-
66 Scientific American September 2000 Edible Vaccines
Vaccines have accomplished near miracles inthe fight against
infectious disease. They haveconsigned smallpox to history and
should soondo the same for polio. By the late 1990s an
internationalcampaign to immunize all the world’s children
againstsix devastating diseases was reportedly reaching 80 per-cent
of infants (up from about 5 percent in the mid-1970s) and was
reducing the annual death toll fromthose infections by roughly
three million.
Yet these victories mask tragic gaps in delivery. The 20percent
of infants still missed by the six vaccines—againstdiphtheria,
pertussis (whooping cough), polio, measles,tetanus and
tuberculosis—account for about two millionunnecessary deaths each
year, especially in the most re-mote and impoverished parts of the
globe. Upheavals inmany developing nations now threaten to erode
the ad-vances of the recent past, and millions still die from
infec-tious diseases for which immunizations are
nonexistent,unreliable or too costly.
This situation is worrisome not only for the places thatlack
health care but for the entire world. Regions harbor-ing infections
that have faded from other areas are likebombs ready to explode.
When environmental or socialdisasters undermine sanitation systems
or displace com-munities—bringing people with little immunity into
con-tact with carriers—infections that have been long gonefrom a
population can come roaring back. Further, as in-ternational travel
and trade make the earth a smallerplace, diseases that arise in one
locale are increasinglypopping up continents away. Until everyone
has routineaccess to vaccines, no one will be entirely safe.
In the early 1990s Charles J. Arntzen, then at TexasA&M
University, conceived of a way to solve many ofthe problems that
bar vaccines from reaching all toomany children in developing
nations. Soon after learningof a World Health Organization call for
inexpensive,oral vaccines that needed no refrigeration, Arntzen
visit-ed Bangkok, where he saw a mother soothe a crying
by William H. R. Langridge
Edible Vaccines
FOODS UNDER STUDY as alternatives to injectable vac-
cines include bananas, potatoes and tomatoes, as well as
lettuce, rice, wheat, soybeans and corn.
One day children may get immunized by munchingon foods instead
of enduring shots. More
important, food vaccines might save millions whonow die for lack
of access to traditional inoculants
JOH
NSO
N &
FA
NC
HER
Copyright 2000 Scientific American, Inc.
-
baby by offering a piece of banana. Plant biologists had
al-ready devised ways of introducing selected genes (the
blue-prints for proteins) into plants and inducing the altered,
or“transgenic,” plants to manufacture the encoded proteins.Perhaps,
he mused, food could be genetically engineered toproduce vaccines
in their edible parts, which could then beeaten when inoculations
were needed.
The advantages would be enormous. The plants could begrown
locally, and cheaply, using the standard growingmethods of a given
region. Because many food plants can beregenerated readily, the
crops could potentially be producedindefinitely without the growers
having to purchase moreseeds or plants year after year. Homegrown
vaccines wouldalso avoid the logistical and economic problems posed
byhaving to transport traditional preparations over long
dis-tances, keeping them cold en route and at their
destination.And, being edible, the vaccines would require no
syringes—which, aside from costing something, can lead to
infectionsif they become contaminated.
Efforts to make Arntzen’s inspired vision a reality are
stillquite preliminary. Yet studies carried out in animals over
thepast 10 years, and small tests in people, encourage hope
thatedible vaccines can work. The research has also fueled
spec-ulation that certain food vaccines might help suppress
au-toimmunity—in which the body’s defenses mistakenly attacknormal,
uninfected tissues. Among the autoimmune disor-ders that might be
prevented or eased are type I diabetes (thekind that commonly
arises during childhood), multiple scle-rosis and rheumatoid
arthritis.
By Any Other Name …
Regardless of how vaccines for infectious diseases are de-
livered, they all have the same aim: priming the immunesystem to
swiftly destroy specific disease-causing agents, orpathogens,
before the agents can multiply enough to causesymptoms.
