Immunology

Introduction to Part I

Immunity
Immunity
The immune system is a collection of organs and vessels in the body in-
volved in producing and delivering the cells and molecules that protect
The Inflammatory Response
us from infections. Immunology is the study of the immune system and its
Immunopathology (the Double-Edged
Sword)
products and mechanisms of defense. From the time of conception, the
human organism faces attack from a wide variety of infectious agents.
Summary
We must have ways to identify them and defend ourselves against their
Bibliography
invasion, colonization, and toxic effects. This defensive ability is called
immunity.
“Immunity” comes from the Latin word immunitas, which means
“protection from.” In legal terms, immunity means that the protected
person is not subject to certain laws (e.g., diplomatic immunity) or is ex-
empt from certain duties (e.g., not required to serve in the armed
forces). In clinical terms, immunity means protection from certain dis-
eases, particularly infectious diseases. For instance, the commonly used
statement “She is immune to measles” indicates that the person referred
to has had measles once (or has been vaccinated against measles) and
will not get measles again. This is a form of acquired immunity or adap-
tive immunity.
The protective mechanisms of the body are divided into two major
types: innate and adaptive (Table 1.1). Innate resistance is present in all
normal individuals, does not require previous exposure to be effective,
and operates on infectious agents in the same way every time the individ-
ual is exposed. The adaptive, specific immune defense system does not be-
come active until the individual is exposed to the infectious agent; it re-
quires stimulation or immunization to become activated. This system has
the capacity to identify foreign agents and distinguish foreign agents from
self (self and nonself discrimination). It is mediated by products that
specifically recognize one agent and do not act on a different agent. In an
infectious disease, such as measles, the adaptive immune system is acti-
vated during the first infection, so that upon subsequent contact with
measles, no disease will occur. The immune system has learned to recog-
nize the measles virus and react specifically to it with an accelerated pro-
tective response. This is termed immune memory.

3
4 CHAPTER 1

Table 1.1 Comparison of innate and adaptive (acquired) immunity

Characteristic Innate immunity Adaptive immunity

Specificity Nonspecific, indiscriminate Specific, discriminate
Mechanical Skin, mucous membrane Immune induced reactive fibrosis
(granuloma)
Humoral pH, lysozyme, serum proteins Immunoglobulin antibodies
Cellular White blood cells Specifically sensitized lymphocytes
Induction Constitutive Requires previous contact (immunization)

Innate Immunity
Innate defense mechanisms against foreign invaders include mechanical
barriers, secreted products, and inflammatory cells (Fig. 1.1). Innate resis-
tance is present at all times in normal individuals. Its effectiveness may be
modulated by physiological conditions (e.g., nutrition, age, hormone lev-
els). Innate resistance does not distinguish among microorganisms of dif-
ferent species and does not alter in intensity upon reexposure. One of the
major nonspecific defense systems is the epithelial surface of the body. Ex-
ternally, the skin, and internally, the mucous membrane linings of the gas-
trointestinal tract and the epithelium of the airways of the lungs, provide
mechanical barriers to invasion. Secreted products, such as acid in the
stomach, lysozyme in tears, sebaceous gland secretions, and certain pro-
teins in the blood, are toxic to potential invaders. In addition, Paneth cells
at the bottom of intestinal crypts and epithelial cells, as well as phagocytic
cells, produce small antimicrobial peptides called defensins that can insert
into microbial membranes and disrupt them. White blood cells are at-
tracted to sites of infection by products of infecting organisms, necrotic tis-
sue, and defensins and attack the invaders.
When the protective epithelial barriers are breached (as by a cut or
abrasion of the skin or by penetration of invading organisms past the pro-
tective lining of the airways of the lungs), and organisms begin to grow in
the tissues of the body, a more specific and more powerful backup defense
system is needed. Since most infectious organisms can multiply rapidly,
and the defensive reaction must be directed specifically to the infection
and not to host tissues, this system must be activated quickly, be precisely
directed to the infectious agent, and be very destructive.

Adaptive Immunity
The adaptive immune system is quiescent until it is stimulated by a spe-
cific infection or vaccination (immunizing event). Agents that stimulate the
adaptive system of immunity are recognized as foreign by the immune
system and are called immunogens or antigens. The adaptive system is ca-
pable of exquisitely distinguishing among different microorganisms and
significantly alters its intensity and response time upon reexposure.
There are two major arms of the immune response: humoral and cellu-
lar. Humoral immunity is mediated by soluble protein molecules known
as antibodies. Cellular immunity is mediated by specifically sensitized
white blood cells known as lymphocytes. Immunization or vaccination may
activate two different classes of lymphocytes. The cells responsible for an-
tibody production are in the B-lymphocyte series; those responsible for cel-
lular immunity are in the T-lymphocyte series (Table 1.2). Antibodies belong
to a family of molecules termed immunoglobulins that are found in the
 Introduction to Part I 5

