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[EFFECTS ON SATELLITES]                                                                                           High-energy particles degrade solar panels.
                                                                                                                                                                                                                                                                                                   They also penetrate circuitry and generate
                                                                                                                                                                              Feeling the Full Brunt                                                                                                 spurious signals that can corrupt
                                                                                                                                                                                                                                                                                                       data or even cause a satellite to
                                                                                                                                                                              The harshness of space takes a toll on satellites even                                                                    spiral out of control.
Impact of a Coronal Mass Ejection                                                                             The 1859 Superstorm                                             at the best of times. A superstorm would cause years’
                                                                                                                                                                              worth of damage within a few hours.
NORMAL CONDITIONS: Earth’s magnetic field typically deflects the charged particles streaming                    The authors have reconstructed what happened in
out from the sun, carving out a teardrop-shaped volume known as the magnetosphere. On the sun-                1859, based in part on similar (though less intense)                                                                                                                                                                                                 How to
facing side, the boundary, or magnetopause, is about 60,000 kilometers from our planet. The field              events seen by modern satellites. UTC is Coordinated
                                                                                                              Universal Time — basically, Greenwich Mean Time.
                                                                                                                                                                                                                                                                                                                                                                   Prepare
also traps particles in a doughnut-shaped region known as the Van Allen belts.                                                                                                                                                                                                                                                                                     If a storm were on its way,
                                                                                                                              August 26                                                                                                                                                                                                                            we could do the following:
                                              Magnetopause
                                                                                                                    Large sunspot group
                                                                                                                  appears near longitude                                                                                                                                                                                                                             Satellite operators put
                                                                                         Magnetic field line   55 degrees west on the sun;                                                                                                                                                                                                                            off critical command
                                                       Earth
                                                                                                              first CME possibly launched.                                                                                                                                                                                                                            sequences. During the
                                                                                                                                                                                                                                                                                                                                                                     storm itself, they
                                                                                                                              August 28
                                                                                                                                                                                                                                                                                                                                                                     monitor their birds and
  Sun                                                              Van Allen belts                            CME arrives at Earth with a
                                                                                                                                                                                                                                                                                                                                                                     override any spurious
                                                                                                                glancing blow because of
                                                                                                                                                                                                                                                                                                                                                                     commands.
                                                                                                                 the solar longitude of its
                  Solar wind
                                                                                                               source; its magnetic orien-      SUNSPOTS
                                                                                                                                                                                                                                                                                                                                                                     GPS users switch to
                                                                                                                      tation is northward.
                                                                                      Magnetosphere                                                                                                                                                                                                                                                                  backup navigation
                                                                                                                 August 28 07:30 UTC                                                                                                                                                                                                                                 systems.
                                                                                                              Greenwich Magnetic Obser-                                       Solar particles and radiation puff up the
                                                                                                                   vatory detects a distur-                                   atmosphere, increasing the drag forces                                                                                                                                                 Astronauts avoid
                                                                                                                bance, signaling compres-                                     on low-orbiting satellites.                                                                                                                                                            space walks.
FIRST STAGES OF IMPACT: When the sun fires off a coronal mass ejection (CME), this bubble of
                                                                                                                                                                                                                                                                                  Electrons can collect on
ionized gas greatly compresses the magnetosphere. In extreme cases such as superstorms, it can                sion of the magnetosphere.
                                                                                                                                                                                                                                                                                satellites and cause static
push the magnetopause into the Van Allen belts and wipe them out.                                                                                                                                                                                                               electrical discharges that
                                                                                                                 August 28 22:55 UTC                                                                                                                                               physically damage the
                                                                                                                  Main storm phase begins,                                                                                                                                  circuitry (                   ).
                                                                                                                with large magnetic distur-
                                                                                                                bances, telegraphic disrup-     CORONAL MASS EJECTION
                                                                                                                tions and auroral sightings
                                                                                                               as far south as magnetic lat-                                                                                                                        w w w. S c i A m . c o m
                                                                                                                    itude 25 degrees north.
   Sunspots       Coronal mass ejection                                                                                       August 30
                                                                                                                                                                                                                             [EFFECTS ON POWER]
                                                                                                               Geomagnetic disturbances
                                                                                                                    from first CME end.                                                                                       Darkness Falls
                                                                                                              September 1 11:15 UTC                                                                                          Electric currents in the ionosphere induce electric currents in the ground and in pipelines.
                  CME magnetic field (S)                                                                             Astronomer Richard C.
                                                                                 Earth’s magnetic field (N)
                                                                                                                Carrington, among others,
                                                                                                              sights a white-light flare on
                                                                                                                                                AURORA SIGHTINGS
                                                                                                                the sun; the large sunspot                                                                                                                                                                           Electric currents
MAGNETIC RECONNECTION: The solar gas has its own magnetic field, and as it streams past our                      group has rotated to longi-                                                                                                                                                                          in the ionosphere
planet, it stirs up turbulence in Earth’s magnetic field. If this field points in the opposite direction as            tude 12 degrees west.
Earth’s, the two can link up, or reconnect—releasing magnetic energy that accelerates particles
                                                                                                              September 2 05:00 UTC
and thereby creates bright auroras and powerful electric currents.
                                                                                                              Greenwich and Kew magnet-
                                                                                                                 ic observatories detect dis-
                    Turbulent field lines
                                                                                                               turbances followed immedi-
                                                                         CME plasma                           ately by geomagnetic chaos;
                                                                                                              second CME arrives at Earth                                                                           Transformer
                                                                                                               within 17.5 hours, traveling                                                                                                                                                       Induced
                                                                                                                at 2,380 kilometers per sec-                                                                                                                                                      current
                                                                                                                                                X-RAY FLARE
                                                                                  Reconnected                     ond with southward mag-
                                         Auroras                                     region                       netic orientation; auroras
    Reconnected
       region                                                  Current                                            appear down to magnetic
                                                                                                                  latitude 18 degrees north.

                                                                                                                        September 3–4
                                                                                                                                                                                                                                                                                                                                         Pipeline
                                                                                                              Main phase of geomagnetic
                                                                                                               disturbances from second
                                                                                                               CME ends; scattered auro-
                                                                                                               ral sightings continue, but
                                                                                                                                                                     CREDIT




                                                                                                               with diminishing intensity.                                                                                                                                         These currents surge                                                                      The entire East Coast and much of the rest of the country would
                                                                                                                                                                                                                                                                                  into transformers and                                                                      lose power. This map shows the blacked-out regions expected
                                                                                                                                                AURORA SIGHTINGS                                                                                                                                                                                    Induced                  from a severe storm like that of 1921, which would induce ground
                                                                                                                                                                                                                                                                                can fry them. It would
82 S C I E N T I F I C A M E R I C A N                                                                                                          August 2008                                                                                                                    take weeks or longer for                                              current                 fields of about 20 volts per kilometer. Scientists have yet to model
                                                                                                                                                                                                                                                                              workers to fix them all.                                                                        the effects of a full-blown 1859-like storm on the power grid.



