chapter 1

Antl,ct·ni,

Overvie,v of the •

~,-,...... ,
pr ptid<'

Imn1une Syste111 l.,;,-J MIIL

\I T-n ·II
H r('n ."ptor

/T HE
) C DH

IMMl~E SYSTE."1 EVOLVED ro PROTECT M ULTICELLULAR ) CD4 Vlru~lnkct" d un

organisms from pathogensl Highly adaptable, it de-
fends the body against invaders as diverse as the
virus that causes polio and the flatworm that causes schisto- T-ccll rcw~11it11111 11( 1111t1~c11 -,\ III <
somiasis_1The immune system generates an enormous vari-
ety of cells and molecules capable of specifically recognizing
■ Historical Perspective
and eliminating foreign invaders, all of which act together in
a dynamic network. I ■ Early Studies of Humoral and Cellular
' Protection by the immune system can be divided into two Immunity
related activities--recognition and response. Immune recog-
nition is remarkable for its capacity to distinguish foreign in- ■ Theoretical Challenges
vaders from self components.' The immune system is able to
■ Infection and Immunity
recognize molecular patterns ·that characterize groups of com-
mon path~gens and deal with these in a rapid and decisive ■ Innate and Adaptive Immunity
manner. It can even detect subtle chemical differences that
distinguish one foreign pathogen from another. Above all, the ■ Immune Dysfunction and Its Consequences
system j5 able to discriminate between foreign molecules and
the body's own cells and molecul;s (self-nonself discrimi~a-
tion ). In addition, the system is able to recognize host cells that
are altered and that may lead to cancer.lTypically, rec~gnit~on
of a pathogen by the immune system triggers an__effectoi: re- The recognition elements of the innate immune system pre-
sponse that eliminates or neutralizes the invader. Tl_!e multi- cisely distinguish between self and pathogens, but they are not
ple components of the immune system are able to convert the speGialized to distinguish small differences in foreign
initial recognition event into a variety of_effector responses, molec·ules. A second form of immunity, known as adaptive
each uniquely suited for eliminating a particular type. of immunity, develops in response to infection and adapts to
pathogen." Certain exposures induce a memory response, recognize, eliminate, and then remember the invading
characterized by a more rapid and heightened immune reac- pathogen. Adaptive immunity is contingent upon innate im-
tion upon later attack. It is the remarkable property of mem- munity and begins a fow days after the initial inf~tion. It pro.-
ory that prevents us from catching some diseases a second vides a second, comprehensive line of defense that eliminates
time, and immunological memory is the foundation for vac- pathogens that evade the innate responses or persist in spite of
cination, which is a means of "educating" the immune system them;\ An important consequence of ad,lptive immune re--
to prepare it for later attacks. sponse is memory.\ If the same, or a closely rdated, pathogen
rAlthough reference is made to the immune system, it must infects the body, memory cells provide the means for the
be pointed out that there are two systems of immunity, innate adaptive immune.system to m.lke a rapid and often highly ef-
immunity and adaptive immunity, which collaborate to pro- fective attal"k on the invading pathogen. I
tect the body. Innate immunity includes molecular and cellu- This chapter introduces the study of immunology from a

A
V
lar mechanisms predeployed before an infection and poised to historical perspective. The highly practical or applied aspects
prevent or eliminate it. This highly effective first line of de- of immunology are outlined, emphasizing the role of vaccina-
fense prevents most infections at the outset or eliminates them tion in the development of immunology as a scientific fidd
within hours of encounter with the innate immune system. and as an important aspect of public health. A bird's-eye
1
 2 P A ~ T I INTRODUCTION
l
of the common pathogen s to whkh
wr arc l'Xposl'd is ~ivrn,
with a broad overvil'w of thL· pr01:rssc
s, cells, ,md n10lcn iks
thJl m.ike up the innJIL' anJ .-1d,1ptivc
we dcsffihe circumst,11Krs in whkh
imnHllll' systems. 1~1, L:
thl' immunr systl'lll tails
to act or whrn it lx'\:'Omes an a~rl'sso
r, turnin g its ,1wrso me
J'l.'WL'rs a~a inst its host .

Historical Perspective
The di~ipline of immunology grew
out of the _o~serv_a~ion
t hat m. d.1n'J 1 ·ho had recovered from
ua s " certam 1nfeL11ou s
disea..--es were thereafter protected from .
the diseas~. The La~111
term imnrunis, meaning "exempt," is the
source ot the Ei~ghsh
word immunity. meaning the state of
protection from mfec-
tious disease.
Perhaps the earliest written reference
to_ the phenomen~n
of immunitY can be traced back to
Thucydides, the great h1~-
torian of the Peloponnesian War. In
describing a plague m
Athens, he "'Tote in 430 BC that only thos
e who had recovered
from the plague ami d nurse the sick
because they woul~ ~ot
contract the disease a second time .
Although early soCietles
recognized the phenomenon of imm
passed before the ooncept was succ
unity, almost 2000 y~ars
essfully converted mto
\
medically effective practice.

Early vaccination studies led the way

to immunology
The first recorded attempts to induce FIGURE 1- 1 African child with rash
immunity deliberately typi cal of sma llpo x on face.
were performed by the Chinese and Turk chest, and arms. Smallpox, caused
s in the fift~enth cen- by the virus Vario/a major, has a
tury. They were attempting to prev 30% mortality rate. Survivors are ofte
ent smallpox, a ~1sease_ that n left with disfiguring scars.
is fatal in about 30% of cases and [Centers for Disease Control.]
that leaves survivors disfig-
ured for life (Figure l-1) . Reports sugg
est that the dried crusts
derived from smallpox pustules were
either inhaled into the
nostrili or inserted into small cuts in
the skin (a technique next major advance in immunology
called variolation) in order to prevent , the indu ctio n of irnm u-
this dreaded disease. In Qi_ty t~ chi>lera~Louis Pasteur had succeed
1718, Lady Mary Wortley Montagu, the ed in growing the
wife of the British am- bacterium thought to cause fowl cho
bassador in Constantinople, observed lera in culture, con firm -
the positive effects of ing its role when cn1cken_s injected
variolation on the native Turkish pop with the cult ured bac-
ulation and had the terium developed fatal choler:,.
technique performed on her own child \After retu rnin g from a
ren. The English physi- summer vacation, he injected som e
cian Edward Jenner, in 1798, made a gian chickens with an old bac-
t advance in the de- terial culture. The chickens became
liberate development of immunity. Intri ill, but to Pasteur's sur-
gued by the fact that
milkmaids who had contracted the mild prise, they recovered. 'P.isteur then
disease cowpox were grew a fresh cult ure of the
subsequently immune to the much mor bacterium with the intention of inje
e severe smallpox, Jen- cting it into som e fresh
ner reasoned that introducing fluid chickens~ But as the story is told, his
from a cowpox pustule supply of chickens was
into people (i.e., inoculating them) mig limited, and thert•fore he used the
ht pro kct them from previously injected chick-
smallpox. To test this idea, he inoculate ens. Unexpectedly, the chickens wer
d an eight-year-old boy e completely pro tect ed
with fluid from a cowpox pustule and from the disease. Pasteur hypothesize
later intentionally in- d and pro ved that aging
fected the child with smallpox. As pred had weakened the virulence of the
icted, the child did not path oge n and that such an
develop smallpox. a~tenuated strain might be adm inis
tere d to pro tect against the
Jenner's technique of inoculating with d1s~ase. He called this atte nua ted stra
cowpox to protect in a vaccine (fro m the
agamst smallpox spread quickly thro Latin vacca, meaning "cow"), in hon
~ghou~ Europe. How- or of Jenner's wor k with
ever, it was nearly a hundred years cowpox inoculation.
before this technique was
app ll-..~ d to other diseases. As. so often happens in science, P~ steur ext~nded these findings to
oth er diseases, dem on -
· ,·ry in com bination with astu . stra tmg that it was pos sibl e to
w·rrm jIp te observation led to the atte nua te, or weaken a
pathogen and administer the atte nua
ted strain as a vacdne.' In
 , .. ..,

fromrlu tu,,dh, lfnnnmr h~ 1 ·,,.., ~(tt<'IV•l'lf'™"'""'_.,,t

, . 1
I
k 111111n ,, th,.i 1111,"rr,AI vA,, tn,H111n t,,.( ,,Tll4'.'I 11nr;,•r, ...... ,., ,,.,..
j, 11 trrm,-11 ,11111~ •~n,f,, tl!"1.t11~ ,~ m,.~il~"" n,, ,.,_ ,..-rrorrl
a ,lt~hl (k 1£fM' of m► ,,, rt''"'"' u, • tn.t,,<I -111 w,11 "" 1,, P"'
"""' npovd '" ff'( mt V .t( \ lf1t'('' f h,,,. i-. ' d-1 r~,r •11 I, h, ,w
rvrr, to rr.td1c .itton .tnd th, rn,l nf •HH"trul "~-• in.trtnfl 1 ,.,,.,
111nr, thr n11mht-r of r-'"~•lt w,rh no 1r,,m11n,1v 'n rh# tf,.,,.~
w,11 nt'\f\\.,mly ri~ ,·rt nnt J.,y t~ <t,-.,.t'l4' m.JV h,, ,,.,n,r...
dou·cl h)· unn.tlllr.tl m<.tn\ In fM.I, •m.1ll rn"{ '" ',,n•rn-k,,.J '~
of 1hr mml polrnr hroltrror,~m rhrtd14 In rt,rnn-w n,w ,n,i
'-llt-r ~·au tnt', A>(,1111'1 ,m.ill ~..-" ur ht,°' ,-kv,t, ,r,d
A milntonr m VM.onol,iv ,omr.1r .thk to ffll.tllPo" tr 11h-
ta tion m.iy ht- •roun<t tht ,01f'W'.r fnr p-1r.1tvt1C p,.h,\. • ~rip-
pling di\t:.l'( t.ir~1ed for uMi K.th<,n m rht rw.ar futurt. "
camp,1ign \pe.irhr.idt'd hv tht World Ht.itfh C>runi1.1rt.on h.-
relicd on ma.\ \ivr immuni, .itH,n pr,~ .am• tn ,.rv out th..-i
objective. The project ~ ,lowed t-,y rf\1~.irxt in ctrt,un • ~
based on rumors that immun11~tion u~ lt~nhrv "' mdk
children. The regional rnurgenct m polio C..t\<'1 in ~.un
areas of Asia and Africa resulting from tht1 r~t.~.lnce • • 'W't·
back, but one that can be overcome by tdULM,oft md ,>bwrv.it-
tion of the benefits of vaccination. The fact th.It pouo 111 no< ~
threat worldwide and has been eliminated m l'IIO'lt u,untnn 11
a triumph that should not be ove~ c d ~ dd,m in the
eradication program.
In the United States and other industri..iliud n.itJom.. V.M>
cines have eliminated a host of childhood dis<-.asn th.at wtre
FIGURE 1-2 Wood engraving oflouis Pasteur watching Joseph considered a part of growing up just 50 ~~.ars Agt>. '.\. k-.&:Jo.
Meister receive the rabies vaccine. {From Harper's Weekly 29:836; mumps, whooping cough (pertussis ), teunus. d.iphth<n.i. mJ
courtesy of the National Ubrary of fv1edicine.] polio are extremely rare or nonexistent °b(cause ot currmt
vaccination practices (Table 1-1 ). One cm b.irelv otim,uc uw
savings to society resulting from the prevention \M. ~ ~
a now classic experiment performed in the small village of eases. Aside from suffering and mortality, ~ roc;t to ttt-.at
Pouilly-le-Fort in 1881, Pasteur first vaccinated one group of these illnesses and their aftereffe(ts or Sc.'(\Ud,ie \~ch ~ p.u.al-
sheep with heat-attenuated anthrax bacteria (Bacillus an- ysis, deafness, blindness, and mental retan.l.ltion) t> lfiU!k."nS(
thracis); he then challenged the vaccinated sheep and some and dwarfs the costs of immunization.
unvaccinated sheep with a virulent culture of the anthr~ For some diseases, immunization is the- bc!-st, if lK.' l the- onlv.
bacillus. A1J the vaccinated sheep lived, and all the unvacci- effective defense. Because few anfr,iral drugs are now .i,atl-
nated animals died. 'Ibese experiments marked the begin- able, the major defonse against intlue1u.1 mlb't b< .rn effn fru:
nings of the discipline of immunology. In 1885, Pasteur vaccine. If an int1uenza p.indemic rn:ur$. as pn.'\.lh:tt:J b~
administered his first vaccine to a human, a young boy who many experts, there will be a race between its spre.iJ .i.nJ the
hacf been bitten repeatedly by a rabid dog (Figure l -2). The manufacture and administration of an effectiw ,-.Kcine ..\t the
boy, Joseph Mei~ter, was inoculated with a series of attenuated time of this writing, much attention is hein~ p..uJ to ,m emerg-
rabies virus preparations. He lived and later became a custo- ing strain of avian intluema. About 200 c.is~ of inhti1.ln in
dian at the eponymous Pasteur Institute. humans have been donunentc:d, of which abo\lt h.uf were
fatal. If this virus adapts to spread efficiently in hum.ms., a
Vaccination is an ongoing, worldwide major pandemic will mult. Without a preventative v.iccine,
enterprise the devastation caused by the intlut'nza p.mdemic of 1918,
which lctt as many as SO million dead, may be equah.·d or
The emergence of the study of immunology and the discovery surpassed.
of vaccines are tightly linked. The discovery, development, and Despite the record of success for vaccines and our re-
appropriate use of vaccines remains a challenge to immunol- liance on them, opponents to vaccination programs have
ogists today. made claims that vaccines do more harm than good and
In 1977, the last known case of naturally acquired smallpox that childhood vaccination should be curtailed or even
was seen in Somalia. This dreaded disease was eradicated by eliminated. There is no dispute that vaccines represent
univmal application of a vaccine that did not differ greatly unique safety issues, since vaccines are given to people who ,