Classically, this priming has been achieved by pre-senting the
immune system with whole viruses or bacteriathat have been killed
or made too weak to proliferate much.
On detecting the presence of a foreign organism in a vac-cine,
the immune system behaves as if the body were underattack by a
fully potent antagonist. It mobilizes its variousforces to root out
and destroy the apparent invader—target-ing the campaign to
specific antigens (proteins recognized asforeign). The acute
response soon abates, but it leaves be-hind sentries, known as
“memory” cells, that remain onalert, ready to unleash whole armies
of defenders if the realpathogen ever finds its way into the body.
Some vaccines
provide lifelong protection; others (such as those for
choleraand tetanus) must be readministered periodically.
Classic vaccines pose a small but troubling risk that thevaccine
microorganisms will somehow spring back to life,causing the
diseases they were meant to forestall. For thatreason, vaccine
makers today favor so-called subunit prepa-rations, composed
primarily of antigenic proteins divorcedfrom a pathogen’s genes. On
their own, the proteins have noway of establishing an infection.
Subunit vaccines, however,are expensive, in part because they are
produced in culturesof bacteria or animal cells and have to be
purified out; theyalso need to be refrigerated.
Food vaccines are like subunit preparations in that they
areengineered to contain antigens but bear no genes that
wouldenable whole pathogens to form. Ten years ago Arntzen
un-derstood that edible vaccines would therefore be as safe
assubunit preparations while sidestepping their costs and de-mands
for purification and refrigeration. But before he andothers could
study the effects of food vaccines in people, theyhad to obtain
positive answers to a number of questions.Would plants engineered
to carry antigen genes producefunctional copies of the specified
proteins? When the foodplants were fed to test animals, would the
antigens be de-graded in the stomach before having a chance to act?
(Typi-cal subunit vaccines have to be delivered by injection
precise-ly because of such degradation.) If the antigens did
survive,would they, in fact, attract the immune system’s
attention?And would the response be strong enough to defend the
ani-mals against infection?
Additionally, researchers wanted to know whether ediblevaccines
would elicit what is known as mucosal immunity.Many pathogens enter
the body through the nose, mouth orother openings. Hence, the first
defenses they encounter arethose in the mucous membranes that line
the airways, the di-gestive tract and the reproductive tract; these
membranesconstitute the biggest pathogen-deterring surface in the
body.When the mucosal immune response is effective, it
generatesmolecules known as secretory antibodies that dash into
the
Edible Vaccines Scientific American September 2000 67
PHO
TOG
RAPH
S BY
FO
REST
MC
MU
LLIN
BANANA TREES AND TOMATO PLANTS growing at the
Boyce Thompson Institute for Plant Research at Cornell Uni-
versity have been genetically engineered to produce vaccines
in
their fruit. Bananas are particularly appealing as vaccines
be-
cause they grow widely in many parts of the developing
world,
can be eaten raw and are liked by most children.
Copyright 2000 Scientific American, Inc.
-
cavities of those passageways, neutraliz-ing any pathogens they
find. An effec-tive reaction also activates a systemic re-sponse,
in which circulating cells of theimmune system help to destroy
invadersat distant sites.
Injected vaccines initially bypass mu-cous membranes and
typically do a poorjob of stimulating mucosal immune re-sponses.
But edible vaccines come intocontact with the lining of the
digestivetract. In theory, then, they would activateboth mucosal
and systemic immunity.That dual effect should, in turn, help
im-prove protection against many danger-ous microorganisms,
including, impor-tantly, the kinds that cause diarrhea.
