Immunology, Fifth Edition

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Immune Macrophagerecognition is remarkable for its specificity.

The immunesystem is able to recognize subtle chemical differences thatdistinguish one foreign pathogen from another. Once a for-eign organism has been recognized, the immune system I Adaptive Immunityrecruits a variety of cells and molecules to mount an appro- I Comparative Immunitypriate response, called an effector response, to eliminate orneutralize the organism. In this way the system is able to I Immune Dysfunction and Its Consequencesconvert the initial recognition event into a variety of effectorresponses, each uniquely suited for eliminating a particulartype of pathogen.

Later exposure to the same foreign organ-ism induces a memory response, characterized by a morerapid and heightened immune reaction that serves to elimi- Like the later chapters covering basic topics in immu-nate the pathogen and prevent disease. Evidence for the presence of verysimple immune systems in certain invertebrate organismsthen gives an evolutionary perspective on the mammalianimmune system, which is the major subject of this book.

El- Historical Perspectiveements of the primitive immune system persist in verte- The discipline of immunology grew out of the observationbrates as innate immunity along with a more highly evolved that individuals who had recovered from certain infectioussystem of specific responses termed adaptive immunity. Finally, in some circum- English word immunity, meaning the state of protectionstances, the immune system fails to act as protector because from infectious disease.

In this introductory chapter, our description of torian of the Peloponnesian War. In describing a plague inimmunity is simplified to reveal the essential structures and Athens, he wrote in BC that only those who had recov-function of the immune system. Substantive discussions, ex- ered from the plague could nurse the sick because theyperimental approaches, and in-depth definitions are left to would not contract the disease a second time.

Although earlythe chapters that follow. 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 , Lady Mary Wortley Montagu, thewife of the British ambassador to Constantinople, observedthe positive effects of variolation on the native populationand had the technique performed on her own children.

Themethod was significantly improved by the English physicianEdward Jenner, in 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. 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.

How-ever, for many reasons, including a lack of obvious diseasetargets and knowledge of their 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 of immunity to FIGURE Wood engraving of Louis Pasteur watching Josephcholera. Louis Pasteur had succeeded in growing the bac- Meister receive the rabies vaccine.

After returning from a summer vacation, heinjected some chickens with an old culture. Pasteur young boy who had been bitten repeatedly by a rabid dogthen grew a fresh culture of the bacterium with the intention Figure The boy, Joseph Meister, was inoculated with aof injecting it into some fresh chickens. But, as the story goes, series of attenuated rabies virus preparations. He lived andhis supply of chickens was limited, and therefore he used the later became a custodian at the Pasteur Institute.

Again to his surprise, the chick-ens were completely protected from the disease. Pasteur Early Studies Revealed Humoral and Cellularhypothesized and proved that aging had weakened the viru-lence of the pathogen and that such an attenuated strain Components of the Immune Systemmight be administered to protect against the disease. He Although Pasteur proved that vaccination worked, he did notcalled this attenuated strain a vaccine from the Latin vacca, understand how.

Von Behringstrating that it was possible to attenuate, or weaken, a and Kitasato demonstrated that serum the liquid, noncellu-pathogen and administer the attenuated strain as a vaccine. In search of the protective agent, var-anthrax bacillus Bacillus anthracis ; he then challenged the ious researchers during the next decade demonstrated thatvaccinated sheep and some unvaccinated sheep with a viru- an active component from immune serum could neutralizelent culture of the bacillus.

All the vaccinated sheep lived, and toxins, precipitate toxins, and agglutinate clump bacteria. These experiments In each case, the active agent was named for the activity it ex-marked the beginnings of the discipline of immunology. In hibited: antitoxin, precipitin, and agglutinin, respectively.


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Immunology, Fifth Edition

It was later shown that both are correct—immunityto be responsible for all these activities. The active molecules requires both cellular and humoral responses. It was difficultin the immunoglobulin fraction are called antibodies.

Gehas Rosens Case Studies in Immunology 5th Fifth edition Paperback2007

Be- to study the activities of immune cells before the develop-cause immunity was mediated by antibodies contained in ment of modern tissue culture techniques, whereas studiesbody fluids known at the time as humors , it was called hu- with serum took advantage of the ready availability of bloodmoral immunity. Because of these In , even before the discovery that a serum compo- technical problems, information about cellular immunitynent could transfer immunity, Elie Metchnikoff demon- lagged behind findings that concerned humoral immunity.

He observed that certain white blood cells, which he in transferring immunity against the tuberculosis organismtermed phagocytes, were able to ingest phagocytose mi- by transferring white blood cells between guinea pigs. Thiscroorganisms and other foreign material. Noting that these demonstration helped to rekindle interest in cellular immu-phagocytic cells were more active in animals that had been nity. With the emergence of improved cell culture techniquesimmunized, Metchnikoff hypothesized that cells, rather than in the s, the lymphocyte was identified as the cell re-serum components, were the major effector of immunity.

SoonThe active phagocytic cells identified by Metchnikoff were thereafter, experiments with chickens pioneered by Brucelikely blood monocytes and neutrophils see Chapter 2. Glick at Mississippi State University indicated that there were 4.

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The controversy tibody molecule. According to the instructional theories, aabout the roles of humoral and cellular immunity was re- particular antigen would serve as a template around whichsolved when the two systems were shown to be intertwined, antibody would fold. The antibody molecule would therebyand that both systems were necessary for the immune assume a configuration complementary to that of the antigenresponse.


