Immunity and Allergy pdf - Blood Cells and Immunity and Blood Clotting

that would be lethal without immunity. This is the reason the treatment process

tetanus, can be protected against in doses as high as 100,000 times the amount

certain toxins, such as the paralytic botulinum toxin or the tetanizing toxin of

Acquired immunity can often bestow extreme protection. For instance,

phocytes that attack and destroy the specific invading organism or toxin. It is

. Acquired immunity is

animals. This is called

agents such as lethal bacteria, viruses, toxins, and even foreign tissues from other

In addition to its generalized innate immunity, the human body has the ability

Acquired (Adaptive) Immunity

and syphilis, which are very damaging or even lethal to human beings.

to many human diseases, such as poliomyelitis, mumps, human cholera, measles,

afflicted with it. Conversely, many lower animals are resistant or even immune

some paralytic viral infections of animals, hog cholera, cattle plague, and dis-

This innate immunity makes the human body resistant to such diseases as

even some infected cells.

that can recognize and destroy foreign cells, tumor cells, and

activated in various ways to destroy bacteria; and (4)

that is described later, a system of about 20 proteins that can be

inactivate certain types of gram-positive bacteria; (3) the

, which react with and

causes them to dissolute; (2)

, a mucolytic polysaccharide that attacks bacteria and

foreign organisms or toxins and destroy them. Some of these compounds

4. Presence in the blood of certain chemical compounds that attach to

3. Resistance of the skin to invasion by organisms.

and the digestive enzymes.

2. Destruction of swallowed organisms by the acid secretions of the stomach

of the tissue macrophage system, as described in Chapter 33.

1. Phagocytosis of bacteria and other invaders by white blood cells and cells

innate immunity.

at specific disease organisms. This is called

immunity results from general processes, rather than from processes directed

requiring weeks or months to develop the immunity. An additional portion of

attacked by a bacterium, virus, or toxin, often

nity.

tissues and organs. This capability is called

The human body has the ability to resist almost all

Infection: II. Immunity and Allergy

439

Resistance of the Body to

Innate Immunity

types of organisms or toxins that tend to damage the

immu-

Much of immunity is acquired immunity that

does not develop until after the body is first

It includes the

following:

are (1) lysozyme

basic polypeptides

complement

complex

natural killer

lymphocytes

temper—a viral disease that kills a large percentage of dogs that become

to develop extremely powerful specific immunity against individual invading

acquired or adaptive immunity

caused by a special immune system that forms antibodies and/or activated lym-

with this acquired immunity mechanism and some of its associated reactions—
especially the allergies—that this chapter is concerned.

known as immunization is so important in protecting human beings against

of the embryo, these

lymphocyte-committed stem cells

Although all lymphocytes in the body originate from

Lymphocytes

Preprocessing of the T and B

cytes and (2) the antibodies.

mation, respectively, of (1) the activated T lympho-

34–1 shows the two lymphocyte systems for the for-

they are responsible for humoral immunity. Figure

to designate the role of the bursa, and

. For this reason, these lymphocytes are called

bursa of Fabri-

ulation of cells was first discovered in birds, which have

bone marrow in late fetal life and after birth. This pop-

phocytes that are destined to form antibodies—are

The other population of lymphocytes—the B lym-

immunity.

the thymus. They are responsible for cell-mediated

“T” lymphocytes

gland, and thus they are

form activated T lymphocytes first migrate to and are

The lymphocytes that are destined to eventually

differentiated or “preprocessed” in the following ways.

lymphoid tissue, but before doing so, they are further

phocytes that are formed eventually end up in the

offspring as they differentiate. Almost all of the lym-

that form lymphocytes as one of their most important

pluripotent hematopoietic stem cells

Both types of lymphocytes are derived originally in

immunity.

for forming antibodies that provide “humoral”

other population, the B lymphocytes, is responsible

cytes that provide “cell-mediated” immunity, and the

cytes, is responsible for forming the activated lympho-

populations. One of the populations, the T lympho-

tissue look alike when studied under the microscope,

Although most lymphocytes in normal lymphoid

or “Humoral” Immunity—the T and the B Lymphocytes.

Two Types of Lymphocytes Promote “Cell-Mediated” Immunity

the spleen, thymus, and bone marrow plays the specific

tissues of the body. And, finally, the lymphoid tissue of

piratory tract. The lymphoid tissue in the lymph nodes

from the gut. The lymphoid tissue of the throat and

instance, the lymphoid tissue of the gastrointestinal

to the lymph node or other lymphoid tissue. For

In most instances, the invading agent first enters the

before they can spread too widely.