Those of us attempting to developfood vaccines place a high
priority oncombating diarrhea. Together the maincauses—the Norwalk
virus, rotavirus,Vibrio cholerae (the cause of cholera)and
enterotoxigenic Escherichia coli (atoxin-producing source of
“traveler’sdiarrhea”)—account for some threemillion infant deaths a
year, mainly indeveloping nations. These pathogensdisrupt cells of
the small intestine inways that cause water to flow from theblood
and tissues into the intestine. Theresulting dehydration may be
combatedby delivering an intravenous or oral so-lution of
electrolytes, but it often turnsdeadly when rehydration therapy is
notan option. No vaccine practical forwide distribution in the
developing na-
tions is yet available to prevent these ills.By 1995 researchers
attempting to an-
swer the many questions before themhad established that plants
could indeedmanufacture foreign antigens in theirproper
conformations. For instance,Arntzen and his colleagues had
intro-duced into tobacco plants the gene fora protein derived from
the hepatitis Bvirus and had gotten the plants to syn-thesize the
protein. When they injectedthe antigen into mice, it activated
thesame immune system components thatare activated by the virus
itself. (Hep-atitis B can damage the liver and con-tribute to liver
cancer.)
Green Lights on Many Fronts
But injection is not the aim; feedingis. In the past five years
experimentsconducted by Arntzen (who moved tothe Boyce Thompson
Institute for PlantResearch at Cornell University in 1995)and his
collaborators and by my groupat Loma Linda University have
demon-strated that tomato or potato plantscan synthesize antigens
from the Nor-walk virus, enterotoxigenic E. coli, V.cholerae and
the hepatitis B virus. More-over, feeding antigen-laced tubers
orfruits to test animals can evoke mucosaland systemic immune
responses that ful-ly or partly protect animals from subse-quent
exposure to the real pathogens or,in the case of V. cholerae and
enterotox-
igenic E. coli, to microbial toxins. Edi-ble vaccines have also
provided laborato-ry animals with some protection againstchallenge
by the rabies virus, Helicobac-ter pylori (a bacterial cause of
ulcers)and the mink enteric virus (which doesnot affect
humans).
It is not entirely surprising that anti-gens delivered in plant
foods survive thetrip through the stomach well enoughto reach and
activate the immune sys-tem. The tough outer wall of plant
cellsapparently serves as temporary armorfor the antigens, keeping
them relativelysafe from gastric secretions. When thewall finally
begins to break up in the in-testines, the cells gradually release
theirantigenic cargo.
Of course, the key question is whetherfood vaccines can be
useful in people.The era of clinical trials for this technol-ogy is
just beginning. Nevertheless, Arnt-zen and his collaborators
obtained reas-suring results in the first published hu-man trial,
involving about a dozensubjects. In 1997 volunteers who atepieces
of peeled, raw potatoes contain-ing a benign segment of the E. coli
toxin(the part called the B subunit) displayedboth mucosal and
systemic immune re-sponses. Since then, the group has alsoseen
immune reactivity in 19 of 20 peo-ple who ate a potato vaccine
aimed atthe Norwalk virus. Similarly, after Hil-ary Koprowski of
Thomas JeffersonUniversity fed transgenic lettuce carrying
68 Scientific American September 2000 Edible Vaccines
JARE
D S
CH
NEI
DM
AN
DES
IGN1 Cut leaf. 2 Expose leaf to bacte-
ria carrying an antigengene and an antibiotic-resistance
gene.Allowbacteria to deliver thegenes into leaf cells.
3 Expose leaf to an anti-biotic to kill cells that lackthe new
genes. Wait forsurviving (gene-altered)cells to multiply and forma
clump (callus).
4 Allow callus to sproutshoots and roots.
5 Put in soil. Within three months, the plantlets will grow into
plants bearing antigen-laden vaccine potatoes.
BACTERIAL CELL PLANT CELL
PLASMID
GENE TRANSFER
ANTIGEN GENEDNA
ANTIBIOTIC-RESISTANCE
GENEBACTERIAL SUSPENSION
ANTIBIOTIC MEDIUM
DEAD CELL CALLUS
VACCINEPOTATOES
One way of generating edible vaccines relies on thebacterium
Agrobacterium tumefaciens to deliver intoplant cells the genetic
blueprints for viral or bacterial
“antigens”—proteins that elicit a targeted immuneresponse in the
recipient.The diagram illustrates theproduction of vaccine
potatoes.