                                                                                                                                                                                                                          rent (DC). The DC flows up the transformer                      could bring down the entire grid. Other indus-                                               that improves the accuracy of GPS position esti-
                                                                                                                                                                                                                          ground wires and can lead to temperature spikes                trial countries are also vulnerable, but North                                               mates. Commercial aircraft had to resort to in-
                                                                                                                                                                                                                          of 200 degrees Celsius or higher in the trans-                 America faces greater danger because of its prox-                                            flight backup systems.
                                                                                                                                                                                                                          former windings causing coolant to vaporize                    imity to the north magnetic pole Because of the                                                 High-energy particles will interfere with air-




                                                                                                                                                                                                                                                                                                                                                               )
[SLICING SPACETIME]

      How Time Is Not Like Space
      Physicists, artists and graph makers of all kinds routinely depict time as another dimension of space, creating a unified spacetime — shown here as a three-
      dimensional block in which a ball bounces off a wall. Relativity theory holds that spacetime can be sliced up in various ways. But not all are equally sensible.
               t

                                                                     The usual way takes slices of space at successive moments of time, creating a movie of the ball’s
                                                                     motion. Each frame leads to the next, according to the familiar laws of physics.
                                                                                                                 y



                                                                 ●
                                                                 4
                                                                 ●
                                                                 3
                                                                 ●
                                                                 2


                                                                 ●
                                                                 1
                                                                                            x
                                                                                                      ●
                                                                                                      1                    ●
                                                                                                                           2                   ●
                                                                                                                                               3                    ●
                                                                                                                                                                    4


                                                                     An alternative considers slices not from past to future but from left to right. Each slice is part
                                                                     space, part time. To the left of the wall, the ball appears in two positions; on the right, it does not
                                                                     appear at all. If this slicing seems strange, it should: it makes the laws of physics very unwieldy.
                                                                                            t

                                                             y




                                                                                                                 x
x                                                                       ●
                                                                        1       ●●●
                                                                                2 34                  ●
                                                                                                      1                    ●
                                                                                                                           2                   ●
                                                                                                                                               3                    ●
                                                                                                                                                                    4




    [A NEW VIEW OF TIME]

    Who Needs Time, Anyway?                                                                                                                    1 beat

    Time is a way to describe the pace of
    motion or change, such as the speed
    of a light wave, how fast a heart beats,
    or how frequently a planet spins ...

                                                                                                            ... but these processes could
                   LIGHT:                                                                                   be related directly to one
                   300,000 kilometers per second                                                            another without making
                                                                                                            reference to time.


                   HEART:
                   75 beats per minute

                                               VS.
                                                                                                                                            240,000 kilometers per beat
                   EARTH:
                   1 rotation per day
                                                                                                108,000 beats
                                                                                                per rotation



    Thus, some physicists argue that time is a common currency, making the world easier to describe
                                                                                                                                             1 cup of coffee
    but having no independent existence. Measuring processes in terms of time could be like using
    money (    ) rather than barter transactions (   ) to buy things.
                                                                                        50 cups of coffee
                                                                                        per pair of shoes

                                                                            VS.                                                                                    1,000 cups
                                                                                                                                                                   of coffee
                                                                                                                                                                   per used car

          $2                $100                   $2,000



          [see “A Quantum Threat to Special Relativity,”              recently investigated timeless theories [see “A
          by David Z. Albert and Rivka Galchen; S����-                Simple Twist of Fate,” by George Musser, on
          ����� A�������, March 2009].                                page 14]. But to convey the basic problem that
mundane activity. The great strength of multi-
                                                                                                                                            touch is letting multiple people work together on
                                                                                                                                            a complex activity. It is hard to remember how
                                                                                                              LED                           liberating the mouse seemed when it freed peo-
                                                                                                                                            ple from keyboard arrow keys some 25 years
[HOW IT WORKS]
                                                                                                                                            ago. Soon the multi-touch interface could help
                                                                                                                                            untether us from the ubiquitous mouse. “It’s
Tracking Fingers                                                         Pressure-sensitive
                                                                                   polymer
                                                                                                                    Internal reflections
                                                                                                                                            very rare that you come upon a really new user
The most advanced multi-touch                                                                                                               interface,” Han says. “We’re just at the begin-
                                                                                                                                Light       ning of this whole thing.”
screens respond to the motion and                            Reflection                                                          scattered
pressure of numerous fingers. In the                          sensor                                                             toward
                                                                                                                                reflection     [INSIDE LOOK]
Perceptive Pixel design (           ),                                                                                          sensor
projectors send images through an
acrylic screen onto the surface facing
the viewer. When fingers or other
                                                                                                                                              Touch Table
                                                                                                                    Acrylic waveguide
objects (such as a stylus) touch the                                                                                                          A projector inside Microsoft’s
                                                       Projector
surface, infrared light shone inside the                                                                                                      multi-touch table, called                             Infrared cameras
                                                                               Image from
acrylic sheet by LEDs scatters off the                                           projector                                                    Surface, sends imagery up
fingers and back to sensors. Software                                                                                                          through the acrylic top. An
interprets the data as finger move-                                                                                                            LED shines near-infrared light
                                           LED                                                                                                up as well, which reflects off
ments. Tapping the screen brings up                                        To create a signal, LEDs bounce light through the acrylic
command menus when desired.                                                                                                                   objects or fingers back to var-
                                                                           sheet. No light escapes. But if a finger is placed against the      ious infrared cameras; a com-          Computer
                                                                           face (      ), light will scatter off it toward the sensors.       puter monitors the reflections
                                                                           Also, a pressure-sensitive coating flexes when pressed              to track finger motions.
                                                 Computer                  firmly or lightly, making the scattered fingertip signal
                                                                           appear slightly brighter or dimmer, which the computer                                                       Projector
                                                                           interprets as more or less pressure.                                                                                                        LED light
                                                                                                                                                                                                                       source
Ventromedial
       prefrontal cortex        Nucleus accumbens

      ex-
                                                                                      Subthalamic nucleus      Mediodorsal thalamus
     bbs
                                                                                                                                          Motor thalamus
      ba-                                                          Globus pallidus
    um-                                                          internal segment
    tine
     ver,
   Ani-
      the                                                      Anterior
     rive                                              cingulate cortex
   mak-
   ckly
   mar-
    iven                   Amygdala                  Anterior limb
    es—                                             of the internal
    ion,                   Ventral tegmental area          capsule
     gic.
             BRAIN AREAS that become
    gni-
   n be
             activated in response to                 Subgenual
   n of
             reward or risk include those              cingulate
             shown above, among others.
   nan-
                                                              Nucleus
                                                           accumbens