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This concept was first postulated by Friedrich Breinl and Felix Haurowitz about and redefined in theEarly Theories Attempted to Explain s in terms of protein folding by Linus Pauling. The in-the Specificity of the Antibody— structional theories were formally disproved in the s, by which time information was emerging about the structure ofAntigen Interaction DNA, RNA, and protein that would offer new insights intoOne of the greatest enigmas facing early immunologists was the vexing problem of how an individual could make anti-the specificity of the antibody molecule for foreign material, bodies against almost anything.

Around , Jules Bordet at the Pasteur new experimental data and, through the insights of NielsInstitute expanded the concept of immunity by demonstrat- Jerne, David Talmadge, and F. Macfarlane Burnet, were re-ing specific immune reactivity to nonpathogenic substances, fined into a theory that came to be known as the clonal-such as red blood cells from other species.

Serum from an an- selection theory.

According to this theory, an individualimal inoculated previously with material that did not cause lymphocyte expresses membrane receptors that are specificinfection would react with this material in a specific manner, for a distinct antigen. This unique receptor specificity is de-and this reactivity could be passed to other animals by trans- termined before the lymphocyte is exposed to the antigen.

The work of Karl Landsteiner Binding of antigen to its specific receptor activates the cell,and those who followed him showed that injecting an animal causing it to proliferate into a clone of cells that have thewith almost any organic chemical could induce production same immunologic specificity as the parent cell. The clonal-of antibodies that would bind specifically to the chemical. In addition, it was shown that molecules differing in Adaptive Componentsthe smallest detail could be distinguished by their reactivity Immunity—the state of protection from infectious diseasewith different antibodies.

Two major theories were proposed —has both a less specific and more specific component. Theto account for this specificity: the selective theory and the in- less specific component, innate immunity, provides the firststructional theory. Most components of innate The earliest conception of the selective theory dates to Paul immunity are present before the onset of infection and con-Ehrlich in PhagocyticBorrowing a concept used by Emil Fischer in to explain cells, such as macrophages and neutrophils, barriers such asthe interaction between an enzyme and its substrate, Ehrlich skin, and a variety of antimicrobial compounds synthesizedproposed that binding of the receptor to an infectious agent by the host all play important roles in innate immunity.

Inwas like the fit between a lock and key. Ehrlich suggested that contrast to the broad reactivity of the innate immune sys-interaction between an infectious agent and a cell-bound tem, which is uniform in all members of a species, the spe-receptor would induce the cell to produce and release more cific component, adaptive immunity, does not come intoreceptors with the same specificity.

Exposure to the same antigen somecell-bound receptor; it is the soluble form that is secreted time in the future results in a memory response: the immunerather than the bound form released. Overview of the Immune System CHAPTER 1 5the first, is stronger, and is often more effective in neutraliz- distinct layers: a thinner outer layer—the epidermis—and aing and clearing the pathogen. The major agents of adaptive thicker layer—the dermis. The epidermis contains severalimmunity are lymphocytes and the antibodies and other layers of tightly packed epithelial cells.

The outer epidermalmolecules they produce. The sebaceous glands are as-pathogen. In general, most of the microorganisms encoun- sociated with the hair follicles and produce an oily secretiontered by a healthy individual are readily cleared within a few called sebum. Sebum consists of lactic acid and fatty acids,days by defense mechanisms of the innate immune system which maintain the pH of the skin between 3 and 5; this pHbefore they activate the adaptive immune system.

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A few bacteria that metabolize sebum live as commensals on the skin and sometimes cause a severe form of acne. One acne drug, isotretinoin Accutane , is a vitamin A derivative that pre-Innate Immunity vents the formation of sebum. Innate immunity can be seen to comprise four types of de- Breaks in the skin resulting from scratches, wounds, orfensive barriers: anatomic, physiologic, phagocytic, and in- abrasion are obvious routes of infection. The skin may alsoflammatory Table The protozoan that causes malaria, for example, is depositedProtective Barriers Against Infection in humans by mosquitoes when they take a blood meal.

The skin and the surface of mucous membranes are The conjunctivae and the alimentary, respiratory, andincluded in this category because they are effective barriers to urogenital tracts are lined by mucous membranes, not by thethe entry of most microorganisms.

Manual of Allergy and Immunology Fifth Edition — Hanz Medshoppe

The skin consists of two dry, protective skin that covers the exterior of the body. Acidic environment pH 3—5 retards growth of microbes. Mucous membranes Normal flora compete with microbes for attachment sites and nutrients. Mucus entraps foreign microorganisms. Cilia propel microorganisms out of body. Physiologic barriers Temperature Normal body temperature inhibits growth of some pathogens. Fever response inhibits growth of some pathogens. Low pH Acidity of stomach contents kills most ingested microorganisms.

Chemical mediators Lysozyme cleaves bacterial cell wall. Interferon induces antiviral state in uninfected cells. Complement lyses microorganisms or facilitates phagocytosis. Toll-like receptors recognize microbial molecules, signal cell to secrete immunostimulatory cytokines. Collectins disrupt cell wall of pathogen. Specialized cells blood monocytes, neutrophils, tissue macrophages internalize phagocytose , kill, and digest whole microorganisms. Inflammatory barriers Tissue damage and infection induce leakage of vascular fluid, containing serum proteins with antibacterial activity, and influx of phagocytic cells into the affected area.