HOW TO MAKE AN EDIBLE VACCINE
Copyright 2000 Scientific American, Inc.
-
Edible Vaccines Scientific American September 2000 69
a hepatitis B antigen to three volunteers,two of the subjects
displayed a good sys-temic response. Whether edible vaccinescan
actually protect against human dis-ease remains to be determined,
however.
Still to Be Accomplished
In short, the studies completed so farin animals and people have
provideda proof of principle; they indicate thatthe strategy is
feasible. Yet many issuesmust still be addressed. For one,
theamount of vaccine made by a plant islow. Production can be
increased in dif-ferent ways—for instance, by linkingantigen genes
with regulatory elementsknown to help switch on the genes
morereadily. As researchers solve that chal-lenge, they will also
have to ensure thatany given amount of a vaccine food pro-vides a
predictable dose of antigen.
Additionally, workers could try to en-hance the odds that
antigens will activatethe immune system instead of passingout of
the body unused. General stimula-tors (adjuvants) and better
targeting tothe immune system might compensate inpart for low
antigen production.
One targeting strategy involves linkingantigens to molecules
that bind well toimmune system components known asM cells in the
intestinal lining. M cellstake in samples of materials that
haveentered the small intestine (includingpathogens) and pass them
to other cellsof the immune system, such as antigen-presenting
cells. Macrophages and oth-er antigen-presenting cells chop up
theiracquisitions and display the resultingprotein fragments on the
cell surface. Ifwhite blood cells called helper T lym-phocytes
recognize the fragments asforeign, they may induce B lympho-cytes
(B cells) to secrete neutralizing an-tibodies and may also help
initiate abroader attack on the perceived enemy.
It turns out that an innocuous seg-ment of the V. cholerae
toxin—the Bsubunit—binds readily to a molecule onM cells that
ushers foreign material intothose cells. By fusing antigens from
oth-er pathogens to this subunit, it shouldbe possible to improve
the uptake ofantigens by M cells and to enhance im-mune responses
to the added antigens.The B subunit also tends to associatewith
copies of itself, forming a dough-
nut-shaped, five-membered ring with ahole in the middle. These
features raisethe prospect of producing a vaccinethat brings
several different antigens toM cells at once—thus potentially
ful-fulling an urgent need for a single vac-cine that can protect
against multiplediseases simultaneously.
Researchers are also grappling withthe reality that plants
sometimes growpoorly when they start producing largeamounts of a
foreign protein. One solu-tion would be to equip plants with
reg-ulatory elements that cause antigen genesto turn on—that is,
give rise to the encod-ed antigens—only at selected times (suchas
after a plant is nearly fully grown oris exposed to some outside
activator mol-ecule) or only in its edible regions. Thiswork is
progressing.
Further, each type of plant poses itsown challenges. Potatoes
are ideal inmany ways because they can be propa-gated from “eyes”
and can be stored forlong periods without refrigeration.
Butpotatoes usually have to be cooked to bepalatable, and heating
can denature pro-teins. Indeed, as is true of tobacco
plants,potatoes were not initially intended to be
JARE
D S
CH
NEI
DM
AN
DES
IGN
1 M cells pass the antigen tomacrophages
and B cells
2 Macrophages display
pieces of the antigen
to helperT cells
3 T cells stimulate B cells and seek out antigens at distant
sites
4 Activated B cells make and release antibodies
able toneutralize
the antigen
1 Memoryhelper T cellsprod cytotoxic T cells to attackinfected
cells
3 Antibodiesquickly neutralize the invader
2 Memory helper T cells swiftly stimulate antibody secretion
HELPER T CELL
MACROPHAGE CYTOTOXICT CELL
MEMORYHELPER T CELL
MEMORY B CELL
INFECTEDCELL
WHEN A DISEASE AGENT APPEARSINITIAL RESPONSE
STIMULATORY SECRETIONS
M CELL ANTIBODY
B CELL
ANTIGEN FROMVACCINE
ARRIVING VIRUS
Copyright 2000 Scientific American, Inc.