The lymphoid tissue is distributed advantageously in

bone marrow

, and

, but they are also found in special lym-

The lymphocytes are located most extensively in the

phocytes are essential to survival of the human being.

by heroic measures. Therefore, it is clear that the lym-

develop. And within days after birth, such a person

by radiation or chemicals, no acquired immunity can

phocytes or whose lymphocytes have been destroyed

phocytes. In people who have a genetic lack of lym-

Acquired immunity is the product of the body’s lym-

Lymphocytes Are Responsible for

eochemical characteristic.

always antigenic, because both of these have this ster-

the surface of the large molecule. This also explains

epitopes,

larly recurring molecular groups, called

a high molecular weight, 8000 or greater. Furthermore,

For a substance to be antigenic, it usually must have

ate the acquired immunity. These substances are called

teins or large polysaccharides, and it is they that initi-

from all other compounds. In general, these are pro-

nizing this invasion. Each toxin or each type of organ-

after invasion by a foreign organism or toxin, it is clear

Initiated by Antigens

Both Types of Acquired Immunity Are

antigens.

phoid tissues of the body. Let us discuss the initiation

and the activated lymphocytes are formed in the lym-

cytes). We shall see shortly that both the antibodies

(because the activated lymphocytes are T lympho-

T-cell immunity

cell-mediated immunity

destroy the foreign agent. This type of immunity is

activated T lymphocytes

B lymphocytes produce the antibodies). The second

attacking the invading agent. This type of immunity is

antibodies,

nity occur in the body. In one of these the body

Two basic but closely allied types of acquired immu-

Basic Types of Acquired Immunity

of this chapter.

disease and against toxins, as explained in the course

Blood Cells, Immunity, and Blood Clotting

440

Unit VI

develops circulating

which are globulin

molecules in the blood plasma that are capable of

called humoral immunity or B-cell immunity (because

type of acquired immunity is achieved through the
formation of large numbers of
that are specifically crafted in the lymph nodes to

called

of the immune process by

Because acquired immunity does not develop until

that the body must have some mechanism for recog-

ism almost always contains one or more specific
chemical compounds in its makeup that are different

antigens (antibody generations).

the process of antigenicity usually depends on regu-

why proteins and large polysaccharides are almost

Acquired Immunity

dies of fulminating bacterial infection unless treated

lymph nodes
phoid tissues such as the spleen, submucosal areas of

the gastrointestinal tract, thymus

the body to intercept invading organisms or toxins

tissue fluids and then is carried by way of lymph vessels

walls is exposed immediately to antigens invading

pharynx (the tonsils and adenoids) is well located to
intercept antigens that enter by way of the upper res-

is exposed to antigens that invade the peripheral

role of intercepting antigenic agents that have suc-
ceeded in reaching the circulating blood.

these cells are distinctly divided into two major

the embryo from

preprocessed in the thymus
called

to designate the role of

preprocessed in the liver during midfetal life and in the

a special preprocessing organ called the
cius

“B”

lymphocytes

areas.

near but slightly removed from the T-lymphocyte

phoid tissue throughout the body, where they lodge

lymphocytes, like the T lymphocytes, migrate to lym-

ferent specific reactivities. After preprocessing, the B

millions of types of B-lymphocyte antibodies with dif-

diversity than the T lymphocytes, thus forming many

33. Second, the B lymphocytes have even greater

and destroying the antigenic substance, which is

that are the reactive agents. These agents are large

phocytes, the B lymphocytes actively secrete

reactivity against the antigen, as occurs for the T lym-

two ways: First, instead of the whole cell developing

B lymphocytes are different from T lymphocytes in

the human being, B lymphocytes are known to be pre-

lymphocytes than for preprocessing T lymphocytes. In

Liver and Bone Marrow Preprocess the B Lymphocytes.

kidneys, one can transplant organs with much less like-

rejection of transplanted organs, such as hearts and

development of all cell-mediated immunity. Because

the T-lymphocytic immune system. However, removal

few months after birth. Beyond this period, removal of

Most of the preprocessing of T lymphocytes in the

a toxin, or even transplanted tissue from another

gens from an outside source, such as from a bacterium,

the body’s own antigens—they react only against anti-

90 per cent of the cells. Thus, the only cells that are

instead of being released. This happens to as many as

lymphocyte reacts, it is destroyed and phagocytized

cific “self-antigens” from the body’s own tissues. If a T

The thymus selects which T lymphocytes will be

lethal to the person’s own body in only a few days.

own tissues; otherwise, the T lymphocytes would be

or other antigens that are present in the body’s

cytes leaving the thymus will not react against proteins

The thymus also makes certain that any T lympho-

to lodge in lymphoid tissue everywhere.