                                                                   Orbitofrontal
 HOW                                                                     cortex

                                                                                      Ventral       Lateral
                                                                                     pallidum hypothalamus                                                 Brain stem
                                                                                                                   Thalamus
WHERE
                                                                                                      Sensory thalamus
                       WHAT                                                                                                        Pedunculopontine nucleus
                                                                                                              Periventricular gray/periaqueductal gray
[AFFECTED NATIONS]

                                                                                                                                                            WORLDWIDE RESISTANCE
                                                                                                                                                            Tuberculosis occurs in virtually every country in the world, although it is most wide-
                                                                                                                                                            spread in developing nations. The incidence of TB caused by strains of        resistant to
                                                                                                                                                            two or more of the first-line drugs for the disease — so-called multidrug-resistant TB
                                                                                                                                                            (MDR-TB) — has been rising as a result of improper use of antibiotics. Worse still is exten-
                                                                                                                                                            sively drug-resistant TB (XDR-TB) — a largely untreatable form identified in 2006; as of
                                                                                                                                                            June 2008, 49 countries had confirmed cases. Sadly, that figure most likely underesti-
[INFECTION BASICS]
                                                                                                                                                            mates XDR-TB’s prevalence.
AN ILL WIND                                                                                                                                                 TB
Brain           Tuberculosis, caused by the bacterium      , occurs in both latent and active forms. People can become infected by breathing
                in even just a few    bacteria released into the air when those with active TB cough, spit or talk.    causes coughing, the
                most familiar symptom, because it accumulates abundantly in the lungs, but it can harm other organs as well (          ).


                                                                                                                                                            Reported cases of
             Lung                                                                               tends to concentrate in the air sacs, or alveoli, of the    tuberculosis per
                                                                                            lungs because it prefers environments rich in oxygen. In        100,000 citizens
                                                                                                                                                                     it
                                                                                                                                                                     it
                                                                   Macrophage                 most people, the immune system is able to keep bacterial
                                                                                                                                                                 No estimate
                                                                                                replication in check, dispatching defensive cells known
                                                                                                  as macrophages to the site of infection, where they            0–24
                                                                                                   form a shell around the bacteria. But in 10 percent of        2
                                                                                                                                                                 25–49
                                                       Alveolus                                     infected individuals,      breaks down the shell,
                                                                                                     after which it can begin to multiply.                       50–99
                                                                                                                                                                 100–299
                                                                                                                                                                 300 or more
                                                                            Mtb

              Kidney                                                                                                                                        Multidrug-resistant TB
                                                                                                          Scan highlights      infection in lung.
 Bone




                            Unfettered by the immune system, the bacteria destroy the tissue of
                         the lungs; some may also make their way into the bloodstream and infect                                                            Percent of MDR-TB
                                                                                                                                                                     f
                         other parts of the body, including the brain, kidneys and bone. Eventually                                                         among new TB cases
                         affected organs may sustain so much damage they cease to function, and                                                             1994-2007
                         the host dies.                                                                                                                          More than 6%
                                                                                                                                                                 3
                                                                                                                                                                 3%–6%
                                                                                                                                                                 Less than 3%
                              the problem is that bacteria are autonomous                       some of those proteins might be worth consid-
                                                                                                                                                                 No data
                              life-forms, selected throughout evolution for                     ering as drug targets. Analysis of the TB genome
                              their ability to adapt and respond to external                    also hinted that, contrary to conventional wis-
                              threats. Like modern aircraft, they have all                      dom, the bacterium is perfectly capable of living           Extensively drug-resistant TB
                              manner of redundancies, bypasses, fail-safes                      in the absence of air— a suggestion now verified.
                              and emergency backup systems. As Jeff Gold-                       Under such anaerobic conditions, Mtb’s metab-
                              blum’s character in Jurassic Park puts it, life                   olism slows down, making it intrinsically less
                              finds a way. Until we truly appreciate the com-                   sensitive to existing antibiotics. Targeting the
                              plexities of how TB interacts with humans, new                    metabolic elements that remain active under
                              drugs against it will remain elusive. The good                    these circumstances is one of the most promis-
                                     i h               ki                  h                    i          i f     h       i              i
[STAGES TO WATCH]

        From Animal Microbe to Human Pathogen
        The process by which a pathogen of animals evolves into one exclusive to humans occurs in five stages. Agents can become stuck in
        any of these stages. Those in early stages may be very deadly (Ebola, for example), but they claim few lives overall because they cannot
        spread freely among humans. The better able a virus is to propagate in humans, the more likely it is to become a pandemic.                                                                      [PREVENTION PROPOSAL]


        DISEASE EXAMPLES:      Reichenowi malaria         Rabies                Ebola         Dengue              HIV
                                                                                                                                                                                                        Building a Surveillance Network
                                                                                                                                                                                                        By monitoring microorganisms in wild animals and the people who are frequently exposed
                                                                                                                                                                                                        to them, scientists may be able spot an emerging infectious disease before it becomes
                                                                                                                                                                                                        widespread. To that end, the author recently organized the Global Viral Forecasting Initia-
                                                                                                                                                                                                        tive (GVFI), a network of 100 scientists and public health officials in six countries (    and
                                                                                                                                                                                                                     ) who are working to track potentially dangerous agents as they move from
Stage 1: Pathogen is present in                                                                                                                                                                         animals into human populations. The GVFI focuses on tropical regions (           ) in particu-
animals but has not been detected                                                                                                                                                                       lar, because they are home to a wide variety of animal species and because humans there
in humans under natural conditions.                                                                                                                                                                     commonly come into contact with them through hunting and other activities. Eventually
                                                                                                                                                                                                        the GVFI hopes to expand the network to include more countries with high levels of biodi-
          Stage 2: Animal pathogen has been trans-                                                                                                 COUNTRY: Cameroon                                    versity, some of which are shown here (              ).
                                                                                                                                                   VIRUSES PREVIOUSLY SPAWNED: HIV                                                                                                                       COUNTRY: China
          mitted to humans but not between humans.                                                                                                 SENTINEL POPULATION UNDER STUDY FOR NEW PATHOGENS:                                                                                                    VIRUSES PREVIOUSLY SPAWNED: SARS, H5N1
                                                                                                                                                   People who hunt and butcher wild animals                                                                                                              SENTINEL POPULATION : “Wet market” workers



                        Stage 3: Animal pathogen that can be trans-
                        mitted between humans causes an outbreak of
                        disease but only for a short period before dying out.