-
used as vaccine vehicles; they were stud-ied because they were
easy to manipu-late. Surprisingly, though, some kinds ofpotatoes
are actually eaten raw in SouthAmerica. Also, contrary to
expectations,cooking of potatoes does not always de-stroy the full
complement of antigen. Sopotatoes may have more practical meritthan
most of us expected.
Bananas need no cooking and aregrown widely in developing
nations, butbanana trees take a few years to mature,and the fruit
spoils fairly rapidly afterripening. Tomatoes grow more quicklyand
are cultivated broadly, but they toomay rot readily. Inexpensive
methodsof preserving these foods—such as dry-ing—might overcome the
spoilage prob-
lem. Among the other foods under con-sideration are lettuce,
carrots, peanuts,rice, wheat, corn and soybeans.
In another concern, scientists need tobe sure that vaccines
meant to enhanceimmune responses do not backfire andsuppress
immunity instead. Researchinto a phenomenon called oral
tolerancehas shown that ingesting certain pro-teins can at times
cause the body to shutdown its responses to those proteins.
Todetermine safe, effective doses and feed-ing schedules for edible
vaccines, manu-facturers will need to gain a better han-dle on the
manipulations that influencewhether an orally delivered antigen
willstimulate or depress immunity.
A final issue worth studying is whetherfood vaccines ingested by
mothers canindirectly vaccinate their babies. In the-ory, a mother
could eat a banana or twoand thus trigger production of antibod-ies
that would travel to her fetus via theplacenta or to her infant via
breast milk.
Nonscientific challenges accompanythe technical ones. Not many
pharma-ceutical manufacturers are eager to sup-port research for
products targeted pri-marily to markets outside the lucrativeWest.
International aid organizations andsome national governments and
philan-thropies are striving to fill the gap, butthe effort to
develop edible vaccines re-mains underfunded.
In addition, edible vaccines fall underthe increasingly
unpopular rubric of “ge-netically modified” plants. Recently
aBritish company (Axis Genetics) thatwas supporting studies of
edible vaccinesfailed; one of its leaders lays at leastpart of the
blame on investor worryabout companies involved with geneti-cally
engineered foods. I hope, however,that these vaccines will avoid
seriouscontroversy, because they are intendedto save lives and
would probably beplanted over much less acreage than oth-er food
plants (if they are raised outsideof greenhouses at all). Also, as
drugs,they would be subjected to closer scruti-ny by regulatory
bodies.
Fighting Autoimmunity
Consideration of one of the chal-lenges detailed here—the risk
of in-ducing oral tolerance—has recently ledmy group and others to
pursue ediblevaccines as tools for quashing autoim-munity. Although
oral delivery of anti-gens derived from infectious agents of-ten
stimulates the immune system, oraldelivery of “autoantigens”
(proteins de-
Edible Vaccines
As research into edible vaccines is progressing,so too are
efforts to make foodsmore nutritious.A much publicized
example,“golden rice,”takes aim at vita-min A deficiency, rampant
in many parts of Asia, Africa and Latin America. Thiscondition can
lead to blindness and to immune impairment,which contributes tothe
death of more than a million children each year.
Rice would be a convenient way to deliver the needed vitamin,
because thegrain is a daily staple for a third or more of all
people on the earth. But natural va-rieties do not supply vitamin
A. Golden rice, though, has been genetically alteredto make
beta-carotene,a pigment the body converts to vitamin A.