/4
 IN l R<'Olll 1 ll'N

l ~ Ol E 1 - 1

ANNllAl CA'il'i/YR
Oi,.._ Pr•v auin e Postvacclne lwduction (%}
~~
'48,lb 4 0 100
Dlf' t\t~ a
175,885 0 100
"4ea~
503,282 37 99.99
Mumps
152,209 236 99.85
~ USM!, (whoor•"I cough) 147,271 18,957 87.13
Parlt lytK polio
16,316 0 100
~ub@ty (~ mNs&.s) 47,745 12 99.97
T~ r\odja-.,r,,")
1,314 (deaths) 26 (cases) 98.02
~ hemophilus inft ~z• 20,000 172 99.14
SOU la ~ from W. A.. ~
"' et ll., 2005. HNlth Affairs Z-4:599.

are heal thy. Furt herm ore, there is gene

ral agreement that
vau. ines mus t be regulated and the publ
to d ear and com plete info rmat ion abou
ic mus t have access '1a rly Studies of Humeral and
t them. Although
the claim s of critics mus t be evaluated, man
y can be an-
Cellular Immunity
~cr ed by careful and objective exam
ination of records. A Pasteur proved that vaccination worked,
rece nt exam ple is the claim that the but he did not un-
merc ury- cont ainin g derstand how. The experimental wor k
pres erva tive thim eros ol, previously of Emil von Behring
used in some vaccine and Shibasaburo Kitasato in 1890 gave
prep arat ions , causes autis m and was
responsible for recent the first insights into
incre ases in the incidence of the disorder, the mechanism of immunity, earn ing von
which is mark ed Behring the Nobel
by inte nse self-absorption and inability prize in med icine in 1901 (Table 1-2)
to relate to others. . Von Beh ring and
Auti sm generally manifests itself betw Kitasato dem onst rated that seru m (the
een 1 and 2 years of liquid, noncellular
age, the time wind ow in which many vacc com pone nt recovered from coagulated
ines are given (see bloo d) from animals
Cha pter 19 ). The Danish government previously imm uniz ed to diph theri a coul
maintains meticulous d transfer the im-
heal th records on its citizens, a source mun e state to unim mun ized animals. In
of data that throws search of the protec-
revealing light on the putative causal tive agent, vari ous researchers duri
conn ectio n between ng the next decade
thim eros ol and autism. The records demonstrated that an active com pone nt
indi cate d that the from imm une seru m
incid ence of autis m increased significa could neutralize toxins, precipitate toxin
ntly since 1992 in s, and agglutinate
Denmark. However, the records also show (clump) bacteria. In each case, the activ
ed that the use of e agent was named for
thim eros ol as a vaccine preservative the activity it exhibited: antitoxin, prec
had already been ipitin, ~d agglutinin,
nop ped completely in that coun try respectively. Initially, different seru m
several years earlier. com pone nts were
Data such li these make it difficult to link thou ght to be responsible for each activ
autismJ;e-the-use- ity, but duri ng the
of thimerosol and suggest the need for 1930s, mainly thro ugh the efforts of Elvin
furth er research into Kabat, a fraction of
the cau!>es for the increase in autism. serum first called gamma globulin (now
imm unog lobu lin)
Perhaps the greatest current challenge in was shown to be responsible for all these
vaccine develop- activities. The active
ment is the lack of effective vaccines for molecules in the immunoglobulin fract
major killers such as ion are called anti-
malaria and AIDS. It is hoped that the bodi es. (The terms antibody and imm
immunologists of unoglobulin may be
today, U!>ing the tools of molecular and used interchangeably, but usually the term
cellular biology, ge- antibody is reserved
nomics, and proteomics, will make inroa for immunoglobulins with known specificit
ds into preventing y for an antigen.)
these diseases. A further issue in vaccines Because immunity was mediated by antib
is the fact that mil- odies contained in
lions of children in developing countries body fluids (known at the time as humors),
die from diseases it was called hu-
that are fully preventable by available, moral immunity.
safe vaccines. High The observation of von Behring and Kitas
manufacturing costs, instability of the prod ato was applied to
ucts, and delivery clinical practice. Prior to the advent of antib
problems keep these vaccines from thos iotic therapy for in-
e they could greatly fectious diseases, antisera, often prepared
benefit. This problem could be alleviated in horses, were given
in many cases by de- to patients with a variety of illnesses. Toda
velopment of future-generation vaccines y there are therapies
that are inexpensive, that rely on transfer of immunoglobulins,
· heat stable, and administered without and with the devel-
a needle. opment of monoclonal antibody technology
, antibody therapy
 nv,•vuw ()f THf IMMtJNf \1\flM
rNA,fft I 5

TABLE 1-2 Nobrl pri1~s for immunologic re\earrh

Ytar Rtc ipl.nt Country ~we,ch

1901 lmil von 8,hnna C,.rmany S.rum ,nti,l'JJint

1905 Robert Koch Gt'rmany (,111,fa,> lfflffVl"- f to tub-fr ,~
1908 [lie M,tchnikoff Ruula _,. of pt'l• ff-,.,,,,.. (~r~rl'j ,vi
Paul Ehrlith Gtrmany ,nt,t(Jlr,nt ((twldlj.,, ~ ,
1913 Charles R1chet FranCf An.,phyi a1t1
1919 Jules Bordtt Belgium ~ -m-.dt-td b,r:~,t)f,,,.
1930 Kart Landsteiner United States Otscowry r,f ~ i,4r,rJll'.I IV?JO'S
195 1 Ma1< Theiler South Africa 0t-.t'°9mfnt r,f.,..,,,,
~ «ClfW

1957 Daniel Bovet Switzerland Ant1h11t~

1960 F. Macfarlane Burnet Australia 01scovtry of KqUWtd ~. . .
Peter Medawar Great Britain to&.rlfU
1972 Rodney R. Porter Great Britain Chemiu& structure ol M l t ~
Gerald M. Edelman United States
1977 Rosalyn R. Yalow United States Development ° ' ~
1980 George Snell United States Major histoc:ompat,t,,uty a,mp(o
Jean Dausset France
Baru j Benacerraf United States
1984 Cesar Milstein Great Britain Monoclonal antilodits
Georges E. Kohler Germany
Niels K. Jern~ Denmark Immune r ~ theanes
1987 Susumu Tonegawa Japan Gene rearrangement in antibody
production
1991 E. Donnall Thomas United States Transplantation imnuloqy
Joseph Murray United States
1996 Peter C. Doherty Australia Role of major histocompatibii
Rolf M. Zinkernagel Switzerland complex in antigen recognition by T cel'5
2002 Sydney Brenner S.Africa Genetic regulation of orpn
H. Robert Horvitz United States development and eel deattl (apopcosis)
J. E. Sulston Great Britain

is now a well-established commercial enterprise (see Clinical In 1883, even before the discovery that a serum u>mpon<nt
Focus in Chapter 4). Emergency use of sera containing anti- could transfer immunity, Elie Metchnikoff dt-monstrateJ th.it
bodies against snake or scorpion venoms for bite victims is a cells also contribute to the immune st.ite of an animJl Ht ob-
common practice. Whereas a vaccine is said to engender active served that certain white blood cdls, whkh he tem'k!'\l phago-
immunity in the host, transfer of antibody with a given speci- cytes, ingested (phagocytosed) microorganisms and othtr
ficity confers passive immunity. Newborn infants benefit from foreign material (Figure 1-3). Noting that th~ phJ~°'-~
passive immunization conferred by the presence of maternal cells were more active in animals thJt h.id been immWlizoo,
antibodies in their circulation. Passive immunity may be given Metchnikoff hypothesized that cdls, r-.ither thJn serum com-
as a preventative (prophylaxis) to those who anticipate expo- ponents, were the major effector of immunity. The active
sure to a given disease or to those with compromised immunity. phagocytic cells identified by ~ktchnikoff were likely blood
Antisera to certain bacterial toxins such as diphtheria or monocytes and neutrophils (see Chapkr 2).
tetanus can be administered to infected individuals to stop the
disease caused by the toxin. A dramatic vignette of this appli-
cation was the relay of dogsleds racing over 674 miles of
frozen Alaskan landscape to bring diphtheria antitoxin from
Theoretical Challenges
Fairbanks to the affected children in the icebound city of Whereas development of safe and effective vaccines and the
Nome during a diphtheria outbreak in 1925. The successful use of passive immune therapy remain challenging problems
outcome is commemorated annually in the Iditarod dogsled in clinical (also called translationaO research, the study of im-
race, and there is a statue of Saito, one of the lead dogs used munology also raised puzzling theoretical questions that oc-
for the final leg of the delivery, in New York's Central Park. cupied the scientific community.
 tin
co f n g ea rly im m un o\ 0 _
l ln r
. .iu
ol IIit r •,it c11 1g1 r1JS n. ro dy mo lec c c .
f I a nti 1JO ule 1or 1o re1gn
t, v. 1, t Iw 'I'',.~ ·,tt~ it Yo t ,e rn for a su bstan ce
·
11,1, •I
m,,l l'" •' . or a nt joc n ( t hr ~c ncr aI tc rnd that
" ·1 ly) Arou 19 00 , Iulcs Bo rd et
b1111I, wi1h a ~pni hl at
"11111m 11.:: d th e f . .
th e \',1,lcllT 111 ~1,tutc e'l( n,J Ol
- co nc ep t o ,hmmun1
. - r C'I hy dc rn o n,; t"ng t at no nty
I,l· vn nlI ·
, ,,t cctio u~ J" cJ "' tr a ' -
' ,1h111.1c11i( 11\l b .. tan ll'S h as re d h\o od cel ls fro m other
\' r-
, su e Cn ru rn from an an im . ·
' \'t' l ic, l 1111 \d
!1-crve as c1 nt wc n'I . ."l' al lnO c-
h
. 1 would neve rt c·Iess react
" •
ulJt n l with noni nfe cti. ma terta
ous . h k
with the in in tcd mJ ·c11 tn a specific m an ne r. T e wo r of
tcn h fo llo wed hi.m s h d
K,irl Li ml.,tc1ncr an d those w O owe t hat
· or ga nic · I
. .
inil'( tin~ an antm a I ith alm os t any
w
ch em tca co u Id
. . . d .fi
.
ind u(e prod uctio n o f nt1bod1 es t a h t wo uld b in spec 1 ca 11y
a . d
to the ch cmirn l. The~ tud1es emo ns tra ted th at anti.bo d'1es
s .
ftC UR E 1-3 D.- have a ca padt y for an !most un 1im• •te d ran ge of react1.v1. ty,
u - - . _ ..... . . . a d th at ha d only recently
- - · -.. oa in g a fOaw in g by Elie M tch · m du dm g res po nses tO co mp ou n s
f'eign . . d · h laboratory d had no t previo . I
rv. -v-,_.,
,.,.. ......_ ~ .. 0 f ph e nikoff of phagocyti been synthe siz e in t e an us y ex-
ceUs [ ag ~ ,.o si pa .rti de .. He fi rst d c cells
isted in natu re. In a dd ' ·
. h wn th at m olecules .
it1on ~ it waId
·1-.- ..1
. -- '~
· By pe rm ;s.s io n o f Of ing es tio n of f · es cn v= i an d named the
s. ss o d1f-
TL - .. . fering in the sm~lle 5t be di sti ng ui sh ed by the
sh Ubra ore ,gn ma tte r by white ir
·-
Co m pa rat ive Pa tho4ocn," ,ef 8 rrt1 .761 blood detail_ c; ;. Two ma
.
stitu te fl . 'Y- 6 reactivity with differ jo r th eo rie s were
proposed to accountent antib ie~.fi ·ty· th e selective th eo ry
in 18 9 1 tra -<:: ,J o In am ma t,o n .h. 19, Lectures on the
• ns Iat ed by F A d t·
by ll 'ya l/'k:t, Mec r e ivered at the Paste for this speci ca ·
hn it · · 5tar mg and E. H. ur In-
°"'· 18 9 3
• p . 64, fig. 32.}
Sta rling, wit h plates
and the instructional
Th e earliest concep theory.
tion of th e se 1ectiv · theory da tes to
O ne Paul Ehrlich in 1900 e . h . . f
of ce llu lqu es tio
d h
n th at su rfa d
· se ru m antibody, Ehrli
. In an att em pt to ex
pla_m t e on gm 0
ar an . ce ea rly inv ch pr op os ed th at cells 10 th
~ ·ee n th um or al un m . A olved th e relative roles pressed a va ne . ; ?l oo d e~-
os e " 110 he um ty . co nt ro ve rsy ty of receptors, w h'lC h he ca lle d s1
developed de-cham
an d th os e w ho ag ld to th e co nc ep t of hu m or al im mu ni ty receptors," th at could .
react wi th in fe cti ou .
m ed ia te d. re
. ed w ith Metchnik.off's co nc ep t of cell- tivate th em . Borrowi s agen_ts a_nd ma~-
IID ID Ui llt y. It . 1894 to explain the
ng a co nc ep t us ed by
Em il Fi sc he r ~n
IS no w ob vi ou
th e full im m un e s th at bo th are co rr int era cti on be tw ee n
re sp on se re qu ire s ec t- substrate, Ehrlich pr an en zy me an d its
responses.. Ea rly stu bo th cellular an d hu op os ed th at bi nd in g
di es of im m un e ce mo ra l an infectious agent of th e re ce pt or to
la ck of ge ne tic al ly lls we re hi nd er ed by was like th e fit be tw
de fin ed an im al m od els the Ehrlich suggested th ee n a lo ck an d key.
cu ltu re te ch ni qu es an d m od er n tissue at in ter ac tio n be tw
, wh er ea s stu di es agent an d a cell-bo ee n an in fe cti ou s
ta ge of th e re ad y wi th se ru m to ok ad und receptor wo ul d
av ail ab ili ty of bl oo van- produce an d release in du ce th e cell to
ch em ic al te ch ni qu d an d established bi more receptors wi th
es to pu rif y pr ot ei o- (Figure 1-4). Accord th e sa me specificity
im m un ity . In fo rm n me di ato rs of hu mo ing to Ehrlich's th eo
at io n ab ou t ce llu ra l th e receptor was de ter ry , th e specificity of
lagged be hi nd th e lar im m un ity theref mi ne d in th e ho st be
un ra ve lin g of hu m ore to antigen, an d the fo re its ex po su re
In a key ex pe rim en or al im mu ni ty . antigen selected th e
t in th e 1940s, M er tor. Ultimately, all ap pr op ria te re ce p-
Th e Ro ck ef el le r In r~ Chase, wo rk in g at aspects of Ehrlich's
sti tu te , su cc ee de d pr ov en correct wi th th eo ry wo ul d be
against th e tu be rc ul in tra ns fe rri ng im mu ni ty the mi no r ex ce pti on
os is or ga ni s~ by tra exists as bo th a solub th at th e "re ce pt or "
ce lls be tw ee n gu n~ fe rri ng wh ite bl oo le an tib od y molecule
in ea pi gs . Un til th d receptor; th e soluble an d a ce ll- bo un d
ve lo p an ef fe cti ve at po m t, attem_pts fo rm is secreted ra th
va cc in e or an tib od to de- fo rm released. er th an th e bo un d
cu lo sis ha d m et y th er ap y ag ain st tub
w ith fa ilu re . Th us _er- In the 1930s an d 1940
h lp ed to re ki nd le , Ch as es d~mons~ran s, the selective th eo ry
<:m by various instruction was challenged
in ter es t in ce llu lar al theories, in which
e im mu ni ty . W ith th central role in deter an tig en played a
em er ge nc e o f im . e
pr ov e d cell cu ltu re tec hn iq ue s in th e 1950 molecule. According
mining the specificit
y of th e an tib od y
h I ph oc yt e wa s .d t "fi d as th e ce . I s, to the instructional
t e ym 1 en I e ll respons1b e 1or bot h
c
lar antigen would ser theories, a pa rti cu -
l.
ce ll u lar .an d hu m or a 1m m um·ty• So on th er ea fte r, ex pe rim en ts ve as a template ar ou
•.
. would fold. The antib nd which an tib od y
w ith ch ~c k~ ns _p1 d b Br uc e Gl ick at Miss . . ody molecule would
on ee re t tte re ar e iss1pp1 State configuration comp thereby as su me a
U ni ve rs ity in di ca ted tw o ty pe s of lymph lementary to that of
_ th ~ fro m th ym us ocytes: plate. This concept th e an tig en tem -
T ly ~p ho cy te s, de , me di ate d cellular was first postulated
im - an d Felix Haurowitz by Friedrich Breinl
n~ e es, fro m th e bu rsa in ab ou t l 930 an d
m un 1t y, an d B ly of
m p ~ b' ds ) F~ br ici us (ai:i l 940s .in terms o~
protein folding by Li
redefined in th e
ou tg ro w th of th e we re involved m hu structional theories nus Pauling. Th e in
cl oa ca m a~ou; th mo ra l were formally disprov -
im m un ity . Th e co e roles of hu m or al which time informa ed in the l 960s b
nt ro ve rs { ad \'\·h en an d tion was emerging ab
ce llu la r im m un ity
wa s re so ve lea
th e sy ste ms were sh
ow n protein: RNA, an d DN
A th at would offer
out the structur~ :C
. in ed It be ca m e c r th at bo th sy ste ms were nee- the vexmg problem
of
new insights in to
hl be m te rtw .
. bodies against almos how an individual co ul d make anti-
e- .~ ry fo r th e am un e re sp on se . t anything.
m
 OVI RVIIW Of IHI IM~~IINr \ Y\r!M
1