                                       Stage 4: Pathogen exists in animals and undergoes a regular
                                       cycle of animal-to-human transmission but also sustains long
                                       outbreaks arising from human-to-human transmission.




        SOURCE:
                                                                                        Stage 5: Pathogen has become exclusive to humans.          COUNTRY: Democratic Republic   of the Congo
                          Nature,                                                                                                                  VIRUSES PREVIOUSLY SPAWNED:                                         Primary study site (human and animal testing)   Tentative site for future study
                                                                                                                                                   Marburg, monkeypox, Ebola                                           Secondary study site (animal testing only)      Tropical region                   COUNTRY: Malaysia
                                                                                                                                                   SENTINEL POPULATION :                                                                                                                                 VIRUSES PREVIOUSLY SPAWNED: Nipah
                                                                                                                                                   People who hunt and butcher wild animals                                                                                                              SENTINEL POPULATION : Wildlife hunters
[WHAT ASTRONOMERS LOOK FOR]

Glowing in the Dark
                                                                           Infrared Light Reveals Disks and Thus Planets or Their Building Blocks
A     stronomers generally detect planets indirectly, by virtue
      of their effects on the velocity, position or brightness
of their host stars. For most of the cases discussed in the
                                                                           A circumstellar disk of dust and gas, like the one that gave rise to the planets of our solar system, absorbs
                                                                           starlight and emits infrared radiation. We observe a composite of direct starlight and disk emission.
article, astronomers focus on one type of indirect sign:
the presence of a disk of dust orbiting the star. A so-called
protoplanetary disk occurs around newly born stars and is
thought to be the site of planet formation. A so-called debris                                                         Starlight
disk occurs around mature stars and is thought to arise from
collisions or evaporation of comets and asteroids, thus
                                                                                                                                                                                                 Circumstellar disk
signaling the likely presence of planets now or in the past.
    Observers identify both types of disk from how they
absorb starlight and reradiate the absorbed energy at infra-                                                                                                                                                               Light from disk
                                                                                                                                   Star
red wavelengths (         ). NASA’s Spitzer Space Telescope,
launched in 2003, has proved to be a veritable disk discovery
machine. Its large field-of-view infrared cameras can cap-
ture hundreds of stars in a single image and pinpoint those
with evidence of disks for further study.
    Spitzer builds on the successes of past infrared telescopes,
such as the Infrared Astronomical Satellite (IRAS) mission in
the 1980s and the European Space Agency’s Infrared Space                                                                                                                                                                  Brown dwarf plus disk
                                                                                                                                                                                                                          Brown dwarf
Observatory (ISO) in the mid-1990s. Unlike IRAS, which was                                                                                                                                                                Disk
an all-sky survey, Spitzer points at specific celestial bodies for
intensive study, and the five-year-plus lifetime of its liquid-                                                  An example is the brown dwarf OTS 44,




                                                                                                                                                                  Brightness (arbitrary units)
helium coolant far exceeds that of any previous mission. The                                                      whose spectrum (                 ) initially
telescope has studied everything from extrasolar planets to                                                         falls off at infrared wavelengths but
                                                                                                               then flattens — indicating that the dwarf,
galaxies in the early universe.                                                                           whose spectrum would be expected to peak at
    The coolant is now running out, and the telescope will                                                 short wavelengths (          ), is surrounded by
soon start to warm from nearly absolute zero to 30 kelvins.                                                      cooler material whose spectrum peaks
Even so, it will be able to operate at the short-wavelength                                                                  at longer wavelengths (         ).
end of the infrared band through at least the middle of 2011.        Even when the system is
Taking up the slack will be the newly launched Herschel              too far away for telescopes
Space Observatory and the James Webb Space Telescope                 to resolve spatially, the spectrum                                                                                          1               3             10             30
(JWST), planned for launch in 2013. —                                reveals the blending of light.                                                                                                        Wavelength (microns)
[BASICS]

Vaccines Mimic Infection to Avert It                                                                                                                                   IMMUNE MEMORY
                                                                                                                                                                       Some of the B and T cells become long-lived memory
Vaccines deliver a killed or weakened pathogen, or pieces of it, to trigger an immune response that generates “memory” cells primed to
                                                                                                                                                                       cells, standing guard against a future infection.
recognize the same microorganism quickly in the future. These cells can later block true infections or at least minimize illness.

                                                                                                                                      Killer T cells
                                                              Cytokines
                                                                                                                                                                                                                                                                                                     innat
                                                                                                                                                                      Attempted infection                Memory T cells and B cells
                                                                                                                                                                                                                                                               COMMON                                ling f
                                                              Virus fragments
                                                              V                                                                                                                                                                                                VACCINE TYPES                         ropha
                                      Dendritic cell
                                                                                                                                                                                                                                                               ■   ATTENUATED: Live                     des
                  Injection                                                                                                                                                                                                                                        but weakened whole                     c
                     site
                                                                                                                                                                                                                                                                   virus or bacterium.
                                                                                                        T cell precursors                                                            Infected cell                                                                 Minimal reproduc-
       Virus in                                                                                                                       Helper T cells
                                                                                                                                                                                                                                                                   tion extends
       vaccine
                                                                                                                                                                                                                                                                   immune cells’
                                                                                                                                                                                                                                                                   exposure to antigen                      t
                                                        Maturation                                                                                                                                                                                                 without causing disease.               can
                                                        and migration
                  Infected cells                          to lymph nodes                                                                                                                                                                                                                                   pe
                                                                                                                                                                                                                                                               ■   INACTIVATED:
                                                                                                        Cytokines                                                                                                                                                  Whole but “killed”
                                                                                                                                                         Antibodies                                                                                                and unable to
                                                                                                                            B cell                                          remain in the body as “memory” cells — some-                                           reproduce or to
                                                         Lymph node                                                                                                         times for decades — ready to squelch any at-                                           cause disease.
                                   Macrophage                                                   Antigen                                                                     tempted reinfection by the same organism. Vac-                                                                                 ad
                                                                                                                                                                            cines replicate this process by introducing a                                      ■   SUBUNIT: Fragments                    the
                                                                                                                                                                            whole pathogen or fragments of it that will be                                         of the pathogen, such                    k
     VACCINE ADMINISTRATION                                                     DENDRITIC CELL MIGRATION AND INTERACTIONS                                                                                                                                          as genetic material
     A small dose of live but weakened virus is one common form of              Loaded with foreign material (antigen), dendritic cells mature and migrate                  recognized as a foreign invader. Not all vaccines
                                                                                                                                                                                                                                                                   or external pro-
     vaccine. Injected into the skin, the virus will infect some cells          to lymph nodes to interact with T cells and B cells, components of the                      succeed in generating a full immune response,
     and reproduce slowly. “Innate” immune system cells, such as                “adaptive” immune system. Displaying antigen and emitting cytokines,                                                                                                               teins, provide
     macrophages and dendritic cells, engulf and digest foreign                 the dendritic cells induce T cells to mature into helper and killer types; the              but some pathogens can be stopped by antibod-                                          antigen for immune
     material and infected body cells. Dendritic cells also emit                helper T cells also signal to incite the killer T cells to attack infected cells            ies alone, so killer T cells are not needed for                                        cells to recognize.                      l
     signaling chemicals called cytokines to sound an alarm.                    and induce B cells to produce antibodies tailored to the pathogen.                          protection.
                                                                                                                                                                                The nature of the pathogen and how it causes
                                                                                                                                                                            ill                      i d i       ’      id