Sebaceous
Waxy
secretions
secretions

Tears
(lysozyme)

Nonpenetration
(stratified squamous epithelium)

Mucus

Mucus
Mucus
Saliva

Lysozyme
Lysozyme

Enzymes Acid

Gut
flora
Antibodies

Mucus
Sweat

GI tract
UG
tract

Egestion
Urine
washed
away

Figure 1.1 Innate immunity. Innate defenses against infectious agents include
skin and mucous membrane barriers and secretions that are bacteriostatic or re-
move foreign agents by washing them away. GI, gastrointestinal; UG, urogenital.
6 CHAPTER 1

Table 1.2 Two major arms of immunity

Characteristic Humoral immunity Cellular immunity

Cell line B cells, plasma cells T cells
Product Antibody Sensitized cells
Protection against: Bacteria, viruses Viruses, mycobacteria, fungi

blood or in external secretions. Antibodies are protein molecules that react

specifically with structures (epitopes) on infecting organisms through spe-
cialized receptors (binding sites or paratopes) on the antibody molecule.
Specifically sensitized T cells also have an antibodylike receptor (T-cell re-
ceptor), which recognizes antigens. Antigens that are capable of inducing
an immune response are called immunogens or complete antigens. Incomplete
antigens or haptens can elicit a reaction in an already immunized individual
but cannot induce an immune reaction in an individual who is not immu-
nized. The cells activated by immunization proliferate and differentiate in
specialized organs in the body (lymphoid organs) and are released into the
blood through specialized vessels known as lymphatics. This system al-
lows rapid delivery to other parts of the body, where an infection may be
located.
The response of the immune system to immunization has been com-
pared to a motor neuron reflex arc, i.e., there are afferent, efferent, and cen-
tral limbs. Afferent refers to delivery of the immunogen to cells of the im-
mune system; central refers to the response of the reacting lymphoid
organs resulting in production of antibody and sensitized cells; efferent
refers to the delivery of these products to the site of antigen deposition.
Once immunization has occurred, the immunized individual will respond
with a more rapid and more intense response upon second exposure to the
same immunogen (secondary response or immunological memory).
When an infectious agent begins to grow in our bodies, a “race of life”
is started. The race is between the rate of expansion of the infection and
the ability of our immune systems to combat the infection. When the anti-
body or sensitized cells react with antigen (infectious agent) in the tissues,
very powerful immune defense mechanisms are activated. However, the
infectious invaders of our bodies have many ways of evading both innate
and adaptive resistance. These include such properties as the release of
“toxins,” the formation of protective coatings, the ability to localize in in-
accessible sites, and the ability to exist within our own cells or even be in-
corporated into our DNA and thus evade recognition or destruction. Thus,
the immune system must not only react quickly, specifically, and power-
fully to an infection but must also react in a way that will overcome the
evasive mechanisms of the infectious agent. Different ways in which the
immune system combines specificity with the properties of inflammation
are called immune effector mechanisms. Some of the critical characteristics of
the adaptive immune system are listed in Table 1.3.

The Inflammatory Response

The response of our bodies to an infection occurs in the form of inflamma-
tion. The characteristics of inflammation may be modified by the presence
of antibody or sensitized cells. The hallmark of an inflammatory response
is the passage of proteins, fluid, and cells from the blood into focal areas in
 Introduction to Part I 7

Table 1.3 Functional abilities of the adaptive immune system

1. Specific recognition of many different foreign invaders

2. Rapid synthesis of immune products upon contact with invaders
3. Quick delivery of the immune products to the site of infection
4. Diversity of effector defensive mechanisms to combat infectious agents with different
properties
5. Nonself direction of the defensive mechanisms specifically to foreign invaders rather than
one’s own tissue
6. Deactivation mechanisms to turn off the system when the invader has been cleared

tissues. The result is the local delivery of agents that can effectively com-
bat infections. During an inflammatory response, components of both the
innate and adaptive resistance mechanisms are often used. These include
inflammatory cells, products of inflammatory cells, and certain blood pro-
teins (inflammatory mediators).
Initiation of an inflammatory response begins with an increase in
blood flow to infected tissues and with the opening of the cells lining the
blood vessels or capillaries, followed by emigration of cells into the in-
volved tissue (Fig. 1.2). Increased blood flow and vascular permeability
allow fluid and/or cells to enter the tissues. The gross manifestations of

Figure 1.2 Acute inflammatory response to infection. Infectious organisms re-

lease chemicals or initiate tissue damage that produces products that are chemo-
tactic for (attract) inflammatory cells (polymorphonuclear leukocytes) and cause
constriction of vascular endothelial cells. This results in passage of fluid from the
blood into the tissue (edema) and/or infiltration of tissue with inflammatory cells.
Polymorphonuclear leukocytes may ingest and kill the infecting organisms or may
release proteolytic enzymes into tissue, causing necrosis and formation of pus. An-
tibody serves to enhance this response and direct the inflammatory cells by react-
ing with the infecting organisms and activating bloodborne inflammatory media-
tors brought into the tissue during edema formation. These mediators react with
cell surface receptors on the inflammatory cells and enhance the ability of the cells
to ingest (phagocytose) and destroy the organisms.