preprocessed T lymphocytes now leave the thymus

sands of different antigens. These different types of

phocytes with specific reactivities against many thou-

ficity against another antigen. This continues until

one antigen. Then the next lymphocyte develops speci-

thymic lymphocyte develops specific reactivity against

reacting against different specific antigens. That is, one

migrate to the thymus gland. Here they divide rapidly

phocytes, after origination in the bone marrow, first

The T lym-

Thymus Gland Preprocesses the T Lymphocytes.

appropriate processing areas as follows.

they can do so, they must be further differentiated in

either activated T lymphocytes or antibodies. Before

Resistance of the Body to Infection: II. Immunity and Allergy

Chapter 34

441

stem cells themselves are incapable of forming directly

and at the same time develop extreme diversity for

there are thousands of different types of thymic lym-

and spread by way of the blood throughout the body

released by first mixing them with virtually all the spe-

finally released are those that are nonreactive against

person.

thymus occurs shortly before birth of a baby and for a

the thymus gland diminishes (but does not eliminate)

of the thymus several months before birth can prevent

this cellular type of immunity is mainly responsible for

lihood of rejection if the thymus is removed from an
animal a reasonable time before its birth.

Much

less is known about the details for preprocessing B

processed in the liver during midfetal life and in the
bone marrow during late fetal life and after birth.

antibod-

ies
protein molecules that are capable of combining with

explained elsewhere in this chapter and in Chapter

T lymphocytes

Thymus

Cell-Mediated Immunity

Humoral Immunity

Antigen

Activated T

lymphocytes

Antigen

Antibodies

Plasma

cells

B lymphocytes

Fetal liver,

bone marrow

Stem cell

Lymph node

and humoral immune processes.

responsible for the cell-mediated

phocytes that respectively are

This figure also shows the origin

node in response to antigens.

Formation of antibodies and sen-

Figure 34–1

sitized lymphocytes by a lymph

of thymic (T) and bursal (B) lym-

immunity.

to describe the mechanisms of the T-cell system of

this cooperative relationship between helper T cells

by the B lymphocytes is usually slight. We will discuss

these helper T cells, the quantity of antibodies formed

specific B lymphocytes. Indeed, without the aid of

, secrete specific substances

formed, called

cytes at the same time. Some of the T cells that are

antigens activate both T lymphocytes and B lympho-

Role of the T Cells in Activation of the B Lymphocytes.

reproduction of the specific lymphocytes. This sub-

macrophages, in addition, secrete a special activating

activation of the specified lymphocytic clones. The

contact directly to the lymphocytes, thus leading to

ucts are liberated into the macrophage cytosol. The

digested by the macrophages, and the antigenic prod-

ing organisms are first phagocytized and partially

to many of the lymph node lymphocytes. Most invad-

and other lymphoid tissue, and they lie in apposition

These line the sinusoids of the lymph nodes, spleen,

of macrophages are also present in the same tissue.

the lymphocytes in lymphoid tissue, literally millions

the surface of the T-cell membrane, and these, too,

), are on

T-cell markers

lymphocytes, molecules similar to antibodies, called

in more detail subsequently. In the case of the T

this leads to the activation process, which we describe

the appropriate antigen comes along, it immediately

only one specific type of antigen. Therefore, when

the case of the B lymphocytes, each of these has on the

characteristics). The reason for this is the following: In

Each clone of lymphocytes is responsive to only a

of Lymphocytes

spread to and populate the lymphoid tissue.

then become the highly specific T and B cells that

for only a single antigen specificity. These mature cells

phocyte that is finally formed, the gene structure codes

types that can occur. For each functional T or B lym-

in which the segments can be arranged in single cells,

segments, as well as millions of different combinations

Because there are several hundred types of gene

whole genes.

in random combinations, in this way finally forming

cessing of the respective T- and B-cell lymphocytes,

such segments—but not whole genes. During prepro-

there are only “gene segments”—actually, hundreds of

which the functional immune cells are formed. Instead,

The whole gene for forming each type of T cell or B

protein. This mystery has now been solved.

can be produced by the lymphoid tissue, especially

ferent specificities of antibody molecules or T cells that

lymphocytes. At first, it was a mystery how it was pos-

for the millions of different types of antibodies and T

of Lymphocytes

Origin of the Many Clones

one or a few early lymphocytes of its specific type.

. That is, the lymphocytes in

forming one specificity of antibody or T cell are called

All the different lymphocytes that are capable of

around in this circuit for months or years.

into the lymph, sometimes circulating around and

its progeny are specific sensitized T cells that are

circulates throughout the body. If it is a T lymphocyte,

cytes. If it is a B lymphocyte, its progeny will eventu-

phocyte is activated by its antigen, it reproduces wildly,

which it can react can activate it. Once the specific lym-

specificity. And only the specific type of antigen with

antibody or one type of T cell with a single type of

lymphocytes is capable of forming only one type of

tissue, as explained earlier. Each of these preformed

antibodies or T cells have been stored in the lymph

formed B lymphocytes and preformed T lymphocytes

Lymphoid Tissue.