h11 n1.1n pc1rho)("'1~ liln 1w 1trn111 f'<l

1
1111,, m.11or u1t·;c11rie•,

, hown lwlnw jlflll in I IJ(llrt I -;,

Major 1roup1 of
human p1thog,n1 h•m,,(•1 of diw.wt
--
Virus,5 Pol,o. 1'MliptJ•. infbJ11nz.1.
~~~ - AlfJS

Ba(teria Tu~rcukx1j, tft¥!Vi, wh~

ing cough

Fungi ThMh. rin~m

Parasi tes Malaria. ~1shman1~is

Of major interest here are the meam by which rlfectrve im-

munity to the pathogens can be achieved. An dfective defm~
relies heavily on the nature of the individual microorganism.
For example, because viruses require rmmmali~n cellJ for
their replication and multiplicat ion, an effective deferue
strategy may involve recognizing and killing any ~U that ii
virus infected before the life cycle of the virus can be c.om-
pletedtfor organisms that replicate outside host cells, prompt
recogmtion of these invaders by antibodies or 50Jubk
molecules can be used, followed by cellular and mokcular im-
mune mechanisms that eliminate the pathogen.
FIGURE 1-4 Representation of Paul Ehrlich's side chain theory
Some pathogens that pervade our environment ra~ no
to explain antibody fonnation. The cell is pluripotent in that it ex-
problem for healthy individuals because there is adequate pre-
presses a number of different receptors or side chains, all with differ-
existing immunity. However, individuals with deficiencies in
ent specificities; if an antigen encounters this cell and there is a good
immune function may be susceptible to disease caused by
fit with one of its side chains, synthesis of that receptor is triggered
these ubiquitous microbes. For example, the fungus Candi.Ja
and the receptor will be released. {From Ehrlich's Croonian lecture of
albicans, present nearly everywhere, causes no probkms tor
1900 to the Royal Society.}
most individuals. However, in those with lowered immunity,
it can cause an irritating rash and a spreading infection in the
In the 1950s, selective theories resurfaced as a result of new mucosa lining the oral and vaginal cavities. The rash, callai
experimental data and, through the insights of Niels Jeme, thrush, may be a first sign of immune dysfunction. lf kft
David Talmadge, and F. Macfarlane Burnet, were refined into unchecked, C. albicans can spread, causing systemic candidia-
a theory that came to be known as the clonal-selection theory. sis, a life-threatening condition. Another e.'<ample is the 'tirus
Ac.cording to this theory, an individual lymphocyte expresses Herpesvirus simplex, which normally causes small lesions
membrane receptors that are specific for a distinct antigen. around the lips or the genitalia. In those with deficient immu-
This unique receptor specificity is determined before the lym- nity, these lesions may spread to cowr large portions of the
phocyte is exposed to the antigen. Binding of antigen to its body. Such infections by ubiquitous microorganisms. often ob-
specific receptor activates the cell, causing it to proliferate into served in cases of immune deficiency, are termed opportunis-
a done of cells that have the same immunologic specificity as ti~·infections. ~~veral rarely seen opportunistic inhtions
the parent cell. The clonal-selection theory has been further identified in early AIDS patients were the sign.ii thjt the im-
refined and is now accepted as an underlying paradigm of mune systems of these patients were seriously compromised.
modern immunology. For some pathogens known to cause serious diS(.'~. the
means to achieve -immunity are wdl documented and° allow
control of the disease. For example, tetanus lcom~~nly called
lockjaw)~ caused by a.common soil bacterium (Cfostridium
, Infection and Immunity tetani), which acts through a toxin thal att~ks the nervous
Along with the developing field of immunology grew the ~stem (neurotoxin). Untreated, tetanus leads to deaih-within
study of medical microbiology, which covered the identifica- a short tim~. There is an effective vaccine to tetanus, and
tion of infectious agents and their modes of causing disease. should that fail, antibodies to the toxin can be administered to
Organisms causing disease are termed pathogens, and their offset the potentially fatal disease. Prior to the availability of
means of attacking the host is called pathogenesis. The these prevention and treatment measures, anyone suffering a

,J
 INTR.o
Duc 1 10N

( b)
(d)
FIGURE 1- 5 Pathogens rep
resenting the major categor
mic roo rga nis ms causing hum ies of Photo Researchers.] (c) Fungi: Can
an disease . (a) Viruses: Transmis dida albicans , a yeast inhabitin
elec tron micrograph of rota sion human mouth, throat, intestines, g
virus, a major cause of infant and genitourinary tract; C. albi
Rotavirus acc oun ts for approx diarrhea . commonly causes an oral rash (thru can s
imately 1 million infant deaths sh) or vaginitis in immunosuppres
dev elo pin g countries and hos per year in individuals or in those taking sed
pitalization of about fifty thousand antibiotics tha t kill normal bac
per yea r in the United States. infan_ts flora. {Stem )ems/Photo Research terial
{VEfvt!Photo Researc~er~.} (b) Bac ers .] (d) Parasites : The larval form
Pseudomonas, a soil bacterium teria: filaria, a parasi_ti: worm, being of
tha t is an opportunistic pathoge attacked by macrophages. App
n for mately 120 m1ll1on persons wor rox i-
hum ans , be ing ingested by ldwide have some form of filar
human macrophages. {David M. iasi s.
Phillips/ {Oliver Meckes/Nicole Ottawa/Eye
of Science/Photo Researchers .]

pun ctu re wo un d by a d irty obJ' ect suc h as a rusty nail, was at

risk for a fata l td a nus infe '
ctio n . In ma rked contra~t to_
. the sue - Innate and Adaptive Im m
ces s 1n con tro ll1·n g teta nus is the fa ilure to devise imm une un ity
· . HIV infectio n , wh ich ·
str a teg ies to co ntr a 1 lead s to AIDS · t Imm uni ty- the stat e of protect
. t d _1 wit h all typ es of path oge ns . ion from inc t· d.
T h e 1111111une S)'Ste m
.
mu s ea
.
has bot h a Iess specifi
. - c and a mo re specifi iec 1ous 1sea se-
I . for dea lin g with invasio .
a nd hJ s evo , ,e d mu ltip k stra tegies .
n
d
less spec1h c com pon ent , umate
immunityc com.pon ent · The.:
th , d the first bar rier s of skin line of defe nse against infectio
b)' J p..1 th oge n t ha s pas se an • n Most ' pro vid es th e hr\
a
,wc u,,1 . \\'e will see th at sohm
f these stra tegies are po ise. d
to unm urn·ty are pre sent b e1o c
re · co mp o nen t~ of inn 1tet
l' e o bre ach es th e host's bar • the ons t f • c .
- . rier s; stit ute a set o f dise ase- resistan ce me hO m1e ct1on ::i nd '
... .. '.'"'l'""d th< ms ton t a pat oge n
<d to act after inf ect ion ". establ." h d spe cifi c to a particul ar pat hog ec
. cun -
, . en b a111 . ·I
~m ~ that
.i n· n, ''
~ •' ' " "' d,·k nse s a1< crJfi ' ut me ude cd lu l,1 r ,111, I
 OVIAVl(WOf lHI IM~,~~f \~rf"'
,,. ,, r1 1 I 9

Till'IC'I. ul.ir l,,1111,,ncnt, thdt fr\ ,,111111r d.i,~, 111nmh 11k, J>e · fa11l1t,1tin~ th,·ir <10,,rn,, ( .nmrl,nwnt O(( 11 r 1"• ' P"'"' 1'"1
,uli,1r to ffi'\llll'ntl\' l'n,,"111tcn.-J 1,.1thn~l'm. th.,1 trulv ,tr;id,11~ tht inn.11, .and ;Vt,1ri1~ 1mm,m, w--ruM.
Thr first hurdle for a 1,.ith,,iicn 111n1lvl" hrc.tlhmp. thr hJt· tn thJI u•rt.1m u1mr-10fn" m.1v d1rr, 1ly dnl w11h r,,rht,2,,,., ,
nrrl- th.it rn,ll',1 thr hn~t. t)ll\ilm, h.micrs ind11dr thr ,kin whnr.1, other• rrq111r, rnor h,n<lm,t nf ,nt,~-.. 1.,, ''' ~.-,,., ,,,
anJ the mu,o~I mrmhr.11H·~. Thr alkl,ty of the ,1nnrnd1 wn it, dTn tor ,,,1< m. Ret1( 1111n• ht-twcrn c11m~nvnl m<~·, 11k•
tent~and of t't'r.-pirati,,n IXI-.CS a fmthcr hJrticr to 11q1.,mi,m~ 111 frt1~111rn1~ of lomrlrmtnt m<~crni(• .1n<l ,..rll1.1l.ft rt1..,p•,,n
un.iblr to p.mw in a,iJi, con llit,nm. 1-'mrml·~ ~ud1 a, triAArr all1\t1t1011 of HII, of tht mn,,~ Of ¥1,1r'~ imm 11 rw
ln,ozrn1e, whi,h i~ rrc"-·nt in lc,m, dtlad, the c~l1 w.1 l1, of ,cr- ,y,trm,. Hrlcnt ,tud,r, nn w ll« tiM 1n<l1<.1tt ttur rht~ P"o-
t.iin Nch·na on l'Ontact. The import.11Kr of thc:M: h,min~ hr- trin, m.i)· kill cl'rt,11n h,ftm.i d1m!ly tw d,~rnff 1n,l 'Mr hpd
comt'S ol,,ious when they are brca,hl,J. Rite~ of anim,tb or mrrnhrJnr, nr, altrrn.it1vrl}, t-,y •~rtt(,tlllni tht hotdu1.1 '"""
in~-...1s pun,1ure the skin anJ ,an introJu,r a number of dis- hJnce their su\Crptih1hty to ph.il(11Cyt<~
ea~ Animal bites can ,··ommuni,ate rabies or tc:tanus, MJny of the mol«u~ 1,m,"td m um.att smmunlfV ~ tht
whereas inse.."tS urry a host of dise,1ses, including malaria property of patttm m:ognition, tht ~,hry 1<1 rro 1tfl"' A ~
from mosquit~ plague from fleas, and Lyme disease from class of molccub. Bec.iu.1t cert.i,n typr, ,-,f mnkculn .,, ur...iq~
ti~ks. A dramati.: example of barrier loss is seen in burn vic- to microbes and never found in multiu.flul.u ~nt~'- rtwr
tims, who lose the protecth·e skin at the burn site and must be ability to immediately m:ognizt and comM ITTV..dm d1..pLwin~
treated aggressi,·ely ,,i th drugs to prevent bacterial and fungal such molecule; is a strong featurt of m~ immunitV. ¼~I.In
infection. Beyond the primary barriers, irmate immunity in- with pattern recognition ability rmy be soluble. bu Mf'qvT!Y
cludes a host of cells, such as the phagocytes demonstrated by and the complement components ~ribed .t,,,..,, or Ult'Y ITi.N
Metchnikoff, as well as antimicr obial compounds synthesized be cell-associated receptors, such a.s tho:w doign.atcd chc W-
by the host that can recognize and neutralize invaders based like receptors (TLRs), described in C~ptc!T l
on common molecular surface markers. Should the invading pathogen breach the~ ·s ~ .Kwf
chemical barriers, it may then be detected by pattern rccquu-
Phagocytic cells are a barrier to infection tion molecules of the host and taken up by ph.agucHa: ,;.da,
' causing the system to react with an inflammat~· re,pon.-.t , '!tt
An important innate defense mechanism is the ingestion of Chapters 3 and 13). This response conc,ntratcs demcnt.s .Im-
extracellular particulate material by phagocytosis. Phagocyto-· nate immunity at the inflammation sit, and m.iv rMt in the
sis is one type of endocytosis, the general term for the uptake
marshaling of a specific immune response against tht Lma..kr..
by a cell of material from its environment. In phagocytosis, a The specific response called upon by the infl.un~oon is tht
cell's plasma membrane expands around the particulate mate- adaptive (sometimes called acquired) immune mporuc.
rial, which may include whole pathogenic microorganisms. In contrast to the broad reactivity of the inn.He imm~ )-n.-
Most phagocytosis is conducted by specialized cells, such as tem, which is unifonn in all members of a spnies, th.: ~
blood monocytes, neutrophils, and tissue macrophages (see component, adaptive immunity, does not COITI( into pwv until
Chapter- 2). Most cell types are capable of other forms of there is a recognized antigenic challenge to the ~ m . ..\J.ip-