Polymorphonuclear
leukocytes
INFECTIOUS
ORGANISMS

Chemoattractants

Microbial
killing

Pus
8 CHAPTER 1

Table 1.4 Four cardinal signs of acute inflammation were first described by Celsus in about 25 B.C. as the
acute inflammation according to cardinal signs of acute inflammation (Table 1.4). The signs of inflammation
Celsus (25 B.C.)a
are manifestations of increased blood flow and infiltration of tissues by in-
Latin English flammatory proteins and cells. Increased blood flow causes redness and
increased temperature. The presence of fluid and red blood cells in tissues
Rubor Redness
is grossly recognized by swelling (edema) and redness. White blood cell
Tumor Swelling
(inflammatory cell) infiltrations cause a white color. If the site of inflam-
Calor Heat
mation is necrotic and filled with white blood cells, the inflammatory site
Dolor Pain
will be seen as pus. If red blood cells are present, the pus may be yellow
a
The fifth classic sign of acute inflammation, or bloody red, depending on the proportion of red cells. The cellular evo-
“functio laesa” (loss of function), was added by
Rudolf Virchow (1821–1902). lution of an inflammatory response eventually results in the healing or
scarring of the lesion.

Immunopathology (the Double-Edged Sword)

The immune system did not evolve without ambivalence and flaws. The
same system that functions so well to protect against foreign invaders
may also turn against us. The term immunopathology is a misnomer: “im-
mune” means protection or exemption from; “pathology” is the study of
disease. Thus, immunopathology literally means the study of the protec-
tion from disease, but in usage it actually means the study of how im-
mune mechanisms cause diseases. Immunity is a double-edged sword: on
one hand, immune responses protect us from infections; on the other
hand, immune mechanisms may cause disease. The most compelling evi-
dence that immune reactions are protective is provided by the naturally
occurring immune deficiency diseases. Individuals with an inability to
mount an effective immune response to infectious agents invariably suc-
cumb to infections unless they are vigorously treated. However, immune
reactions may also cause disease. The terms allergy and hypersensitivity
are used to denote deleterious immune reactions. Allergy is frequently
used for a particular type of rapidly developing explosive immune reac-
tion (anaphylactic), and hypersensitivity is used for delayed-type or cell-
mediated immune reactivity. The term immunity was once restricted to
the protective effects of immune reactions, but by common usage this is
no longer the case. In some diseases, immune mechanisms may actually
be directed against our own tissues. This is termed autoimmunity.
How the immune system coordinates the process of inflammation,
both in protection and in causing disease (immune effector mechanisms),
is the focus of this book. Immune effector mechanisms are essentially vari-
ations of the inflammatory response influenced by specific products of the
adaptive immune system. Therefore, before we can address these mecha-
nisms and their effects, it is necessary to understand the basics of inflam-
mation and immunology; these are covered in part I of this book.

Summary
Immunology is the study of how we protect ourselves against infection.
The seemingly unlimited variations in the way that infectious agents can
invade and colonize our bodies necessitates a counterbalancing system of
defense that employs many different strategies. One system is constitu-
tive and consists of mechanical barriers, pH, temperature, phagocytosis,
inflammation, and so on (innate resistance). The other is induced and
consists of specific products that recognize invaders as foreign (adaptive
 Introduction to Part I 9

immunity). After induction (immunization), the adaptive system re-

sponds more rapidly and with greater intensity than after first exposure
(immune memory). The two major arms of the adaptive immune re-
sponse are humoral (antibody) and cellular (specifically sensitized cells).
Specialized cells of the body known as lymphocytes are responsible for
the adaptive immune response (T lymphocytes for cellular immunity and
B lymphocytes for humoral immunity). In response to infection, both
adaptive and innate inflammatory mechanisms may be activated. During
evolution, the adaptive immune response became increasingly complex.
Humans have different classes of antibody and different subsets of T cells
that not only have different functions as immune effectors but also are
able to direct and modify inflammatory events to provide specific direc-
tion to appropriate combinations of inflammatory events in order to com-
bat many different infectious agents.
The immune response is not always protective; in many instances, the
same immune effector mechanisms that defend us against foreign in-
vaders may be turned against us and produce disease (the double-edged
sword of immunopathology). Part I of this book (Immunology) describes
the basics of the inflammatory and immune response systems. Part II (Im-
munopathology and Immunity) explains how the same immune mecha-
nisms are used for both destruction and defense.

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