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PATHO - CH08 the Immune Response (Porth)
ISBN: 0781746450 Designed to provide students with essential concepts of dis...
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chapter
1
I
Historical Perspective
I
Innate Immunity
I
Adaptive Immunity
I
Comparative Immunity
I
Immune Dysfunction and Its Consequences
Numerous T Lymphocytes Interacting with a SingleMacrophage
Overview oftheImmune System
T
defense system that has evolved to protect animalsfrom invading pathogenic microorganisms andcancer.It is able to generate an enormous variety ofcells andmolecules capable ofspecifically recognizing and eliminat-ing an apparently limitless variety offoreign invaders.Thesecells and molecules act together in a dynamic network whosecomplexity rivals that ofthe nervous system.Functionally,an immune response can be divided intotwo related activities—recognition and response.Immunerecognition is remarkable for its specificity.The immunesystem is able to recognize subtle chemical differences thatdistinguish one foreign pathogen from another.Further-more,the system is able to discriminate between foreignmolecules and the body’s own cells and proteins.Once a for-eign organism has been recognized,the immune systemrecruits a variety ofcells and molecules to mount an appro-priate response,called an
effector response,
to eliminate orneutralize the organism.In this way the system is able toconvert the initial recognition event into a variety ofeffectorresponses,each uniquely suited for eliminating a particulartype ofpathogen.Later exposure to the same foreign organ-ism induces a
memory response,
characterized by a morerapid and heightened immune reaction that serves to elimi-nate the pathogen and prevent disease.This chapter introduces the study ofimmunology froman historical perspective and presents a broad overview of the cells and molecules that compose the immune system,along with the mechanisms they use to protect the body against foreign invaders.Evidence for the presence ofvery simple immune systems in certain invertebrate organismsthen gives an evolutionary perspective on the mammalianimmune system,which is the major subject ofthis book.El-ements ofthe primitive immune system persist in verte-brates as
innate immunity
along with a more highly evolvedsystem ofspecific responses termed
adaptive immunity
.These two systems work in concert to provide a high degreeofprotection for vertebrate species.Finally,in some circum-stances,the immune system fails to act as protector becauseofsome deficiency in its components;at other times,it be-comes an aggressor and turns its awesome powers against itsown host.In this introductory chapter,our description of immunity is simplified to reveal the essential structures andfunction ofthe immune system.Substantive discussions,ex-perimental approaches,and in-depth definitions are left tothe chapters that follow.Like the later chapters covering basic topics in immu-nology,this one includes a section called “Clinical Focus”that describes human disease and its relation to immunity.These sections investigate the causes,consequences,or treat-ments ofdiseases rooted in impaired or hyperactive immunefunction.
Historical Perspective
The discipline ofimmunology grew out ofthe observationthat individuals who had recovered from certain infectiousdiseases were thereafter protected from the disease.TheLatin term
immunis,
meaning “exempt,”is the source oftheEnglish word immunity,meaning the state ofprotectionfrom infectious disease.Perhaps the earliest written reference to the phenomenonofimmunity can be traced back to Thucydides,the great his-torian ofthe Peloponnesian War.In describing a plague inAthens,he wrote in 430
BC
that only those who had recov-ered from the plague could nurse the sick because they would not contract the disease a second time.Although early societies recognized the phenomenon ofimmunity,almost
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two thousand years passed before the concept was success-fully converted into medically effective practice.The first recorded attempts to induce immunity deliber-ately were performed by the Chinese and Turks in the fif-teenth century.Various reports suggest that the dried crustsderived from smallpox pustules were either inhaled into thenostrils or inserted into small cuts in the skin (a techniquecalled
variolation
).In 1718,Lady Mary Wortley Montagu,thewife ofthe British ambassador to Constantinople,observedthe positive effects ofvariolation on the native populationand had the technique performed on her own children.Themethod was significantly improved by the English physicianEdward Jenner,in 1798.Intrigued by the fact that milkmaidswho had contracted the mild disease cowpox were subse-quently immune to smallpox,which is a disfiguring and of-ten fatal disease,Jenner reasoned that introducing fluid froma cowpox pustule into people (i.e.,inoculating them) mightprotect them from smallpox.To test this idea,he inoculatedan eight-year-old boy with fluid from a cowpox pustule andlater intentionally infected the child with smallpox.As pre-dicted,the child did not develop smallpox.Jenner’s technique ofinoculating with cowpox to protectagainst smallpox spread quickly throughout Europe.How-ever,for many reasons,including a lack ofobvious diseasetargets and knowledge oftheir causes,it was nearly a hun-dred years before this technique was applied to other dis-eases.As so often happens in science,serendipity incombination with astute observation led to the next majoradvance in immunology,the induction ofimmunity tocholera.Louis Pasteur had succeeded in growing the bac-terium thought to cause fowl cholera in culture and then hadshown that chickens injected with the cultured bacterium de-veloped cholera.After returning from a summer vacation,heinjected some chickens with an old culture.The chickens be-came ill,but,to Pasteur’s surprise,they recovered.Pasteurthen grew a fresh culture ofthe bacterium with the intentionofinjecting it into some fresh chickens.But,as the story goes,his supply ofchickens was limited,and therefore he used thepreviously injected chickens.Again to his surprise,the chick-ens were completely protected from the disease.Pasteurhypothesized and proved that aging had weakened the viru-lence ofthe pathogen and that such an attenuated strainmight be administered to protect against the disease.Hecalled this attenuated strain a
vaccine
(from the Latin
vacca
,meaning “cow”),in honor ofJenner’s work with cowpoxinoculation.Pasteur extended these findings to other diseases,demon-strating that it was possible to
attenuate,
or weaken,apathogen and administer the attenuated strain as a vaccine.In a now classic experiment at Pouilly-le-Fort in 1881,Pas-teur first vaccinated one group ofsheep with heat-attenuatedanthrax bacillus (
Bacillus anthracis
);he then challenged thevaccinated sheep and some unvaccinated sheep with a viru-lent culture ofthe bacillus.All the vaccinated sheep lived,andall the unvaccinated animals died.These experimentsmarked the beginnings ofthe discipline ofimmunology.In1885,Pasteur administered his first vaccine to a human,a young boy who had been bitten repeatedly by a rabid dog(Figure 1-1).The boy,Joseph Meister,was inoculated with aseries ofattenuated rabies virus preparations.He lived andlater became a custodian at the Pasteur Institute.