endocytosis, such as receptor-mediated endocytosis, in which tive immunity responds to the challenge .,,.;th a hi~ d(fJtt u,.·
extracellular molecules are internalized after binding to spe- specificity as well as the remarkable pro~rt)· of~mem1.1ry: T\'P-
cific cellular receptors, and pinocytosis, the p~ocess by which ically, there is an adaptive immune response .ig.unst .ID antigen
cells take up fluid from the surrounding medium along with within five or six days after the initi.il eX(X'ISure to th.it .mtigen.
any molecules contained in it. Future exposure to the same antigen results in a memorv ~
sponse: the immune response to the senm<l .:h.illenge O\Xurs
Soluble molecules contribute more quickly than the first, is stronger, ffl<l is often more ettl'\:-
to innate immunity tive in neutralizing and clearing the p,llhogen. The mJior .igents
of adaptive immunity are lymphoq1es anJ the antiboJ.ies the~
A variety of wluble factors contribute to innate immunity,
produce. Table l-3 compares inn.ite and .1,\Jptive immun.itv.
among them the protein ly~ozyme, the interferon proteins,
Because adaptive immune responses l\'(\Uirt some time tu
and components of the complement system (see Chapter 7).
marshal, innate immunity provides the first line uf dt'fenst
Lysozyme, a hydrolytic enzyme found in mucous secretions
during the critic.ti period _just alter the host's e:\posurc to a
and in tears, is able to cleave the peptidoglycan layer of the
pathogt•n. In genernl, most of the microorganisms en.:oun-
bacterial cell wall. Interferon comprises a group of proteins
tered by a healthy indiviJual are rec1dily dear«! within a few
produced by virus-infected cells. Among the many functions
days hy defens, mechanisms of the inn.ilt' in1111u1\e system ~
of the interferons is the ability to bind to nearby cdls and in-
fore they activate the adaptive immune system.
duce a generalized antiviral state.
Complement, examined in detail in Chapter 7, includes a
group of serum proteins that circulate in an inactive state. A Collaboration between innate and adaptive
variety of specific and nonspecific immunologic mechanisms
can convert the inactive forms of complement proteins into
immunity increases immune responsiveness
an active state with the ability to damage the membranes of
pathogenic organisms, , either destroying the pathogens or
It is important to appreciate that the innate and adaptive
immune systems do not ope,ate independently-the~
'\,
.;_
A,
!,
 f1l ,1Jl y a ll <l
,rotl'ifl \ I)II. 1d , pc<. I t n1olc<.U Ic~ Wll. h
k11cm11 .,~ ,1d,1pt11r I r more diffl' rcn h 1,wc thcr
\ Hlllllt ,1111·t111sI>. to two " hw,iy, hrir1~ . 1·n" t cm n
r,
n,lr, in th e ~i~ 11 ,ilt 11 ~ p,it t . eel , c.tiv it y.
1
,rnd p111111nt111 ti ·1r cortl ,111
g ll f ,v!I withm tr1 e
. '
d the gene
.,,~no/ 1ncpti1111 i1f1,•11 /fa ~.,10 rnol n .: ul eraor ion
that can_
l1m1tf'd •nd
fo:e<j H1Rhl'f d1ve,se,
;,:II
of,, "sc,011d 111c55CIIK"'• a II and 5tim ul ate mcta
~olJC
improves du, mg the diffu se to oth er -~11. e~ · the ce
,n . uc·leo tidcs (c AMP cGMJJ )
cours e of immune di.in >\l'~- Exa mple s arc l·yc 11c nbran e phos r ·d'
pho ,p, .
'
R•~to re,po n,e c.1kiu111 inn (Ca1 • ), ~nd mem I (DAG )
~ "'t.ct,on IO(>nttcat to and inos itol
Pnmary ... !of>On~ Mum more rapid than Jniva t1 vcs ~uch as d1acylglyce ro
Majo r c ~ t s pnma!)' respo n\t triph o!,ph ,, tc ( IP_/
8.al'Tlffl (, .g .. skin)· diva ted or
. f,osp
phag ocyte s; . lymp hocy tes;
■ Prvtcin ki11ascs and protelfl P hhata ses are a
phor ylati on of targe t
patt, m recognition ant igen- specific .
mole cules recep tors; antibodies i11/ribitccl. K1na
. , the P os ·ne) of key s1gn
scs ca 1aJyzc ·
a
I
. e orthr eon1
residues (~yrosine, ~enn , os hatases catal
yze
transduction proteins. Ph . P h ffect of
fun ..tion as a high l .. k.inases. Thes e
d . . . dephosphorylation, reversm~ t e e ·gnal
U.."1.ng a com bine d~res
coul d rrod uce by .t r~se
tnter actw e and .
: 0 operat1ve system, pro-
m~re effective than either bran
mun e com pon en~ sel · _ertam cellu
lar and mole cular im-
ch
enzymes play essent1a

. b
. l oles m man y s1
r
pathways of immunological interest.
tran sduc tion

.
imm unit y. p ay unpo rtan t roles in both types of ■ Signals are amplified r enzyme cascades. An enzy ny
me m a
signaling pathway, once ac t'vat
1 ed cata Iyzes ma
An exam ple of · .
'
additional reactions. The enzyme may gene
~ -een mac r h 000 perat.1on ts seen in the encounter rate man y
tors op ages and micr obes . Inter actio ns betw molecules of the next com pone nt in th e pa th
cep een re- . ate way or
sol ble on mac roph aaes and . b'al activ many copie .s f h
o t e ne xt enzy me in the sequ ence .
prot ems that ~stim ul nucr od di com pone nts generate
- I
u This greatly amplifies the signal at each st
ate an rect adaptive. . ep a~d offer s
resp onse s, f.acilitating the parti cipa tion tmm une oppo rtuni ties to modulate the inten sity of
mun e S\'Stem in th lim. of the adap tive im- a signa l.
. . ee mati.on of the pathogen. The soluble These processes are schematically represente
prot eins are gmw th facto r-lik e molecules d in Figu re 1-6.
eral. nam e .--nkines. Th know n by the gen- The activity that results from signal trans
-, - e cytokines react with . recep duct ion may be
tors on synthesi°s and/ or secretion of certain prote
vari ous cell type s and signa l the cell to ins, diffe renti ation ,
perfo rm functions such or the initiation or cessation of specific func
as S)nthesis of new f.actors or to unde tions. For exam ple,
rgo differentiation to a stimulated macrophages secrete cytokines that
new cell type . A restr icted class of cyto can direc t adap -
kines have chemotactic tive imm une responses of lymp hocy tes
activ ity and recru it specific cells to the agai nst spec ific
site of the cell secreting pathogens.
that cyto kine ; thes e are called chem okin es.
The type of intra cellu lar com mun icati In a complementary fashion, the adaptive
on mediated by cy- imm une system
toki nes is referre d to by the general term produces signals and components that incre
ase the effective:.
signa ling. Basically, ness of innate responses. Some T cells, whe
sign aling involves the reac tion betw een n they enco unte r
a soluble molecule ap~ropfiately_ presented antigen, synthesize
(liga nd) and a cell mem bran e-bo und and secrete cy-
molecule (receptor) or to~ es that mcrease ~e ability of macr
betw een mem bran e-bo und mole cules ophages to kill the
on two different cells. microbes they have mgested. Also, antib
The inter actio n betw een a rece ptor odie s prod uced
and its ligand leads to against an invader bind to the pathogen, mark
meta boli c adap tatio ns in cells. Ther e are ing it as a target
an enor mou s num - for ~ttack by macrophages or by com plem
ber of diffe rent signa l trans duct ion pathw ent prote ins and
ays, all exhibiting servmg as a potent activator of the attack.
com mon them es typic al of these integ
rative processes: . A _mahjor di~fe~ence between adaptive and
inna te imm u-
■ Sign al tran sduc tion begins when nity
a signal binds to its . . 1s t e rap1d.1ty. of the innate imm une respo
receptor. Rece ptor s may be insid e or outs 1
utt 1zes a preexisting but limited repert nse, w h'1c h
ide the cell. . f
Sign als that cann ot pene trate the cell
d . .
compobne~ts. A__apt1ve imm unity comp ensa 01re o resp ondi.ng
mem bran e bind to tes for its slow er
rece ptor s on the cell surfa ce. This grou onset y its ability to recognize a mu h
p includes water- ~ · .d .
solu ble sign aling mole cule s and mem ore,gn su bstances and also by its ab 'I't c w1 er repe rtoir e of
bran e-bo und . .
11 Y to impr ove duri.
ligan ds (MH C-pe ptid e com plex es,_for a response, whereas innat e imm unit ng
exam~le). .
Hyd roph obic sign als, such as stero ids, Y remains cons tant.
c.an diffuse
thro ugh the cell mem bran e and are boun
d by Adaptive imm unit y is highly specific
intra cellu lar rece ptor s.
Adaptive imm unity is capable of . .
. nal tran sduc tion pathways involve the signa eliminating specific foreign m. recogn'.zin
Man y s1g l- g and selectively
& bl ,fpat hwa y components. Molecules (i.e., foreign antigens). Unlikeicroo rgan1sms d
indu ced asse m Y 0 . . an mo Iecules
innate imm une
responses,
 nvuv11w ,,, ,.,, 11-1M11~~, \f\fl M 11
,
~■ OVERV1tw FIGURE , 6: Common Themes in Signal Transduction

Signal reception

S,"nahng PAlhw11y1
are ,n,1t111t"d when 1
s,gnel binds il s receptor

r~..,
Transduction

2 r------- ------,
Ligand binding to
receptor induces ;I.Y~
I: " I
assembly of signaling
pathway components ~

Signal-mediated
generation of Adaptor protein binds Additional
docking site protein(sJ bind

31----- -------- ,
Generation of second
messenger carries
signal to cell interior

P ~ Activation of
Second pathway
messenger components

41----- -------- ,
Phosphorylati on/
dephosphoryl ation

-
cycles under control
of the signaling
pathway activate/ ATP ADP
deactivate additional
pathway components

Phosphatase

5>--- - - - - - - - - ,

TuTu ~ ~
Enzyme cascades ~ May be hundreds or
amplify the signal,
converting molecules
to their active forms
~:~•,:~:,'""';on,

•••• •••• •
Metabolic effectors
 1~1 Al )()l ll 1ti 'N
i/f recognition. The
•d,lpti, (' ~ f sdf-rtvnse 1
• ·• cJl1,11>le O . . ui ~h self from non.
hut
. "ft' I\'•· '''
·t
11
'l·, ,It\• 1111t 1lw , 11 . - · 11 111,,1 11 1~
1111 11t ,11'"" • ~y~tcrn to
d1 ~nng · .
Jes is essential. As
ltnn,un . \ "'"' In \I' .. • llt· 111 ,111 lllt' ll11'1 ·r, nf ,I ,pn ii'~ .
. . r 1he 11111r111nc · If molec u
"". \1 i~,, l,I\"'). "''"· \\I '"\ 11 111 ·~\'Ill\ d,.,lh ll){l' \ , t\tl,,pl lvt' ~ Ill 1,1 y o I on ly to nnn ~e. . Ji,ti nguish self from
• .l . \ 1,11 ,hln 1 ~!'If and rr~prHll . e of 1hc abilit y to self compo
l'\lll1~l' llh. \ .. ,, I\ .\11 11h11tr, : dc~l rilled 111:lnw, f,11 IL_ir priate re~pon.~e to
· l"-"- 1hut" -
11 ,;rppro
" ni,,-r,11v . non~clf lct1d~ 10 an
lll'lll ~ ;Ill( I l••
'"'' hr fa tal.
" lm1nunnh, ' . .
• I.': ••
!,:I\ lll<'11'\ll )' ti en-presenting cells
,~lf-nnn ~df . .. Lymphocytes and ~n ?mmunity
l't\:t1 gnrt llll\
The •ntiocni .
ftt: · · l' \: S(lt\:1fkit Of I
. coopera te in adaptive ' . Ives two major groups of
n~llts II to distino .. Y t le ad..rptivr immune sy~ll'ITI onse invo
Anti~x1 IC.-S- l..'.ln di).t'r,llls,1l . subtk lrn An effective immune res P . · esenting cells. Lymphocytes
I ncnrcs among antigl'ns. d antigen-pr d·
that l f1fl"1er in
· onlv a' rn~u1sh hl'l\\l\."l I\ two prokm . molcniks cdls: /y111phocytes an h' bl od cells produce m the
_• s of w rte O • •
c.i1,abl e of genrra. tinsmg1e amino a\-·d 1 · 1·11c immune
. are one of many type f hematopo1es1s (see Chap-
systrm is the process o . .
mol cxu · les, allo\\ino g• treml'ndous· 1J'11 •ers,ty · .m its
