minutes of an allergen joining two of them.

Simplified: not to scale, and each scene at its own; the gap between the two cells drawn wide, to show the antibodies in it; granzymes drawn as loose dots; they leave the granule bound to other proteins; only the IgE round the top of the mast cell drawn; it wears them all over; IgE drawn with IgG's thin hinge; in its place it has a whole domain; granule contents drawn as a pink core; each holds many mediators besides histamine; eosinophils, basophils and macrophages, which also kill or release through Fc receptors, left out.

6 sources
  1. Kumar and Clark's Clinical Medicine, 10th edition. Elsevier, 2021. Chapter 3, Immunity: natural killer cells.
  2. Silverthorn DU. Human Physiology, An Integrated Approach, 8th edition. Pearson, 2019. Chapter 24, antibody functions and cytotoxic cells.
  3. V'kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2021;19(3):155–170.
  4. Gillis C, Gouel-Chéron A, Jönsson F, Bruhns P. Contribution of human FcγRs to disease with evidence from human polymorphisms and transgenic animal studies. Front Immunol. 2014;5:254.
  5. Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18(5):693–704.
  6. Keyt BA, Baliga R, Sinclair AM, Carroll SF, Peterson MS. Structure, function, and therapeutic use of IgM antibodies. Antibodies. 2020;9(4):53.

Secretory IgA at the mucosae

More IgA is made than all the other classes together, much of it by plasma cells under the mucosae of the gut, airways and glands. They secrete it as a dimer, two units joined by the J chain, into the lamina propria. To reach the lumen it has to cross the epithelium, which it cannot do alone:

  1. 1

    Binding

    The polymeric immunoglobulin receptor (pIgR) on the basolateral surface of the epithelial cell binds the dimer where its J chain joins the stems, gripping both; IgA without a J chain is not carried. The receptor's outer part spreads across one face of the dimer.

  2. 2

    Transcytosis

    The cell takes receptor and IgA into a vesicle and carries it across to the apical surface.

  3. 3

    Release

    At the apical surface the receptor is cut below its outer part, which stays bound to the IgA as the secretory component, and the complex, secretory IgA, is released into the mucus.

How IgA crosses the gut lining
A section through the gut lining on a pale plate. Across the top lies the lumen, a pale violet wash of mucus with khaki rod-shaped bacteria in it. Across the middle stand tall peach epithelial cells side by side, a fringe of microvilli on top, a small dark tight junction where neighbours meet just below it, and a lavender nucleus low in each. Below them is the pale lamina propria. In it, at the lower left, a pale blue plasma cell with its nucleus to one side and violet arcs of rough ER, and near it two small IgA dimers: two green Y-shaped units joined stem to stem, a dark green J chain between them. On the base of each epithelial cell hangs a short string of three light green beads, the receptor pIgR; under the middle cell one holds a dimer, its outer part, five light green ovals, spread across the dimer's face where the J chain joins the stems. In the second step a pale yellow vesicle has appeared in the middle cell, carrying a dimer up on its receptor, the receptor's outer part across it. In the third a dimer has reached the lumen, the receptor's outer part still across it as the secretory component, each of its two units holding a bacterium, and a short stub of the receptor is left in the cell's top membrane. Step 1 of 3: Binding. A plasma cell secretes dimeric IgA. pIgR on the base of an epithelial cell binds a dimer, its outer part gripping the J chain and the stems beside it.

Step 1 of 3Binding. A plasma cell secretes dimeric IgA. pIgR on the base of an epithelial cell binds a dimer, its outer part gripping the J chain and the stems beside it.

Point at a name or a part to light it.

The epithelium carries IgA across itself. Plasma cells under it make dimers; pIgR takes them from the base to the top, and its cut outer part stays on as the secretory component, which helps the IgA last in the gut.