                                                                                                                 [VACCINE BOOSTERS]


                                                                                                                 Adjuvants                                                       PATHOGEN RECOGNITION                                                                                              TLR          NATURAL TRIGGER

                                                                                                                 Add Emphasis
                                                                                                                                                                                 Dendritic cells contain Toll-like receptors (TLR) that each recognize                                             ●● ●
                                                                                                                                                                                                                                                                                                   1 2 6        Bacterial lipoproteins
                                                                                                                                                                                 molecules typical of many pathogens, such as bacterial proteins or                                                ●
                                                                                                                                                                                                                                                                                                   3            Double-stranded RNA
                                                                                                                                                                                 distinctive viral gene motifs (           ). Adjuvants that trigger                                                            Lipopolysaccharide (LPS),
                                                                                                                                                                                 one or a combination of TLRs can simulate different natural threats.
                                                                                                                                                                                                                                                                                                   ●
                                                                                                                                                                                                                                                                                                   4
                                                                                                                 Adjuvants enhance immune responses to vaccine                                                                                                                                                  heat-shock proteins,
                                                                                                                 antigens by several mechanisms, but their most                                                                                                                   Killer T cells                respiratory syncytial virus
                                                                                                                                                                                                                                                                                                   ●5           Bacterial flagellin protein
                                                                                                                 potent effects are likely to be through activation
                                                                                                                                                                                                                                                                        IL-12                      ●●
                                                                                                                                                                                                                                                                                                    7 8         Single-stranded RNA
                                                                                                                 of microbe-recognition receptors on dendritic                                                                                                                                                  Bacterial CpG DNA
                                                                                                                                                                                                                                       Cytokines
                                                                                                                                                                                                                                                                                                   ●9
                                                                                                                 cells. Depending on the type of threat they sense,                                                                                                                                ●
                                                                                                                                                                                                                                                                                                   10           Unknown
                                                                                                                 dendritic cells will direct other immune cells to                                                                                                                                 ●
                                                                                                                                                                                                                                                                                                   11           Bacterial profilin protein
                                                                                                                 respond in different ways. Vaccine designers                                                                                                                    Helper T cells
                                                                                                                                                                                 Toll-like receptor
                                                                                                                 can use this knowledge to choose adjuvants that
                                                                                                                 will not only boost immune response but also                                                                                                           IL-12                      DENDRITIC CELL DIRECTIONS
                                                                                                                                                                                                                                                                                                   Dendritic cells’ signaling determines
                                                                                                                 emphasize the desired responses.
                                                                                                                                                                                                                                                                                                   how T and B cells will mature and
                                                                                                                                                                                                                                                                                                   proliferate. For example, the cytokine
                                                                                                                                                                                                                                                             Antibody-inducing helper T cells      interleukin-12 favors development of
                                                                                                                                                                                                                                                                                                   killer T cells and a helper T subtype
                                                                                                              lar keys, a group known as the Toll-like recep-                                                                                                                                      needed to defend against intracellular
                                                                                                                                                                                                                                                                        IL-6
                                                                                                              tors (TLRs) seemed most important for driving                                                                                                                                        pathogens, whereas IL-6 favors a
                                                                                                              the dendritic cells’ behavior [see “Immunity’s                                                                                                                                       helper T type that induces B cells to
                                                                                                                                                                                                                                                                                                   produce antibodies. IL-6, together
                                                                                                              Early-Warning System,” by Luke A. J. O’Neill;                                                                                              Inflammation-inducing helper T cells      with IL-23, induces still another helper
                                                                                                              S��������� A�������, January 2005].                                                                                                                                                  T subtype that promotes inflamma-
                                                                                                                                                                                                                                                                         IL-6
                                                                                                                                                                                                                                                                                                   tion. Interleukins themselves are also
                                                                                                                 To date, 10 functional Toll-like receptors                                                                                                                                        under study as adjuvants.
                                                                                                              have been identified, and each recognizes a dif-                                                                                                           IL-23
                                                                                                              ferent basic motif of viruses or bacteria. TLR-4
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Infographics