. re1:ognition bone marrow bY the bone marrow, circulate m the
ter 2). Lymphocytes leave d reside in various lym-
tu
res on foreign ant'~ it to fCX(wn ·· b'II
. 0 ize ' of unique struc-
I ions
h fIc systems, an .
te
rn recognition m .' ,gens Th,s ·1bTt 11 · · blo~d an d Iymp a roduce and display ant1gen-
• Yism contrast to the pat- th
recognize broad cl· o1ecu 1es of the innate system, which pho1d organs. Because ey P ho es mediate the
st ructures present assesh of orga msms · based on molecular binding cell surface receptorS, lymp
. .
'1:
. d' .
. attributes of spec1 6city, 1vers1ty,
· on t em The ad · defining 1mmuno1og1c · · The two maJor . popu
mze a single hm,, f .· aptive system can recog- memory and self-nonself recogmtion.
'th minor ., r o organism and d'"' . among -
"1 gene..; . . 111
erent1ate those . ' I hocytes (B cells) and T
uC Va.nations. lat1ons of lymphocytes-8 ymp . .
Once the adaptive imm lymphocytes (T cells)-are described briefly here and m
sponded to an ant· . une syS tem has recognized and re-
is, a second 1gen ' exh1·b its
It · immunologic
· memory- that greater detail in later chapters.
encounter with th . ,
heightened state of im e ~a_me antigen induces a
tribute th · mune reactivity. Because of this at- B Lymphocytes
many ·• c e immune
. system can con1er c 1.
1felong immunity to Blymphocytes mature in the bone marrow; on release, each
· m1ect1ous agents aft . . 'al
er an imtJ encounter. Finally the expresses a unique antigen-binding receptor on its mem-
munune system normall Yrespon ds only to foreign antigens, ' brane (Figure 1-7). This antigen-binding or B-cell receptor

(a) 8 cell (b)

J Surface antibody Soluble antibody

Antiget>
binding
receptor
/a=
~~ !/\
(antibody)

ffiWffi ~ ~
~M~
Plasma
membrane
FIGURE 1-7 B cell (a) The surfaces of B cells host about 105 (secreted} antibody showing the hea ch .
molecules of membrane-bound antibody per cell AU the antibody (red}. Note that the soluble form lac~ ams (blue) and light chains
the
molecules on a given B cell have the same antigenic specificity and cell membrane. (The ovals in th d. sequences that bind tht
. e 1agrams rfl>tV
can interact directly with antigen. {b) Membrane-bound and soluble protein folds called lg domains d. . ~,,.esent ch¥.aer1st,c
• ISCUSsed 1t1 Chapter 4.)
 ovr II.VII w or Tttr IMMIIN( \ yrn M
1J

A11ll"1·n
prt'~t·n1 lrtl(
tdl ~

MIil . l'ln~~ II

- • Anllt4t'll
prcSt'llll'll hr
MIIC rnolcrulr

( CD4 TCR CDS TCR

~ ~ffi ~ ~ T-cell plasma

~ ~™ MMW membranes
T helper (fH) cells T cytotoxic (fc) cells

FIGURE 1-8 T cells. Key to the function of T cells is an antigen- only antigen associated with class I MHC molecules. Both types of
binding molecule, the T-cell receptor (TCR). In general, Tcells bearing T cells express about 105 identical molecules of the antigen-binding
CD4 (CD4 ~ cells) act as (a) helper cells and cos+ cells act as (b) cy- T-cell receptor per cell, all with the same antigenic specificity. (~
totoxic cells. (c) co4+ cells recognize only antigen bound to class II ovals in the diagrams represent characteristic protein folds. discussed
MHC molecules on antigen-presenting cells. cos+ cells recognize in Chapter 4.)

is a membrane-bound antibody molecule (Figure l-7b, c). T Lymphocytes

Antibodies are glycoproteins that consist of two identical T lymphocytes also arise in the bone marrow. Unlike B cl'lls,
polypeptides called the heavy chains and two shorter, i~e~- which mature in the marrow, T cells migrate to the thynms
tical polypeptides called the light chains. Each heavy cham 1s gland to mature. Maturing T cells express a unique antigen-
joined to a light chain by disulfide bonds, an_d_ the binding molecule, the T-cell receptor (TCR), on their mem-
heavy/light chain pain are linked together by add1t10nal branes. There are two well-defined subpopulations of T cells:
disulfide bonds. The amino-terminal ends of the pairs of T helper (TH) and T cytotoxic (Tc) cells. T helper (Fig-
heavy and light chains form a site to which antigen binds. ure 1-Sa) and T cytotoxic (Figure l-8h) cells can be distin-
When a naive 8 cell (one that has not previously encoun- guished from one another by the presence of either CD4 or
tered antigen) first encounters the antigen that matches its CDS membrane glycoproteins on their surfaces. T cells dis-
membrane-bound antibody, the binding of the antigen to playing CD4 generally function as TH cells, where.is thlise llis-
the antibody causes the cell to divide rapidly; its progeny dif- playing CDS generally function as Tr cdls (see Ch.ipter 2). A
ferentiate into memory B cells and effector B cells called recently characterized third type of T cdl, called " T ngula-
plasma cells. Memory 8 cells have a longer life span than tory (T rq) cell, carries CD4 on its surface hut m.iy be distin-
naive cells, and they express the same membrane-bound an- guished from TH and Tc cells by cell surfa~·e m.irkers
tibody as their parent 8 cell. Plasma cells produce the anti- associated with its stage of activation.
body in a form that can be secreted (Figure I -7b, right) and Unlike membrane-bound antibodies on B cells, which
have little or no membrane-bound antibody. Although recognize free antigen, most T-cell receptors can recognize
plasma cells live for only a few days, they secrete enormous only antigen that is bound to cell membrane proteins called
amounts of antibody during this time. A single plasma cell major histocompatibility complex (MHC) molecules.
c,m secrete hundreds to thousands of molecules of antibody MHC molecules are polymorphic (genetically diverse)
per s~cond. Secreted antibodies are the major effector glycoproteins found on cell membranes (see Chapter 8). There
moli.'cub of humoral immunity.
clrt' " '\)
I 1 lll,1 1,1r I1
nol'(U) 1'n 11f \II .,
\ ti-_ 1,h,,h h "'"'"' ,,1,, , L," I \II I(
'C'rkhr
Pt\'). t
.Ill' 'I"-, ,,,,
.. ~"\. l'Hh h, • 111 ·
\ , ht"l .
"
.1,\. ,., 1'", I 1

•~,-r,
I
'
...., ,, 111 ·" I, !\II 11lh lt-.,ti d \' 11, Pl
.1111 \ I h\ 11 \ I
,~, 111111
I h 111,•h "'"· 1d11, h .Ill ti
.
w• .'
• I
'
.. i .

' " ll.t1w l •11 , 1 ~"' "' (,\I'( ,1 1I 1p11r I II, l

·)
-I
nlol ~u,'ona(·
11 k'm,,n· T l°'"ll
.
.\ ti.,-r " T . ·I
~tJ--1 ~
d''l 1h, n,-
1
n11nt '·1' ·111 ' 11:,n .. ,111h111,d111th,1\ 111(
· l .,rll 1'r.ihtn ,lie, .111.t ,li1l.-1rnt1.11r, mtti
' ~ .in,1 , .1n
Ii " I r,,,, ,p,1 1 .,
,,u, (I l,, l11t l ,di\.
I
,.
..
, '
\

' 1(_ d.i'-' 11 I l .llh lllh'l,ld, with ,Ill ,lllll~fll -

c.:,c'1:<X'~
J
a m "I 1"l' , ,. uk ''- ' 111 1'I,·, . IIW u·II ".,, ti, .,tnl - it 1111
Yarinus l°'Yhi'I.. ·
<.' • '''1I(. Ir •111'1 1111 1 ·
1.1111111 ,rn,1 hq:111~ 11, ,,-,1rt(
Ill<.'~. l he ,,'\:t\'I • I .1 11
1\1Ie in a.:ti,·.1, · . · . '' l h 11.111r, pl.11· ,11 1 i1111'1Ht,111t
8 , dh l . ·ll .
oth<.'r cells th t Inf. .. ·' ,· u ~. 111,1, r,,I' I1,1it,·~. ,111d , .1111n1 ,
· .i p,lrh(tpate · ti ·
en.:-cs in th Ill ic immum- rr~p,m~l'. I>itkr-
e '"res nf C\t 1,. m,·s ·
1'r11d11\',,J hy .id iv.11\'d T11
cells result · d' .: · ''
• _m 1lkrcnt
. "Jtt nns of 1mnnm1·
, • n·~p,m~l'. One
""' - 'LJ
r v~ll• e re~punse IS th. . l . .
r
.
fio . ~ llluud i,m of J 1'.' hJtWl' m T . cl'lls to ·• f an antigen-prHentina
rm C\1otoxic T 1 h c- 1
killin · . )'mp ocytes (CTLs) th.11 exhibit n·ll- .,,;,,ograph O hocyte {From A. 5.
S or. ntotox1C a(ti\'1·1,·. · CTLs hJ\'t' a v1t.1l . fund1011 . 111 . FIGURE 1-9 Electron . . with a T 1yrnp . .
· ·
moni tonn~'. the cell s Of the body and eliminating any th,,t ( . ht) associating . p t and Future. Academic
_ rig ,-1tos1s- as
d 1.~r 1a,· anti 0 en su ·h · ·
macrophage
B2 in Phago...r
• _ t- • 1. as v1rus-111fel'.'ted (ells, tumor cells, and Rosenthal et al., 19 '
cells of a toreign tissue gr.1ft. Press. p. 239./

. S}'stem is at work in
Antigen-presenting cells interact with T cells h O
f the unmune
and their subsequent
The humoral branc . •
. f B ll with antigen . .
Acti\'ation of both the humoral and cell-~ediated branches the interacuon o ce s . . . to antibody-secreting
d'ffi ent1at10n in
of the ~mune _system requires cytokines produced by TH proliferation an d 1 er 'b d functions as the effector
0
celh. It IS essential that activation of TH cells themselves be plasma cells (Figure l-lO). :.t~. ~o antigen and facilitating
1 1
carefully regulated, because a T-cell response directed of the hum oral resp~nse by ; ?Ji tibody is eliminated in
against self components can have fatal autoimmune conse- its elimination. Antigen coate ~ dan an cross-link several
quences. One safeguard against unregulated activation of TH several ways. For example, anti o y c dil in ested bv
celh is that the antigen receptors of TH cells can recognize antigens, forming clusters that are more rea . y g :
only antigen that is displayed together with class II MHC phagocytic cells. Binding of antibody to ant.Jgen on a mt-
molecules on the surface of antigen-presenting cells. These croorgan1sm. can also actlV . complement
· ate the • . result-
. . svstem, ,
specialized cells, which include macrophages, B lympho- ing in lysis of the foreign organism. In a~dinon, anll~} can
cytes, and dendritic cells, are distinguished by two proper- neutralize toxins or viral particles by coatmg them, which pre-
ties: ( 1) they express class II MHC molecules oh their vents them from binding to host cells.
membranes, and (2) they can produce cytokines that cause Effector T cells generated in response to antigen are re-
T fl cells to become_ activated. . . . . sponsible for cell-mediated immunity (see Figure 1-10). Both
\ Antigen-presentmg cells_ first mternah~ antigen, by either activated TH cells and cytotoxic T lymphocytes serve as eff«-
phagocytosis or endocytos1s, and then display a part of _that tor cells in cell-mediated immune reactions. C}1okines se-
antigen on their membrane bound to a cJass II MHC molecule. creted by- TH cells can activate various phagoq1ic cells,
The T cell interacts with the an'tigen-dass II MHC molecule enabling them to phagocytose and kill microorganisms more
compl~x on the membrane of the antigen-presenting cell effectively. This type of cell-mediatro immunt> responSt> is es-
(Figure 1-9). The antigen-presenting cell then pro_duces an pecially important in ridding the host of bacteria and proto-
additional signal leading to activation of the TH c) zoa cont_ained_ by infected host cells. CTL.s participate in
~ell-m~d1at~d 111:1mune reactions by killing altered self cells,
mclud111g v1rus-mfocted cells and tumor cells.
Humoral and cellular immune responses
exhibit different effector functions The antigen receptors of Band
As mentioned earlier, immune responses can be di~ided i~to T lymphocytes are diverse
nd cell-mediated responses. Humoral immunity
h umor al a d · nune in-
'ty that can be conferre on a nonmu The antigenic specificity of each B cell • d . •
. b b . is ett>rmmed by the