Simplified: not to scale: the antibodies are drawn many times larger against the cells and bacteria; pIgR drawn as a stalk of three beads, its five outer domains as ovals once they lie across a dimer; a waiting receptor's outer domains, folded together, are not drawn; the dimer drawn flat and straight; its two units are bent and tilted against each other; one dimer drawn at each stage of the way, side by side, though in the gut many cross each cell at once; the basement membrane under the epithelium left out; the mucus drawn as one even layer.

3 sources
  1. de Sousa-Pereira P, Woof JM. IgA: structure, function, and developability. Antibodies. 2019;8(4):57.
  2. Kumar Bharathkar S, Parker BW, Malyutin AG, et al. The structures of secretory and dimeric immunoglobulin A. eLife. 2020;9:e56098.
  3. Keyt BA, Baliga R, Sinclair AM, Carroll SF, Peterson MS. Structure, function, and therapeutic use of IgM antibodies. Antibodies. 2020;9(4):53.

In the lumen secretory IgA neutralises toxins and viruses, keeps bacteria from the epithelium and holds them in the mucus. It does all this without setting off complement, so it protects without inflaming the gut wall it lies on. It works even on its way through: IgA meeting a virus inside the epithelial cell can stop it there. Secretory IgA is also the main antibody of breast milk, and in a breast-fed baby's gut it keeps bacteria from the epithelium.

IgG across the placenta, and FcRn

The fetus makes little antibody of its own. IgG is the only class that crosses the placenta in useful amounts, carried by the neonatal Fc receptor (FcRn) of the syncytiotrophoblast. Transfer starts at about 13 weeks and rises steadily, and most of the baby's IgG arrives in the last four weeks. At term the baby's IgG is usually higher than its mother's, by a fifth to nearly a third. IgG1 crosses best, IgG2 least. A baby born early has less.

This maternal IgG protects the newborn against the infections the mother is immune to for the first months, until it is broken down; the baby's own antibody production rises meanwhile. The same transfer carries harmful maternal IgG: the antibodies of a mother with myasthenia gravis can cause transient weakness in her newborn.

FcRn keeps working for life. Endothelial cells take in plasma constantly in small vesicles, and the proteins in them are bound for the lysosomes. In the acid of the endosome, FcRn binds IgG and albumin, carries them back to the cell surface and lets them go at the neutral pH of the blood. This rescue is why most IgG, and albumin, last about three weeks in the blood, against a week at most for IgA and most other plasma proteins. The rescue can be saturated: a large dose of IgG speeds the loss of the body's own.

when IgG transfer across the placenta begins
13weeks of pregnancy
the half-life of IgG, kept long by FcRn
21days
on an IgM pentamer, the best agglutinator
10binding sites

Which class does what

IgGIgMIgAIgEIgD
Neutralises+++++ (secretions)
Agglutinates++++++ (secretory)
Classical complement++ (IgG3, IgG1)+++
Opsonises (Fc receptors)+++ (FcαRI)
ADCC by NK cells++
Arms mast cells and basophils++
Crosses the placenta++
Carried into secretions+++
Main placeblood and tissuesblood, first responsemucosae, milkon mast cellson naive B cells

A first response to an antigen is slow, one to two weeks, and its first antibodies are IgM. Its B cells then switch, guided by T cells, to IgG, IgA or IgE, keeping the same variable region. A second response is faster and larger, mostly IgG of higher affinity, which is why the second dose of a vaccine, and the second meeting with a microbe, work better than the first.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1A Fab fragment against a virus's attachment protein still protects cells in culture. Which function has it kept?

2Why does IgM activate the classical complement pathway far better than IgG?

3Which receptor lets a natural killer cell kill a target cell coated with IgG?

4A mast cell carries IgE against birch pollen on its FcεRI. What makes it degranulate?

5A boy with X-linked agammaglobulinaemia, who has no B cells, stays well for his first months and then has repeated bacterial infections. Why the delay?

6How does dimeric IgA made in the lamina propria reach the gut lumen?