  • 1. [EFFECTS ON SATELLITES] High-energy particles degrade solar panels. They also penetrate circuitry and generate Feeling the Full Brunt spurious signals that can corrupt data or even cause a satellite to The harshness of space takes a toll on satellites even spiral out of control. Impact of a Coronal Mass Ejection The 1859 Superstorm at the best of times. A superstorm would cause years’ worth of damage within a few hours. NORMAL CONDITIONS: Earth’s magnetic field typically deflects the charged particles streaming The authors have reconstructed what happened in out from the sun, carving out a teardrop-shaped volume known as the magnetosphere. On the sun- 1859, based in part on similar (though less intense) How to facing side, the boundary, or magnetopause, is about 60,000 kilometers from our planet. The field events seen by modern satellites. UTC is Coordinated Universal Time — basically, Greenwich Mean Time. Prepare also traps particles in a doughnut-shaped region known as the Van Allen belts. If a storm were on its way, August 26 we could do the following: Magnetopause Large sunspot group appears near longitude Satellite operators put Magnetic field line 55 degrees west on the sun; off critical command Earth first CME possibly launched. sequences. During the storm itself, they August 28 monitor their birds and Sun Van Allen belts CME arrives at Earth with a override any spurious glancing blow because of commands. the solar longitude of its Solar wind source; its magnetic orien- SUNSPOTS GPS users switch to tation is northward. Magnetosphere backup navigation August 28 07:30 UTC systems. Greenwich Magnetic Obser- Solar particles and radiation puff up the vatory detects a distur- atmosphere, increasing the drag forces Astronauts avoid bance, signaling compres- on low-orbiting satellites. space walks. FIRST STAGES OF IMPACT: When the sun fires off a coronal mass ejection (CME), this bubble of Electrons can collect on ionized gas greatly compresses the magnetosphere. In extreme cases such as superstorms, it can sion of the magnetosphere. satellites and cause static push the magnetopause into the Van Allen belts and wipe them out. electrical discharges that August 28 22:55 UTC physically damage the Main storm phase begins, circuitry ( ). with large magnetic distur- bances, telegraphic disrup- CORONAL MASS EJECTION tions and auroral sightings as far south as magnetic lat- w w w. S c i A m . c o m itude 25 degrees north. Sunspots Coronal mass ejection August 30 [EFFECTS ON POWER] Geomagnetic disturbances from first CME end. Darkness Falls September 1 11:15 UTC Electric currents in the ionosphere induce electric currents in the ground and in pipelines. CME magnetic field (S) Astronomer Richard C. Earth’s magnetic field (N) Carrington, among others, sights a white-light flare on AURORA SIGHTINGS the sun; the large sunspot Electric currents MAGNETIC RECONNECTION: The solar gas has its own magnetic field, and as it streams past our group has rotated to longi- in the ionosphere planet, it stirs up turbulence in Earth’s magnetic field. If this field points in the opposite direction as tude 12 degrees west. Earth’s, the two can link up, or reconnect—releasing magnetic energy that accelerates particles September 2 05:00 UTC and thereby creates bright auroras and powerful electric currents. Greenwich and Kew magnet- ic observatories detect dis- Turbulent field lines turbances followed immedi- CME plasma ately by geomagnetic chaos; second CME arrives at Earth Transformer within 17.5 hours, traveling Induced at 2,380 kilometers per sec- current X-RAY FLARE Reconnected ond with southward mag- Auroras region netic orientation; auroras Reconnected region Current appear down to magnetic latitude 18 degrees north. September 3–4 Pipeline Main phase of geomagnetic disturbances from second CME ends; scattered auro- ral sightings continue, but CREDIT with diminishing intensity. These currents surge The entire East Coast and much of the rest of the country would into transformers and lose power. This map shows the blacked-out regions expected AURORA SIGHTINGS Induced from a severe storm like that of 1921, which would induce ground can fry them. It would 82 S C I E N T I F I C A M E R I C A N August 2008 take weeks or longer for current fields of about 20 volts per kilometer. Scientists have yet to model workers to fix them all. the effects of a full-blown 1859-like storm on the power grid. rent (DC). The DC flows up the transformer could bring down the entire grid. Other indus- that improves the accuracy of GPS position esti- ground wires and can lead to temperature spikes trial countries are also vulnerable, but North mates. Commercial aircraft had to resort to in- of 200 degrees Celsius or higher in the trans- America faces greater danger because of its prox- flight backup systems. former windings causing coolant to vaporize imity to the north magnetic pole Because of the High-energy particles will interfere with air- )
  • 2. [SLICING SPACETIME] How Time Is Not Like Space Physicists, artists and graph makers of all kinds routinely depict time as another dimension of space, creating a unified spacetime — shown here as a three- dimensional block in which a ball bounces off a wall. Relativity theory holds that spacetime can be sliced up in various ways. But not all are equally sensible. t The usual way takes slices of space at successive moments of time, creating a movie of the ball’s motion. Each frame leads to the next, according to the familiar laws of physics. y ● 4 ● 3 ● 2 ● 1 x ● 1 ● 2 ● 3 ● 4 An alternative considers slices not from past to future but from left to right. Each slice is part space, part time. To the left of the wall, the ball appears in two positions; on the right, it does not appear at all. If this slicing seems strange, it should: it makes the laws of physics very unwieldy. t y x x ● 1 ●●● 2 34 ● 1 ● 2 ● 3 ● 4 [A NEW VIEW OF TIME] Who Needs Time, Anyway? 1 beat Time is a way to describe the pace of motion or change, such as the speed of a light wave, how fast a heart beats, or how frequently a planet spins ... ... but these processes could LIGHT: be related directly to one 300,000 kilometers per second another without making reference to time. HEART: 75 beats per minute VS. 240,000 kilometers per beat EARTH: 1 rotation per day 108,000 beats per rotation Thus, some physicists argue that time is a common currency, making the world easier to describe 1 cup of coffee but having no independent existence. Measuring processes in terms of time could be like using money ( ) rather than barter transactions ( ) to buy things. 50 cups of coffee per pair of shoes VS. 1,000 cups of coffee per used car $2 $100 $2,000 [see “A Quantum Threat to Special Relativity,” recently investigated timeless theories [see “A by David Z. Albert and Rivka Galchen; S����- Simple Twist of Fate,” by George Musser, on ����� A�������, March 2009]. page 14]. But to convey the basic problem that
  • 3.
  • 4.