refers to immum_ . . . f serum antibodies from an im- mem rane- ound anligen-binding r .
. 'd al by adn11mstrat1on o be expressed by the cell. As a B II ece~tor (i.e., antibody)
d 1v1 u t ell-mediated immunity can ce matures m the bo
. d" 1·dual In contras, c its specificity is created by random ne marrow,
mune in 1v · . . t' n ofT cells from an immune . f rearrangements f
c d only by adm1mstra 10 nes o gene segments that encod h . o a se-
tr .1ni.1erre
e t e antibody molecule
iudiviJuaL
 1
OV[RVl [ W OF TH [ IMMUNESYSTEM CH A P T f R 1 15

\&._• OVERVIEW FIGURE 1-10: The Hu moral and Cell-Mediated

--- .. ------ ..... ------ -- --- ----- --·
Branches of the Immune System
~
--
- - - ...... --- --- . -- - -.. ---- -- -.. - -- ------------- ---.. --- - - - -- --.. --

A11tl~ens

roreittn Viruses Bacteria Parasites Fungi

prott'ins

lntemallzed ant igen

digested by cell

2------ -------- '\

Alt_e red self cell I
pr~ents antigen I
I

""
Oass 1----
MHC

3-------~
T-cell receptors
recognize antigen bound
to MHC molecules

Activat('d 1 6-----~
T Activated CTl..s
4-------- recognize and kill
Binding antigen-MHC altered self cells
activates T cells

i . . \ Cytotoxic T lymphoeyte (CTI.)

•• ·i ••
J, • \, 51------------',
/
•••
c~U-mcdJatcd rapoDK
Activated TH cell secretes
g 1okines that contribute to
activation of B cells, Tc cells,
Humonl respome and other cells

Antigen

"' 1----- - -- - - - - , 81-----------,

Bed 8 rclh inter.Kt 'I\ llh .ulllKen ~ Anrih(xh bind~ anuken
and 1.btteren11,11e into plasma L~lls and lacilllJlt', it, dt',lr.lOC('
.lnllbtxh ·-.t'l'rt'ling pLIMlU t·eU~ from the bod)

In the humoral respon~ . Bcells interact with ant;gen and then dif- cells recognize antigen presented on self cells. TH cells respond to
tffentiite into antibody-secreting plasma cells. The secreted anti- antigen by producing cytokines. Tc cells respond to antigen by de-
body b11~ to the ant,gen and facilitates its dearance from the veloping into cytotoxicT lymphocytes (CTLs), which mediate killing
bod) In the cell-med,ated response, various subpopulat ions ofT of altered self cells (e.g., virus-infected cells).
 16
INTRODUCTION

. cell
1 If
Anti)(l'llil
' 1wp1idr

ft l l;1,~ I
~ ~111(

6 l la).~ 11
U .,me
v T-~·d l
,l /41~r.."1" ~ /!: -O
1,~~~
l't'\.'c-pt or
TH celJ
) CD8

ting cell
Antigen-presen
CD4 Viru~-infn·tc u cell
function as T helper
le genera lly .
displayed with a class II MH~ rn~~ec:ntigenic peptides displayed wrth
FIGURE 1-11 The role of MHC molecules in antigen recogni- (T ) cells.T cells that recognrze o y ction as T cytotoxic (Tc) cells.
tion by T cells. Class I MHC molecules are expressed on nearly all nu- a ~ass I MHC molecule generally fun
cleated cells. Class 11 MHC molecules are expressed only on
antigen-presenting cells.T cells that recognize only antigenic peptides

. . t O tissue transplan tation. Mis-

(see Chapter 5). At maturity, each B cell possesses a single gained attent10n as a barner • t" n of transplan ted tis-
functional gene encoding the antibody heavy chain and a matched MHC genes lead to r~JeC JO me his to- ( tissue)
sue and organs. Hence t e na .
single functional gene encoding the antibody light chain. All the MHC en_code two maJor
compatibility. Loci within
antibody molecules on a given B lymphocyte have identical
classes of membrane-bound glycoprotems: class I and
specificity, giving each B lymRhocyte, and the clone of
class II MHC molecules. As noted above, TH cells generally
daughter cells to which it gives rise, a distinct specificity for
a single antigen. The mature B lymphocyte is therefore said
recognize antigen combined with class II molecules ,
to be antigenically committed. whereas Tc cells generally recognize antigen combined
The random gene rearrangements during B-cell matura- with class I molecules (Figure 1-11 ). MHC molecules func-
tion in the bone marrow generate an enormous number of tion as antigen-recognition molecules, but they do not pos-
different antigenic specificities. The resulting B-cell popula- sess the fine specificity for antigen character istic of
tion, which consists of individual B cells each expressing a antibodies and T-cell receptors. Rather, each MHC
unique antibody, is estimated to exhibit collectively more molecule ~an bind to a spectrum of antigenic peptides
than 10 10 different antigenic specificities. A selection process mostly derived from the degradation of protein molecules.
in the bone marrow eliminates any B cells with membrane- In both class I and class II MHC molecules, th ere 1s . l ft
· h' h' h ace
bound antibody that recognizes self components. (This pro- wit m w ic the antigenic
.
peptide sits and . d
1s presente to
cess is discussed in detail in Chapter 11.) The selection T 1ymp hocytes (see Figure 1-11).
process helps to ensure that self-reactive antibodies (auto-
antibodies) are not propagated. Antigen selection of lym h
The attributes of specificity and diversity also characterize clonal expansion P ocytes causes
the antigen-binding T-cell receptor on T cells. As in B-cell
maturation, the process of T-cell maturation includes random A ma~re immunocompetent animal .
rearrangements of a series of gene segments that encode the of antigen-reactive clones 0 f T contams a large number
cell's antigen-binding receptor (see Chapter 9). Each T lym- gemc · of each of th and B lvm
· spec1'fi city , ...p hocytes; the anti-
phocyte cell expresses about 10s receptors, all with identical specificity of the antigen-b· d~se clones is determined by the
specificity for antigen. The random rearrangement of the TCR of the clone's lymphocytes m tng receptor o~ the memb
genes is capable of generating on the order of I0~ unique anti- each T and B lym ho · ~ noted above, .the. . . rane
'w'th · b p cyte is deter · -- ~~~diq_ty of
genic specificities. I antigen y random llllned before .
tion in the th gene rearrange Its contact
ymus or bon ments dur·
The role of . e marrow. \ mg matura-
The major histocori:1pat_ibility ~omplex . antigen beco
with and activates mature a mes critical h
molecules bind antigenic peptides 1 t' w en it .
ymphocytes, bringin ab • n 1genical1X co . interacts
· hi'stocompatibility complex is a large genetic cell£ with' .t given a:ti o~(~xpans io9 of mm1tted T and B
The maJor . . th e Population of
'th multiple loci. This group of genes first clonal selection an ~enic specificit"
comp 1ex w1 ' antigen b'Inds to a ,. 1n. th·is Process of

'
•
Particular T or B ceU
 7
OV[RVllW OF THE IMMUN[ SYSHM 17

Ront"num1w Pcrlphcr-AI lr mph11id ,1~~,ic

Maruration into mature Antigen-dependent proliferation and

antigenetically committed B cells differentiation into plasma and memory cells

FIGURE 1-12 Maturation and clonal selection of B lympho- a clone of memory Bcells and effector Bcells, called plasma cells; all
cytes. Maturation, which occurs in the absence of antigen, produ~e~ cells in the expanded clone are specific for the original antigen. The
~ antigenically committed B_cells, ea~h ~f_which expresses antibody plasma cells secrete antibody reactive with the activating antigen.
with a single antigenic specificity (indicated by 1, 2, 3, and 4). ~al Similar processes take place in the T-lymphocyte population, resulting
se~n occurs when an antigen binds to a Bcell whose membrane- in clones of memory T cells and effector T cells; the latter include ac-
bound antibody molecules are specific for that antigen. C).anal~Q_an- tivated TH cells, which secrete cytokines, and cytotoxic T lymphocytes
sion of an antigen-activated Bcell (number 2 in this example) leads to (CTls}.
,--- -

(y
and stimulates it to divide repeatedly into a clone of cells Immunologic memory is another consequence of clonal
with the same antigenic specificity as the original parent cell selection.DuringcfonaI selection, the number of lympho-
(Figure l-12). cytes specific for a given antigen is greatly amplified.
Cl~al selection PJ:Qvides a framework for understanding Moreover, many of these lymphocytes, referred to as memory
the sptcificitr and ~ n_seJf _rec~8!!i_tign_that is characteris- cells, have a longer life span than the naive lymphocytes from
tic of adaptive immunity( Specificity is present because only which they arise. The initial encounter of a naive immuno-
lymphocytes whose receptors are specific for a given antigen competent lymphocyte with an antigen induces a primary
will be donally expanded and thus mobilized for an immune response; a later contact of the host with antigen will induce
response~Self-nonself discrimination is accomplished by the a more rapid and heightened secondary response. The am-
elimination, during development, of lymphocytes bearing plified population of memory cells accounts for the rapidity
self-reactive receptors or by the functional suppression of and intensity that distinguishes a secondary response from the
the~ ,dis if they reach maturity. primary response.
 p A I\ T
INTRO DUCT ION
...
·rnarY a,, d seco ndar y re.
f ences
•,n the pn ) refle ct the phe-
Atu~c..-n RE 1- 13 Dif er. pons e
A Anlii,t t·n A FIGU (hurn oral res n animal is injected
'.',cn111d.1n• d nt1gen When a
+ spons

l
,11\11)-\l' tl 1' e to lnjecte a l gic rnernorY• ,.,., antibody response of
,11111-,\ I rnuno O
nomenon o f m
· ry seru,,,
l'rllll,I IT d es a pnma bout 10 to 17 days. A
anti II with an antigen, •t, pro rtucduration, pea k'in g at aults
. d nd sho in a secondary re-
Prin1.111 .1 n1i-A low rnagn 1tu ea . ·th the same an t'gen
1 . res
time (2- 7 days ), and
n·~t""m~e . izat1on w1 ks in less
second 1rnrnun . magnitude, pea . ry response. Compare
· greater 1n
sponse that is nths to years) than t he . pnma the primary response to
lasts longedr (rn~esponse to antigen A _w1t(~ight blue
the secon ary shading).
d the same mice
antigen B administere to
0
14
1-1
Time:. d.1y s

_ In the hum oral bran ch of the imm une ts or misd irect s its ac-
system, antigen a deficiency, and some times it over
d
reac
bilita ting
.
disea se, or even
indu ces the clon al proli ferat ion of B lymp hocy . d' comf ort, e
tes into anti- tivit1es to cause is on mani festa t10n. f·
s o imm
body -secr eting plasm a cells and mem ory B
cells. As seen in death. T~~re are several com m une
Figu re 1-13 , the prim ary respo nse has a lag of
approximately dysfunction:
5 to 7 days befo re antib ody levels start to rise.
This lag is the
time requ ired for activ ation of naive B cells • Allergies and asthm a
by antigen and
T H cells and for the subs eque nt proli ferat ion • Graft rejection and graft -vers us-h ost disea
and differenti- se
ation of the activ ated B cells into plasm a cells.
Antib ody lev- • Auto imm une disease
els peak in the prim ary respo nse at abou t day
14 and then
begi n to drop off as the plasm a cells begin to • Imm unod efici ency
die. In the sec-
onda ry respo nse, the lag is muc h short er (only