A team led by Ingo Potrykus of the Swiss Federal Institute of
Technology andPeter Beyer of the University of Freiburg in Germany
formally reported its creationthis past January in Science. In May
an agribusiness—Zeneca—bought the rightsand agreed to allow the
rice to be donated to facilities that will cross the beta-carotene
trait into rice species popular in impoverished areas and will
distributethe resulting products to farmers at no charge. (Zeneca
is hoping to make itsmoney from sales of the improved rice in
richer countries, where beta-carotene’santioxidant properties are
likely to have appeal.)
Golden rice is not yet ready to be commercialized, however. Much
testing stilllies ahead, including analyses of whether the human
body can efficiently absorbthe beta-carotene in the rice.Testing is
expected to last at least until 2003.
Meanwhile scientists are trying to enrichrice with still more
beta-carotene,with othervitamins and with minerals. At a
conferencelast year Potrykus announced success withiron; more than
two billion people world-wide are iron deficient.
Investigators are attempting to enhanceother foods as well. In
June, for instance, agroup of British and Japanese
investigatorsreported the creation of a tomato contain-ing a gene
able to supply three times theusual amount of beta-carotene.
Conven-tional breeding methods are being used,too, such as in an
international project fo-cused on increasing the vitamin and
miner-al content of rice and four other staples—wheat,corn,beans
and cassava.
Not everyone is thrilled by the recent ge-netic
coups.Genetically modified (GM) foodsin general remain
controversial.Some oppo-nents contend that malnutrition can be
com-bated right now in other ways—say, by con-
structing supply roads. And they fear that companies will tout
the benefits of thenew foods to deflect attention from worries over
other GM crops, most of which(such as plants designed to resist
damage from pesticides) offer fewer clear advan-tages for
consumers.High on the list of concerns are risk to the environment
and topeople.Supporters of the nutritionally improved foods
hope,however,that the ricewon’t be thrown out with the rinse water.
—Ricki Rusting, staff writer
“GOLDEN RICE” contains beta-
carotene, which adds color as well
as nutrition to the grain.
Moving against Malnutrition
70 Scientific American September 2000
COU
RTES
Y O
F PE
TER
BEYE
R U
nive
rsity
of F
reib
urg
Copyright 2000 Scientific American, Inc.
-
SUPPRESSIVESECRETIONS
SUPPRESSORT CELL
AUTO-ANTIGENDELIVEREDIN FOOD
M CELL
INTESTINALCAVITY
CYTOTOXICT CELL
NATURALKILLER
CELL
DESTRUCTIVESECRETIONS
STIMULATORYSECRETIONS
HELPERT CELL
B CELL
ANTIBODY
MACROPHAGE
DAMAGEDAREA
rived from uninfected tis-sue in a treated individ-ual) can
sometimes sup-press immune activity—aphenomenon seen fre-quently in
test animals. Noone fully understands thereasons for this
difference.
Some of the evidencethat ingesting autoanti-gens, or
“self-antigens,”might suppress autoimmu-nity comes from studiesof
type I diabetes, whichresults from autoimmunedestruction of the
insulin-producing cells (beta cells)of the pancreas. This
de-struction progresses si-lently for a time. Eventu-ally, though,
the loss ofbeta cells leads to a dras-tic shortage of insulin,
ahormone needed to helpcells take up sugar fromthe blood for
energy. Theloss results in high bloodsugar levels. Insulin
injec-tions help to control dia-betes, but they are by nomeans a
cure; diabeticsface an elevated risk of se-vere complications.
In the past 15 years, investigators haveidentified several beta
cell proteins thatcan elicit autoimmunity in people pre-disposed to
type I diabetes. The mainculprits, however, are insulin and a
pro-tein called GAD (glutamic acid decar-boxylase). Researchers
have also madeprogress in detecting when diabetes is“brewing.” The
next step, then, is to findways of stopping the underground
pro-cess before any symptoms arise.