  • 5. mundane activity. The great strength of multi- touch is letting multiple people work together on a complex activity. It is hard to remember how LED liberating the mouse seemed when it freed peo- ple from keyboard arrow keys some 25 years [HOW IT WORKS] ago. Soon the multi-touch interface could help untether us from the ubiquitous mouse. “It’s Tracking Fingers Pressure-sensitive polymer Internal reflections very rare that you come upon a really new user The most advanced multi-touch interface,” Han says. “We’re just at the begin- Light ning of this whole thing.” screens respond to the motion and Reflection scattered pressure of numerous fingers. In the sensor toward reflection [INSIDE LOOK] Perceptive Pixel design ( ), sensor projectors send images through an acrylic screen onto the surface facing the viewer. When fingers or other Touch Table Acrylic waveguide objects (such as a stylus) touch the A projector inside Microsoft’s Projector surface, infrared light shone inside the multi-touch table, called Infrared cameras Image from acrylic sheet by LEDs scatters off the projector Surface, sends imagery up fingers and back to sensors. Software through the acrylic top. An interprets the data as finger move- LED shines near-infrared light LED up as well, which reflects off ments. Tapping the screen brings up To create a signal, LEDs bounce light through the acrylic command menus when desired. objects or fingers back to var- sheet. No light escapes. But if a finger is placed against the ious infrared cameras; a com- Computer face ( ), light will scatter off it toward the sensors. puter monitors the reflections Also, a pressure-sensitive coating flexes when pressed to track finger motions. Computer firmly or lightly, making the scattered fingertip signal appear slightly brighter or dimmer, which the computer Projector interprets as more or less pressure. LED light source
  • 6. Ventromedial prefrontal cortex Nucleus accumbens ex- Subthalamic nucleus Mediodorsal thalamus bbs Motor thalamus ba- Globus pallidus um- internal segment tine ver, Ani- the Anterior rive cingulate cortex mak- ckly mar- iven Amygdala Anterior limb es— of the internal ion, Ventral tegmental area capsule gic. BRAIN AREAS that become gni- n be activated in response to Subgenual n of reward or risk include those cingulate shown above, among others. nan- Nucleus accumbens Orbitofrontal HOW cortex Ventral Lateral pallidum hypothalamus Brain stem Thalamus WHERE Sensory thalamus WHAT Pedunculopontine nucleus Periventricular gray/periaqueductal gray
  • 7.
  • 8.
  • 9. [AFFECTED NATIONS] WORLDWIDE RESISTANCE Tuberculosis occurs in virtually every country in the world, although it is most wide- spread in developing nations. The incidence of TB caused by strains of resistant to two or more of the first-line drugs for the disease — so-called multidrug-resistant TB (MDR-TB) — has been rising as a result of improper use of antibiotics. Worse still is exten- sively drug-resistant TB (XDR-TB) — a largely untreatable form identified in 2006; as of June 2008, 49 countries had confirmed cases. Sadly, that figure most likely underesti- [INFECTION BASICS] mates XDR-TB’s prevalence. AN ILL WIND TB Brain Tuberculosis, caused by the bacterium , occurs in both latent and active forms. People can become infected by breathing in even just a few bacteria released into the air when those with active TB cough, spit or talk. causes coughing, the most familiar symptom, because it accumulates abundantly in the lungs, but it can harm other organs as well ( ). Reported cases of Lung tends to concentrate in the air sacs, or alveoli, of the tuberculosis per lungs because it prefers environments rich in oxygen. In 100,000 citizens it it Macrophage most people, the immune system is able to keep bacterial No estimate replication in check, dispatching defensive cells known as macrophages to the site of infection, where they 0–24 form a shell around the bacteria. But in 10 percent of 2 25–49 Alveolus infected individuals, breaks down the shell, after which it can begin to multiply. 50–99 100–299 300 or more Mtb Kidney Multidrug-resistant TB Scan highlights infection in lung. Bone Unfettered by the immune system, the bacteria destroy the tissue of the lungs; some may also make their way into the bloodstream and infect Percent of MDR-TB f other parts of the body, including the brain, kidneys and bone. Eventually among new TB cases affected organs may sustain so much damage they cease to function, and 1994-2007 the host dies. More than 6% 3 3%–6% Less than 3% the problem is that bacteria are autonomous some of those proteins might be worth consid- No data life-forms, selected throughout evolution for ering as drug targets. Analysis of the TB genome their ability to adapt and respond to external also hinted that, contrary to conventional wis- threats. Like modern aircraft, they have all dom, the bacterium is perfectly capable of living Extensively drug-resistant TB manner of redundancies, bypasses, fail-safes in the absence of air— a suggestion now verified. and emergency backup systems. As Jeff Gold- Under such anaerobic conditions, Mtb’s metab- blum’s character in Jurassic Park puts it, life olism slows down, making it intrinsically less finds a way. Until we truly appreciate the com- sensitive to existing antibiotics. Targeting the plexities of how TB interacts with humans, new metabolic elements that remain active under drugs against it will remain elusive. The good these circumstances is one of the most promis- i h ki h i i f h i i
  • 10.
  • 11. [STAGES TO WATCH] From Animal Microbe to Human Pathogen The process by which a pathogen of animals evolves into one exclusive to humans occurs in five stages. Agents can become stuck in any of these stages. Those in early stages may be very deadly (Ebola, for example), but they claim few lives overall because they cannot spread freely among humans. The better able a virus is to propagate in humans, the more likely it is to become a pandemic. [PREVENTION PROPOSAL] DISEASE EXAMPLES: Reichenowi malaria Rabies Ebola Dengue HIV Building a Surveillance Network By monitoring microorganisms in wild animals and the people who are frequently exposed to them, scientists may be able spot an emerging infectious disease before it becomes widespread. To that end, the author recently organized the Global Viral Forecasting Initia- tive (GVFI), a network of 100 scientists and public health officials in six countries ( and ) who are working to track potentially dangerous agents as they move from Stage 1: Pathogen is present in animals into human populations. The GVFI focuses on tropical regions ( ) in particu- animals but has not been detected lar, because they are home to a wide variety of animal species and because humans there in humans under natural conditions. commonly come into contact with them through hunting and other activities. Eventually the GVFI hopes to expand the network to include more countries with high levels of biodi- Stage 2: Animal pathogen has been trans- COUNTRY: Cameroon versity, some of which are shown here ( ). VIRUSES PREVIOUSLY SPAWNED: HIV COUNTRY: China mitted to humans but not between humans. SENTINEL POPULATION UNDER STUDY FOR NEW PATHOGENS: VIRUSES PREVIOUSLY SPAWNED: SARS, H5N1 People who hunt and butcher wild animals SENTINEL POPULATION : “Wet market” workers Stage 3: Animal pathogen that can be trans- mitted between humans causes an outbreak of disease but only for a short period before dying out. Stage 4: Pathogen exists in animals and undergoes a regular cycle of animal-to-human transmission but also sustains long outbreaks arising from human-to-human transmission. SOURCE: Stage 5: Pathogen has become exclusive to humans. COUNTRY: Democratic Republic of the Congo Nature, VIRUSES PREVIOUSLY SPAWNED: Primary study site (human and animal testing) Tentative site for future study Marburg, monkeypox, Ebola Secondary study site (animal testing only) Tropical region COUNTRY: Malaysia SENTINEL POPULATION : VIRUSES PREVIOUSLY SPAWNED: Nipah People who hunt and butcher wild animals SENTINEL POPULATION : Wildlife hunters