1-2 days), an- Allergies and asthm a are results of inap prop riate
tibod y level s are muc h highe r, and they are imm une
susta ined for responses, often to comm on antig ens such as
muc h long er. The seco ndar y respo nse reflec plan t polle n,
ts the activity of food, or animal dander. The possi bility that certa
the clon ally expa nded popu latio n of mem ory in subs tance s
B cells. These induced increased sensitivity (hyp ersen sitivi ty)
mem ory cells resp ond to the antig en more rathe r than
rapidly than protection was recognized in abou t 1902 by
naiv e B cells; in addi tion, beca use there are Char les Rich et,
many _more who attempted to imm unize dogs again st the
mem ory cells than there were naive B cells toxin s of a type
for the pnm ary of jellyfish, Physalia. He and his colle ague Paul
resp onse , more plasm a cells are gene rated in Port ier ob-
the secon dary served that dogs exposed to suble thal dose s of the
respo nse, and antib ody levels are cons eque ntly toxin react ed
100- to 1000-
a~os t instantly, and fatally, to subs eque nt
fold high er. chall enge with
In the cell- medi ated bran ch of the imm une mmu te amou nts of the toxin. Richet conc lude d
syst~m, the that a succe ss-
reco nitio n of an antig en-M HC comp lex b!
a ~pec1fic ~a- . immunization or vaccination results phy Iaxis,
ful m· . or
gT I t10n, whereas the opposite result may occu prote c-
h
ture ymp oc yte ,·nduces clona l pro_liferation mto vano us
) d · hi h
w c exposure to antig en can resul t in r--a nap h I .
y ax:is .
--m
T cells with effec tor func tions (TH cells and · · · th . ll I ha.I
CTLs an mto
A r
mem ory T ce 11 s. .ru "th hum oral imm une responses, sec- sens1t1v1ty to e antigen if the expo s
· d h . . a pote ntia y et ·
w1 h ure is
ceive t e Nobel pnze in 1913 for h' d" repe ated Rich et re-
onda ry cell- medi ated respo nses are faster and ·
stron ger t an phylactic response. is iscov ery of the ana-
prim ary. Fortunately, most allergic re t' .
rap1'di y 1ata
'" I. A speci
fic allergi _ ac ions in hu man s are not
.
a11 y mvo Ives a type of antib odc or .anap
II hyla ct IC ·
resp onse usu-
i~m un ~-D-ysfunction and Its uli11 £). Binding of lvE to _Yt ca ed_ lgE (for
immunoglob-
re 1eases substances thato cau , I s. speci
. .
fic
antig
.
Consequences . se en (alle rgen )
. . . . Wh en an aIIergic individual · irrita tion an d infla .
mma tion.
. te and adap tive 1mmun1ty dt:.- .
The abov e overv1c . ·w O f mna toms may mclu<le sn1:ezin is expo wh
sed to
. an aller gen, symp -
. . . -t ·ve system that protects the
pone nt mterac.: ?rcat hing (asthma); dermati~~ or s~~zmg, and
Pl.cts a mu I ucom. by pat h ogcn s that cause mfec
I . . . d' , diffi culty in
tious is- 111 more
host from inva swn d lls that can repro duce , . . . b extre
.
me cases st
. , rang ~n erup tions (hive s)· d
ulati o d
in an unco n- airways y mtla mma tion (F· n ue , an ,
eas es and from alterausee ce r This overview woul d not be
canc e •
of our health resources is igure 1-14 ). A signitofica blo k f
troll ed man ner to c · .f . tcfrag e_ o
. ing that the imm une system ~an, mg rom a 11 erg1es and asthexpe nded tO care n actio n
for th
ose su f",er-
m Iete with out men u?n im ruper ly. Some ·
times the im- ast h ma m t he United St t ma. The frequ ency
cod ~oes at time s, func tion th~ host adeq uatel f II
an y because of t h e most comm on reasoa es tplaces th ese com O a ergy and
fails to prote ct ns or a visit to I -
mun e syste m p amts amo ng
th e
doct or's offic e
 OV[RVllW OI TH£1MMLJN£SVST!M ' ' • £;,
[. ' '( A,u
1~ ~_,. ~
I. M11rr,1y Wf'f(' .1w,mlnl N11hd rrl/ C\ 111( ,1,h}h,(\ in Tr-1n \--
\, ...._ ......, _., ✓
pl,1111.itinn immunit y. l>rveloprnrnl 111 ~nlc,r..u-'t • W:1~ ··
would all11w a fn m!(O or!(.in to ht> ,K<eplt'1f ~..........-
prt·\~ lll !( 1111rnunity 111 all anti~cn ~ rtmain, .a , h~lltn!(t for
imnn1110lni,ti~t~ tnd..t y.
In (rrt ain inJividu.,I,. thr immunt cy,rem m,1lfun, 11,,n,
hy lmin r,( it~ ,rme of ,elf ,1mi nnmelf, wh1Lh p~rm11, ,m im-
mun e attalk on th e ho~!. 1 hi, wnd1r1,,n. autoimmunity,
c;i n oiu,c a numhcr of c.hron,c debilrr.ir1n~ d1wa\t'1. Tht
sy mpton,5 of autoimmunity differ, deprndrnit on whrch t1,-
sues and orgJm are und er alta(k. For txample. muh1plt
sclerosis is due to an autoim munt allack on • pmttin 1n
nerve shc,, th, in th e hrain and ctntral ntrvou~ .y\ttm,
Crohn's di!iea\e is an attack on intt,tinal ri,mt1. •nd
rh eumatoid arthr itis is an attack on joint\ of the h•nd,, ft~ .
flGURE 1- 14 Patient suffering swelling of the right eye from
arm s, and legs. The genetic and environment•! factor, th.1t
effects of allergic reaction to a bee sting. Such hypersensitivity
trigger and sustai n autoimmunt di~a~ art YCT'f oll(;five
reactions result from sensitization caused by previous exposure to the
areas of immunologic research, as is tht ~arch for im-
bee venom. Bee stings may cause pain, redness, and swelling as shown
proved treatments.
here or may cause systemic anaphylactic reactions that result in
If any components of in nate or ,pecific immun1tv ue
death if not quickly treated. {Dr. P. Marazzi/Photo Researchers.}
defective because of geneti c abnormal ity or if •ny 1mmunt
function is lost because of damage by chemKal, phv-.,ul,
or biological agents, the host suffers from unmunockfi-
or to the hospital emergency room (see Clinical Focus on ciency. The severity of the imm unodeficiency d1~~ de-
page 20). pends on the number of affected components. A common
When the immune system encounters foreign cells or tis- type of immunodeficiency in North America is a ~kctive
sue, it responds strongly to rid the host of the invader. The immunodeficiency in which only one type of im-
sam e response may be raised against mutant host cells, in- munoglobulin,Jg.A, is lacking; the symptoms m.1y be an in-
cluding cancer cells. However, in some cases, the transplan- crease in certain types of infections or the ckti.:~Tk.-Y mn
tation of cells or an organ from another individual, although even go unnoticed. In contrast, a rarer immunodc!fi.:~n~
viewed by the immune system as a foreign invasion, may be called severe combined immunodeficiency (SCID), ,11,.hi.:h
the only possible treatment for life-threatening disease. For affects both B and T cells, may result in de.lth from infec-
example, it is estimated that more than 70,000 persons in the tion at an early age if untreated. Since the 198(),s. tM most
L'nited States alone would benefit from a kidney transplant. common form of immunodeficiency has b«n .Kquired
The fact that the immune system will attack and reject any immune deficiency syndrome, or AIDS, whi.:h results from
transplanted organ that it recognizes as nonself raises a infection with the retrovirus human immunooc!ti.:ien..-v
formidable barrier to this potentially lifesaving treatment. virus, or HIV. In AIDS, T helper cells are destroyed b,, HI\',
An additional danger in transplantation is that any trans- causing a collapse of the immune system. It is t stimated
planted cells with immune function (for example, when that 40 million people worldwide sutl~r from this d.iS('".i~.
bone marrow is transplanted to restore immune function) which if not treated is usually fatal within 8 to 10 vears
may view the new host as nonself and react against it. This after infection. Although certain treatments .:an now ·pro-
reaction, which is termed graft-versus-host disease, can be long the life of AIDS patients, there is no known .:ure for
fatal. The rejection reaction and graft-versus-host disease the disease.
can be suppressed by drugs, but treatment with these drugs This chapter has been a brief introJudi\)n to the immune
suppresses general immune function, so that the host is no system, and it has given a thumbnail skeh:h of how this ..-om-
longer protected by its own immune system and becomes plex system functions to proted the host from J ise.1se. The
susceptible to infectious diseases. Transplantation studies following chapters will examine the stru.:tu re anJ fon..:ti\)ll
have played a major role in the development of immunol- of the individual cdls, organs, c1nJ mole..-ules that make up
ogy. A Nobel prize was awarded to Karl Landsteiner (men- this system. They will dt·s..-ribe our ..-urrent unJerst;mJing ,)f '-
tioned above for his contributions to the concept of immune how the components of immunit y intera..-t and the exp'-'ri-
specificity) in 1930 for the discovery of the human ABO ments that allowed disrnvery of these mnh,misms. Sp<..-ilk
blood groups, a finding that allowed blood transfusions to areas of applied immunology, su..-h clS immunity to intec-
be carried out safely. In 1980, G. Snell, J. Daussd, and B. tious disei\ses, cancer, current v,Kcination practi.:es, ,mJ the
Benacerraf were recognized for discovery of the major histo- major types of immune dysfundion are the subject of later
compatibility complex, and in 1991 , E. D. Thomas and chapters.
 20
PART
.....,_ ,' I• ~
I
I
INTRooucr,oN

hose treated in the

.. In addition to t'"" ()(JO hospitaliza-
all v1s1ts. bout 1ov, .h
Clf N1cAl F Ocus here were a . past year, wit an
ER, t thma ,n the
tions for as o 4 days.
Allergies and Asthma Are Serious Public avera g
e stay of 3 t
II ages a
nd races are af-
.
,. ________ Health Problems A lthough a
f om ast
hma are 3.5 times
.
ted deaths r African American .
I --------- --- fec • among
Although the i~~----··-··· -·······--·--- ----·-·· -·-···········- ·-- re common f r the increases 1n
rno sons o
to protect the host fro une system serves Flnit contm:t children. The rea a cases and for the higher
cer ina . m infection and can- ~•Ith an allc'"Mcn (raMWccd) number of asth~ American children re-
, Pj)ropnate responses of th. . African gh recent stu d'1es of
can lead to d. 1s system Hal!wrcd death rate 1n
. isease. Common among the re- althOU
SU(t5 of rmmune dysfu . polkn main unknown,_ llergic disease may hav,
and asth . nct1on are allergies genetic factors ,n a (see Clinical Focus in
ma, bo th senous public health prob- uncovered some clues
1
,~- Details of the mechanisms that under
chapter 15). ·ous health problem
,e .allergic and asthmatic responses t~
An increasingly se~1 Uy to peanuts and
envi~ntal antigens (or allergens) will be B cell
considered in Chapter 15 s· Iy stated, is food allergy, espec1ah s and walnuts).t
alle i . · imp (almonds, cas e'W •
. rg ~ reactions are responses to antigenic
stimuli that result in immunity based mainly
l lgE
I
Production of
tree nu~ 3 million Americans are al-
Approx1matelyf d and they are the lead-

~i~
i on the lgE dass of immunoglobulin. Expo- large amounts lergic to thesef or° t:; and near-fatal food
' sure to the antigen (or allergen) triggers an of ragweed IgE ing causes o a Ih h
. ( h lactic) reactions. A t ougf
lgE-mediated release of molecules that antibody allergic anap y