To that end, my colleagues and I, aswell as other groups, have
developed
plant-based diabetes vaccines, such aspotatoes containing
insulin or GADlinked to the innocuous B subunit of theV. cholerae
toxin (to enhance uptake ofthe antigens by M cells). Feeding of
thevaccines to a mouse strain that becomesdiabetic helped to
suppress the immuneattack and to prevent or delay the onsetof high
blood sugar.
Transgenic plants cannot yet producethe amounts of self-antigens
that wouldbe needed for a viable vaccine againsthuman diabetes or
other autoimmune
diseases. But, as is true for infectious dis-eases,
investigators are exploring a num-ber of promising schemes to
overcomethat and other challenges.
Edible vaccines for combating au-toimmunity and infectious
diseases havea long way to go before they will beready for
large-scale testing in people.The technical obstacles, though, all
seemsurmountable. Nothing would be moresatisfying than to protect
the health ofmany millions of now defenseless chil-dren around the
globe.
Edible Vaccines Scientific American September 2000 71
The Author
WILLIAM H. R. LANGRIDGE, a leader in the ef-fort to develop
edible vaccines for infectious and au-toimmune diseases, is
professor in the department ofbiochemistry and at the Center for
Molecular Biolo-gy and Gene Therapy at the Loma Linda
UniversitySchool of Medicine. After receiving his Ph.D. in
bio-chemistry from the University of Massachusetts atAmherst in
1973, he conducted genetic research oninsect viruses and plants at
the Boyce Thompson In-stitute for Plant Research at Cornell
University. In1987 he moved to the Plant Biotechnology Center ofthe
University of Alberta in Edmonton, and hejoined Loma Linda in
1993.
Further Information
Oral Immunization with a Recombinant Bacterial Antigen Produced
inTransgenic Plants. Charles J. Arntzen in Science, Vol. 268, No.
5211, pages714–716; May 5, 1995.
Immunogenicity in Humans of a Recombinant Bacterial Antigen
Deliv-ered in a Transgenic Potato. C. O. Tacket et al. in Nature
Medicine, Vol. 4,No. 5, pages 607–609; May 1998.
A Plant-Based Cholera Toxin B Subunit-Insulin Fusion Protein
Protectsagainst the Development of Autoimmune Diabetes. Takeshi
Arakawa, JieYu, D. K. Chong, John Hough, Paul C. Engen and William
H. R. Langridge inNature Biotechnology, Vol. 16, No. 10, pages
934–938; October 1998.
Plant-Based Vaccines for Protection against Infectious and
Autoim-mune Diseases. James E. Carter and William H. R. Langridge
in Critical Re-views in Plant Sciences (in press).
SA
The autoimmune reaction responsible for type I diabetesarises
when the immune system mistakes proteins that aremade by pancreatic
beta cells (the insulin producers) for for-eign invaders.The
resulting attack, targeted to the offendingproteins, or
“autoantigens,” destroys the beta cells (below,left). Eating small
amounts of autoantigens quiets the pro-cess in diabetic mice, for
unclear reasons. The autoantigensmight act in part by switching on
“suppressor” cells of theimmune system (inset), which then block
the destructive ac-tivities of their cousins (below, right).
STOPPING AUTOIMMUNITY
AFTER TREATMENT
Activated suppressor cellsgo to pancreas
PRESERVEDBETA CELL
AUTOANTIGEN
BETA CELL UNDER ATTACK
IN PANCREAS
BEFORE TREATMENT
JARE
D S
CH
NEI
DM
AN
DES
IGN
The
view
s,op
inio
ns a
nd/o
r find
ings
con
tain
ed in
this
repo
rt a
re th
ose
of th
e au
thor
and
sho
uld
not b
e co
nstr
ued
as a
po
sitio
n,po
licy,
deci
sion
or e
ndor
sem
ent o
f the
fede
ral g
over
nmen
t or o
f the
Nat
iona
l Med
ical
Tec
hnol
ogy
Test
bed,
Inc.
Copyright 2000 Scientific American, Inc.