Early Studies Revealed Humoral and CellularComponents of the Immune System
Although Pasteur proved that vaccination worked,he did notunderstand how.The experimental work ofEmil vonBehring and Shibasaburo Kitasato in 1890 gave the first in-sights into the mechanism ofimmunity,earning von Behringthe Nobel prize in medicine in 1901 (Table 1-1).Von Behringand Kitasato demonstrated that
serum
(the liquid,noncellu-lar component ofcoagulated blood) from animals previously immunized to diphtheria could transfer the immune state tounimmunized animals.In search ofthe protective agent,var-ious researchers during the next decade demonstrated thatan active component from immune serum could neutralizetoxins,precipitate toxins,and agglutinate (clump) bacteria.In each case,the active agent was named for the activity it ex-hibited:antitoxin,precipitin,and agglutinin,respectively.
2
PART I
Introduction
FIGURE
1
-
1
Wood engraving of Louis Pasteur watching JosephMeister receive the rabies vaccine. [
From
Harper’s Weekly
29
:
836
;courtesy of the National Library of Medicine.
]
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Initially,a different serum component was thought to be re-sponsible for each activity,but during the 1930s,mainly through the efforts ofElvin Kabat,a fraction ofserum firstcalled gamma-globulin (now
immunoglobulin
) was shownto be responsible for all these activities.The active moleculesin the immunoglobulin fraction are called
antibodies.
Be-cause immunity was mediated by antibodies contained inbody fluids (known at the time as humors),it was called hu-moral immunity.In 1883,even before the discovery that a serum compo-nent could transfer immunity,Elie Metchnikoffdemon-strated that cells also contribute to the immune state ofananimal.He observed that certain white blood cells,which hetermed
phagocytes,
were able to ingest (phagocytose) mi-croorganisms and other foreign material.Noting that thesephagocytic cells were more active in animals that had beenimmunized,Metchnikoffhypothesized that cells,rather thanserum components,were the major effector ofimmunity.The active phagocytic cells identified by Metchnikoffwerelikely blood monocytes and neutrophils (see Chapter 2).In due course,a controversy developed between thosewho held to the concept ofhumoral immunity and thosewho agreed with Metchnikoff’s concept of
cell-mediated im-munity.
It was later shown that both are correct—immunity requires both cellular and humoral responses.It was difficultto study the activities ofimmune cells before the develop-ment ofmodern tissue culture techniques,whereas studieswith serum took advantage ofthe ready availability ofbloodand established biochemical techniques.Because ofthesetechnical problems,information about cellular immunity lagged behind findings that concerned humoral immunity.In a key experiment in the 1940s,Merrill Chase succeededin transferring immunity against the tuberculosis organismby transferring white blood cells between guinea pigs.Thisdemonstration helped to rekindle interest in cellular immu-nity.With the emergence ofimproved cell culture techniquesin the 1950s,the
lymphocyte
was identified as the cell re-sponsible for both cellular and humoral immunity.Soonthereafter,experiments with chickens pioneered by BruceGlick at Mississippi State University indicated that there were
Overview of the Immune System
CHAPTER
1
3
TABLE
1
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1
Nobel Prizes for immunologic research
Year Recipient Country Research
1901
Emil von BehringGermanySerum antitoxins
1905
Robert KochGermanyCellular immunity to tuberculosis
1908
Elie Metchnikoff RussiaRole of phagocytosis (Metchnikoff) andPaul EhrlichGermanyantitoxins (Ehrlich) in immunity
1913
Charles RichetFranceAnaphylaxis
1919
Jules BorderBelgiumComplement-mediated bacteriolysis
1930
Karl LandsteinerUnited StatesDiscovery of human blood groups
1951
Max TheilerSouth AfricaDevelopment of yellow fever vaccine
1957
Daniel BovetSwitzerlandAntihistamines
1960
F. Macfarlane BurnetAustraliaDiscovery of acquired immunologicalPeter MedawarGreat Britaintolerance
1972
Rodney R. PorterGreat BritainChemical structure of antibodiesGerald M. EdelmanUnited States
1977
Rosalyn R. YalowUnited StatesDevelopment of radioimmunoassay
1980
George SnellUnited StatesMajor histocompatibility complexJean DaussctFranceBaruj BenacerrafUnited States
1984
Cesar MilsteinGreat BritainMonoclonal antibodyGeorges E. KöhlerGermanyNiels K. JerneDenmarkImmune regulatory theories
1987
Susumu TonegawaJapanGene rearrangement in antibodyproduction
1991
E. Donnall ThomasUnited StatesTransplantation immunologyJoseph MurrayUnited States
1996
Peter C. DohertyAustraliaRole of major histocompatibility complexRolf M. ZinkernagelSwitzerlandin antigen recognition by by T cells
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