.. h &oods can prevent harm ul
cause symptoms ranging from sneezing and avo1d1ng t ese 1'
Pla,m, cell ) uences, the ubiquitous use. of peanut
dermatitis to inflammation of the lungs in ro~ eq .
. d other nut products m.. a vanety
an asthmatic attack. The sequence of events protein an
of foods makes avoidance very d1ff icult for
in an allergic response is depicted in the
accompanying figure.
IgE molecules the allergic individual. At least 50% of seri-
attach to mast ous reactions are caused by accidental ex-
The discomfort from common allergies cells
such as plant pollen allergy (often called posures to peanuts, tree nuts, or their
ragweed allergy) is short-lived, consisting of products. This has led to controversial
sneezing and runny nose--trivial in com- movements to ban peanuts from schools
Mast cell and airplanes.
parison to the effects of cancer, cardiac
arrest, or life-threatening infections. A more Anaphylaxis generally occurs within an
serious allergic reaction is asthma, a chronic Subsequent contact hour of ingesting the food allergen, and
disease of the lungs in which inflammation, with allergen the most effective treatment is injection
mediated by environmental antigens or of the drug epinephrine. Those prone to
infections, causes severe difficulty in breath- anaphylactic attacks often carry injectable
ing. According to 2002 statistics from the epinephrine to be used in case of exposure.
IgE-primed mast
Centers for Disease Control. 20 million peo- cell releases In addition to the suffering and anxiety
ple suffer from asthma in the United States, molecules that caused by inappropriate immune responses
and 12 million per year experience an cause wheezing, or al~ergies to environmental antigens,
sneezing, runny nose, there is a staggering cost-estimat ed to be
asthma attack. About 5000 people die each
watery eyes, and
year from asthma. In the past 20 years, the a_lmost $20 billioll-in terms of lost wor1c

I
other symptoms .
' prevalence of asthma in the Western world time for those affected and ,,or caregivers.
Th
ts
ese coS well ju5tify the extensive ef-
has doubled.•
f The importance of allergy as a public Sequence of events leading to an allergic forts by basic and clinical immunol ists
health problem is underscored by the fact and allergists to relieve the suffering caog d
response. When the antibody produced on by these disorders. use
that the annual numbers of doctor visit~ for
contact with an allergen is lgE, this class of
hypertension, routine medical examina-
antibody reacts with a mast cell Subse-
tions, or normal pregnancy are ea~h f~r quent reaction of the antibody-binding site
than the number of visits for allergic cond1- with the allergen triggers the mast cell to 'Holgate, s. T. , 999 The .
. I f ct the most common reason for asthma, Nature s . epidemic of allergy and
t1ons. n a , • which the lgE is bound to secrete molecules 'Hughes D A anUdpPC. to vol 402, 82.
. hos ital emergency room is an that cause the allergic symptoms. ' .., · Mills 2
' tnp to a p ting for one third of A problem on the rise Biol . - 001 . Food allergy.
~ - ~ - - - - - -- · 0g,Sf (London) 48:201.
asthma attack. accoun
-- -~-----.J
 7
ll

SUMMARY t ■ Use ful Web Sites

• lmm umtv i\· thC' •st.11 t, ' ,( I' "'t c-, 111,n 11~.i•mt forr,jln or!{,ln · htt p.//w ww HH i cr&f
.
•~~-1~ l,r .,u_h~tAlh'<"~ (ant,!,!rn~ I. \ 'rt ll'hr,1tr~ ha\'e lwo h.·pr1 I he• Amrri, .1n A, .i•l,m~ ,,( -\ 11.-ru ~•tl'lm
,t .tn<f
ot •mmumty: inn.Hr .ind adJJ 't""· lmm1111nlojfv ,ctr 1n<111,lr, ,In nt,n w.., l1hrn
v ,,(
···h' h i11ft1rrn.11111n 11hf,11t .tllf-r ," <f1'lt'.aw-,
• !nn,Ut> imm unity cnn, titut r\ a hr\t lme of Jrfr, iv• ... " ll
d ~ . lrnilr, th.it rl'l •
n, ~ t'~ r.ne~. rhagc"·yti1.. cl'lk anJ m11
I ·)
http .//ww w.u i 0,1
Ofn1 7(' certam d.1~..,-~ of ratho flrm .
· · 1hr Wrh ,,rr 11f th, Am,r1<,an ~•V1C1.111nn o(
and adap ttW' tmm umty OJ~ratr rnn11rrati\Th~ adi -
• lnn.1. tt" . ' '~11dls hnm unnl,~1,t, cont. 11n,, ,,,,"1 fit.ii, ,( mfor
m.ttir,n
vatn t th · · re~ro n~e pnidul..'cs 1o1
l n_o e mnatt" imm une of intrrr,t to 1mmunolo~1ct,
mune rr~p1111se.
that stimulate a suhM-quent adaptiq~ im
http ://ww w.ncbi.nlm.nrh pv/ ,u~ d/
ur immunologic at-
• A~artiv~ imm_un~ responses exhibit fo ti.t r~~
, mem ory, and sdf- nonsclf PubMrd, tht N.ition.il l.Jbr,u, 11( .\ ~dK •~
tnbu t~:. spectfioty, diversity m,11, nn puhl1 uhoM . " rhir ~i. r, ~
'"'°"'gmt1on. more thdn 9
sivr b1bl111 gr.iphK d.it.it>...w fot ~,c i~•I md
comprrhrn
immunity resides fr~ndlv 41ft
• :ine high degree of specifi city in adaptive biomedica l litr raturt. Jr is ,h,o a h,ghlr u~
and T-ceU recep tors) that recog -
1~ molecu!es (anti bodi es
nize md bmd specific antig ens.

• Antibodies recognize and interact direc

only antigen
tly with antigen.
combined with
~ Study Questions
T-cell recep tors recognize You han a ,oung ~ who ti.
com plex (MH C) molecules . CLINICAL Focus QUESTION
ma_ior histocompatibility b.it pttu urkm s
developed a severe allergy to tr~ nuts.. '-'t
lymphocytes are the Sbould ~
• The two majo r subpopulations of T would you advise for rum and for his parm ts,
oxic (T ) cells,
CD4.,. T helper ( TH) cells and CD8 + T cytot officials be aware of this cond ition ?
cells (CTL s). c
whic h give rise to cyto toxic T ious met.hods ~
I. Why was Jenner's vaccine supe rior to pR'V
m include common smallpox?
• Dysfunctions of the imm une syste conferring resistance to
mala dies such as allergies and asthm a as well as immuno- ur c.onra A'tlW °"
. 2. Did the treatment for rabies used bv Pastr
defici ency and autoimmunity passive immunity to the rabie s VU-U:S ?Is dlttt mv wn ID llrV
.
thW
at ~ tor iruatioD
References 3. Infants immediately after birth are often
o;cd 1or .J.
Theory of Acquired with group B streptococcus. A vaccine ~ prop
Burnet. F. M. 1959. The Clomil Selection ministration to women of child~arin ~ ~us . How QB am-
Press , Cambridge, MA.
Immunity. Cambridge University munizing the mothers help the babie s?
Cohen, S. G., and M. Samter. 1992. Exce
rpts from Classics in
CA. 4. Indicate to which branch(es ) of the imm
une )YStem the '°'·
Allergy. Symposia Foundation, Carlsbad, lowing statements apply, using H fur ~ humur.I br.m..:h
lated by A. F. and ediatt'd braJ'h:h. Some stc1te rMn~ lllclY
Desour, L J922. Pasteur and His Work (trans and CM for the cell-m ·
apply to both branches.
B. H. Wedd ). T. Fisher Unwin, London.
evolution and genetics a. Involves class I MHC molt"C ules
Kimbrell , D. A., and B. Beutler. 2001. The
Reviews Gene tics 2:256 . b. Responds to viral intection
of innate immunity. Nature
c. Involves T helper cells
Kindt, T. J., and J. D. Capra. J984. The Antib
ody Enigma. Plenum d. Involves processed anti~en
Press, New York. e. Responds following an organ transpl,m t
Serologic Reactions. f. Involves T cytotoxic cells
Landsteiner, K. I 94 7. The Specificity of g. Involves B cdls
Harvard University Pr~, , Cambridg e, MA.
h. Involves T cells
Transplantation : The tion
Medawar, P. B. 1958. The Immunology of i. Responds to extrai:dlular b.icteri.il inh
emic Press, New York. secrl'led antihody
Harvey Lectures, 1956-1957. Acad j. Involves
Jnfectiuus Diseases. k. Kills virus -inleded self cells
Metchnikoff, E. J905. Immunity in the cttristic attributes,
Macmillan, New York. 5. Adaptive immunity exhibits four chara
these four at-
ing system. Scientific which are mediated by lymphol.'ytes. List
O'Neill, A. J. 2005 . Immunity's early warn tributes and briefly explain how they arise .
American 292:38. une response that
6. Name three features of a secondary imm
Paul, W., ed. 2003. Fundamental Immunolog
y, 5th ed. Lippincott nse.
distinguish it from a primary immune respo
Williams & Wilkins, Philadelphia. of antigen-binding
7. Compare and contrast the four types
Encyclopedia of Im- tibodies, T-cell
Ruitt , I. M., and P. J. Delves, eds. 1998. An molecules used by the imm une syste m-an
, London.
munology, 2nd ed., vols. 1-4. Academic Press
22
l f'i 111()[llf( 1ION
n in , olution (with.
j; c ant1gc
rcc. 11 14 n
)(''i c,111 ,
I 1YI l
I1. l\oth lei
ti . ex trdtC•llular matrix-oound
11111 (I' , ). ,c~ rcc.ogn ite
' 11111h cl'll tYI tcd by d.i'>~ I or da.,, II
.
r1 11tif\c11, . . c ·1nt 1.gcn prc<ien
d. ·r (dhnll Iyr ,•~ogn 11 '
11
l 11 I<: 111ol<'l 1c~.
,. indicat e whether t~"
tatcmc nt'i,
followi ng h · h' k the .,,arem cnt I\. fa'(,I
\ h1 r cal h o ( t 1,c (·11,c. If you t ,n
I • . t uc or ,
, IJfr llll'lll ,,r
tun ·t • - - - - , .111d ___ __ oll rx,,l,1in why. b u,e repeated expo'iu r, to
ion"~ .11111~,' n pr,' ~ntin~ '-l'lk ·red eca
h• Antl •~,·n \tcr \hot'i arc rcqu1 immun e re'tpon..e.
· 1, r(',,,ntm1_1. '-di, J d l\·cr a ___ __ , ignal a. Hoo . ··n builch a ~tronge r must be cut and ,plictd
t<' - - - - - cdk · "" ant1gc
The gene for the
·r II recepto r L
c. O nlv· ant iol•n· rrot:nt111
- , • · g.n• 11 ,n.prr ,s d,,,\ b. cc . ctions, before it can uc Iran-
:- _ _ _ __ I
togr1hcr, dc ct1ng. entire sc
mnkn1k , "h . .
• 'rt:d\ nr.1rIy all cdls r xprc,~ dJs~
- - - - - Ml IC mohu lcs. ~crihed . h greatest o nslaught fro m fo reign in-
d. The- ,,:icnti h( ll·rm thJt rcfrrs to white blood cdls in Our bodies face t e membr anes.
E:rnt'r.ii is _ _ _ _ _ _ _ __ c. hour mucus . t
vaJcrs throug . f , ·body in the immun e sys em
e. The d duction o an J
arm o f t I1e immun
. d. Increase pro ce of antigen.
e system 1.s so is driven by th e pre~en
cc1II~ hc.-cau, e antiho Jies are generated in response to b T cells.
specific p.11hogens. Prior exposure to a pathogr n is e. Antigen is bound directI : tindin g deft of class MHC I
requm.·d for this part of the immune system to develop. f. Peptides are added to \ e
f. T cells must have corecertors so they can efficiently bind molecules in the cytoso · . to plasma cells they need
g. In order for B cells to mature m
to MHC molecules. The coreceptor for recognition of
cl.bS l MHC is _ _ _ and the coreceptor for recogni- "help" from T cells.
tion of class II is called - - - -· 14. Match the ce11 type WI'th the receptor found on that cell.
g. The part of the antigen bound by an antibody is known
asthe _ _ _ __ Cell Type Receptor
9. The T cell is said to be class I restricted. What does this mean? a. Antigen presenting cell 1. cos+
b. B cell 2. MHC
10. Innate and adaptive immunity act in cooperative and inter-
c. Helper T cell 3. BCR
depend ent ways to protect the host. Discuss the collabora-
tion of th~ two forms of immunity. d. Cytotoxic T cell 4. co4+
11. Give examples of mild and severe consequences of immune
dnfunc tion. What is the most common cause of immuno-
d~ficiency throug hout the world today?
" Interactive Study
t 2. Which of the following statements about how B and T cells
recognize antigen are true? www.whfre eman. com/k uby
a. Hcell~only recognize antigen presented by class I or class II
~1HC molecules. 0 SELF-TEST
Review of Key Terms