  • 12.
  • 13. [WHAT ASTRONOMERS LOOK FOR] Glowing in the Dark Infrared Light Reveals Disks and Thus Planets or Their Building Blocks A stronomers generally detect planets indirectly, by virtue of their effects on the velocity, position or brightness of their host stars. For most of the cases discussed in the A circumstellar disk of dust and gas, like the one that gave rise to the planets of our solar system, absorbs starlight and emits infrared radiation. We observe a composite of direct starlight and disk emission. article, astronomers focus on one type of indirect sign: the presence of a disk of dust orbiting the star. A so-called protoplanetary disk occurs around newly born stars and is thought to be the site of planet formation. A so-called debris Starlight disk occurs around mature stars and is thought to arise from collisions or evaporation of comets and asteroids, thus Circumstellar disk signaling the likely presence of planets now or in the past. Observers identify both types of disk from how they absorb starlight and reradiate the absorbed energy at infra- Light from disk Star red wavelengths ( ). NASA’s Spitzer Space Telescope, launched in 2003, has proved to be a veritable disk discovery machine. Its large field-of-view infrared cameras can cap- ture hundreds of stars in a single image and pinpoint those with evidence of disks for further study. Spitzer builds on the successes of past infrared telescopes, such as the Infrared Astronomical Satellite (IRAS) mission in the 1980s and the European Space Agency’s Infrared Space Brown dwarf plus disk Brown dwarf Observatory (ISO) in the mid-1990s. Unlike IRAS, which was Disk an all-sky survey, Spitzer points at specific celestial bodies for intensive study, and the five-year-plus lifetime of its liquid- An example is the brown dwarf OTS 44, Brightness (arbitrary units) helium coolant far exceeds that of any previous mission. The whose spectrum ( ) initially telescope has studied everything from extrasolar planets to falls off at infrared wavelengths but then flattens — indicating that the dwarf, galaxies in the early universe. whose spectrum would be expected to peak at The coolant is now running out, and the telescope will short wavelengths ( ), is surrounded by soon start to warm from nearly absolute zero to 30 kelvins. cooler material whose spectrum peaks Even so, it will be able to operate at the short-wavelength at longer wavelengths ( ). end of the infrared band through at least the middle of 2011. Even when the system is Taking up the slack will be the newly launched Herschel too far away for telescopes Space Observatory and the James Webb Space Telescope to resolve spatially, the spectrum 1 3 10 30 (JWST), planned for launch in 2013. — reveals the blending of light. Wavelength (microns)
  • 14. [BASICS] Vaccines Mimic Infection to Avert It IMMUNE MEMORY Some of the B and T cells become long-lived memory Vaccines deliver a killed or weakened pathogen, or pieces of it, to trigger an immune response that generates “memory” cells primed to cells, standing guard against a future infection. recognize the same microorganism quickly in the future. These cells can later block true infections or at least minimize illness. Killer T cells Cytokines innat Attempted infection Memory T cells and B cells COMMON ling f Virus fragments V VACCINE TYPES ropha Dendritic cell ■ ATTENUATED: Live des Injection but weakened whole c site virus or bacterium. T cell precursors Infected cell Minimal reproduc- Virus in Helper T cells tion extends vaccine immune cells’ exposure to antigen t Maturation without causing disease. can and migration Infected cells to lymph nodes pe ■ INACTIVATED: Cytokines Whole but “killed” Antibodies and unable to B cell remain in the body as “memory” cells — some- reproduce or to Lymph node times for decades — ready to squelch any at- cause disease. Macrophage Antigen tempted reinfection by the same organism. Vac- ad cines replicate this process by introducing a ■ SUBUNIT: Fragments the whole pathogen or fragments of it that will be of the pathogen, such k VACCINE ADMINISTRATION DENDRITIC CELL MIGRATION AND INTERACTIONS as genetic material A small dose of live but weakened virus is one common form of Loaded with foreign material (antigen), dendritic cells mature and migrate recognized as a foreign invader. Not all vaccines or external pro- vaccine. Injected into the skin, the virus will infect some cells to lymph nodes to interact with T cells and B cells, components of the succeed in generating a full immune response, and reproduce slowly. “Innate” immune system cells, such as “adaptive” immune system. Displaying antigen and emitting cytokines, teins, provide macrophages and dendritic cells, engulf and digest foreign the dendritic cells induce T cells to mature into helper and killer types; the but some pathogens can be stopped by antibod- antigen for immune material and infected body cells. Dendritic cells also emit helper T cells also signal to incite the killer T cells to attack infected cells ies alone, so killer T cells are not needed for cells to recognize. l signaling chemicals called cytokines to sound an alarm. and induce B cells to produce antibodies tailored to the pathogen. protection. The nature of the pathogen and how it causes ill i d i ’ id [VACCINE BOOSTERS] Adjuvants PATHOGEN RECOGNITION TLR NATURAL TRIGGER Add Emphasis Dendritic cells contain Toll-like receptors (TLR) that each recognize ●● ● 1 2 6 Bacterial lipoproteins molecules typical of many pathogens, such as bacterial proteins or ● 3 Double-stranded RNA distinctive viral gene motifs ( ). Adjuvants that trigger Lipopolysaccharide (LPS), one or a combination of TLRs can simulate different natural threats. ● 4 Adjuvants enhance immune responses to vaccine heat-shock proteins, antigens by several mechanisms, but their most Killer T cells respiratory syncytial virus ●5 Bacterial flagellin protein potent effects are likely to be through activation IL-12 ●● 7 8 Single-stranded RNA of microbe-recognition receptors on dendritic Bacterial CpG DNA Cytokines ●9 cells. Depending on the type of threat they sense, ● 10 Unknown dendritic cells will direct other immune cells to ● 11 Bacterial profilin protein respond in different ways. Vaccine designers Helper T cells Toll-like receptor can use this knowledge to choose adjuvants that will not only boost immune response but also IL-12 DENDRITIC CELL DIRECTIONS Dendritic cells’ signaling determines emphasize the desired responses. how T and B cells will mature and proliferate. For example, the cytokine Antibody-inducing helper T cells interleukin-12 favors development of killer T cells and a helper T subtype lar keys, a group known as the Toll-like recep- needed to defend against intracellular IL-6 tors (TLRs) seemed most important for driving pathogens, whereas IL-6 favors a the dendritic cells’ behavior [see “Immunity’s helper T type that induces B cells to produce antibodies. IL-6, together Early-Warning System,” by Luke A. J. O’Neill; Inflammation-inducing helper T cells with IL-23, induces still another helper S��������� A�������, January 2005]. T subtype that promotes inflamma- IL-6 tion. Interleukins themselves are also To date, 10 functional Toll-like receptors under study as adjuvants. have been identified, and each recognizes a dif- IL-23 ferent basic motif of viruses or bacteria. TLR-4