Millions of Specific Types of Lymphocytes Are Stored in the

following.

opment. The mechanism of this specificity is the

vated to form antibodies. The activated T cells and

cells, and certain of the B lymphocytes become acti-

lymphocytes become activated to form activated T

lymphocytes in the lymphoid tissue, certain of the T

When specific antigens come in contact with T and B

Lymphocyte Clones

Against Specific Antigens—Role of

T Lymphocytes and B-Lymphocyte

Blood Cells, Immunity, and Blood Clotting

442

Unit VI

Antibodies React Highly Specifically

antibodies in turn react highly specifically against the
particular types of antigens that initiated their devel-

Millions of different types of pre-

that are capable of forming highly specific types of

forming tremendous numbers of duplicate lympho-

ally secrete the specific type of antibody that then

released into the lymph and then carried to the blood
and circulated through all the tissue fluids and back

a clone of lymphocytes
each clone are alike and are derived originally from

Only several hundred to a few thousand genes code

sible for so few genes to code for the millions of dif-

when one considers that a single gene is usually nec-
essary for the formation of each different type of

cell is never present in the original stem cells from

these gene segments become mixed with one another

one can understand the millions of different cell gene

Mechanism for Activating a Clone

single type of antigen (or to several similar antigens
that have almost exactly the same stereochemical

surface of its cell membrane about 100,000 antibody
molecules that will react highly specifically with

attaches to the antibody in the cell membrane;

surface receptor proteins (or

are highly specific for one specified activating
antigen.

Role of Macrophages in the Activation Process.

Aside from

macrophages then pass these antigens by cell-to-cell

substance that promotes still further growth and

stance is called interleukin-1.

Most

helper cells

(collectively called lymphokines) that activate the

and B cells again after we have an opportunity

other biological properties of the antibody.

which the antibodies pass through membranes, and

, the ease with

the antibody to specific structures within the tissues,

diffusivity of the antibody in the tissues, adherence of

properties of the antibody, establishing such factors as

attaches specifically to a particular type of antigen. The

specificity of antibody, and it is this portion that

. The variable portion is different for each

; the remainder of each chain is called the

end of each light and heavy chain, called the

Figure 34–3 shows by the circled area a designated

such pairs in each immunoglobulin molecule.

pair, and there are always at least 2 and as many as 10

light chain at one of its ends, thus forming a heavy-light

immunoglobulins, each heavy chain is paralleled by a

high-molecular-weight immunoglobulins. Yet, in all

10 heavy and 10 light chains, which gives rise to

as shown in Figure 34–3. However, some of the

a combination of two light and two heavy chains,

. Most are

heavy polypeptide chains

constitute about 20 per cent of all the plasma proteins.

lar weights between 160,000 and 970,000. They usually

), and they have molecu-

The antibodies are gamma globulins called

Nature of the Antibodies

injections.

increased potency and duration of the secondary

many months rather than for only a few weeks. The

hours), is far more potent, and forms antibodies for

life. The secondary response, by contrast, begins

the primary response, its weak potency, and its short

antigen. Note the 1-week delay in the appearance of

Figure 34–2 shows the differences between the

of the specific clone.

memory cells than there were original B lymphocytes

second time around, because there are many more

. Subsequent

lymphocytes are called

again by a new quantity of the same antigen. These

however, they remain dormant until activated once

populate all the lymphoid tissue; immunologically,

same clone. They also circulate throughout the body to

cytes are added to the original lymphocytes of the

becomes greatly enhanced, and the new B lympho-

to those of the original clone. In other words, the B-

form moderate numbers of new B lymphocytes similar

phocytes do not go on to form plasma cells but instead

Response and Secondary Response.

Formation of “Memory” Cells—Difference Between Primary

occur.

blood.This process continues for several days or weeks

second for each plasma cell. In turn, the antibodies are

cells for each original plasmablast. The mature plasma

sions, giving in 4 days a total population of about 500

proliferates. The plasmablasts then begin to divide at

. In the plasmablasts, the cytoplasm

, which are precursors

. Some of the lymphoblasts further dif-

Those B lymphocytes specific for the antigen imme-

more fully later.

extreme activation of the B lymphocytes, as we discuss

are formed. These helper cells also contribute to

T cells at the same time, and activated helper T cells

B lymphocytes. In addition, the antigen is presented to

phagocytize the antigen and then present it to adjacent

foreign antigen, macrophages in the lymphoid tissue

remain dormant in the lymphoid tissue. On entry of a

to a specific antigen, the clones of B lymphocytes

Immunity and the Antibodies

B-Lymphocyte System—Humoral

Specific Attributes of the

Resistance of the Body to Infection: II. Immunity and Allergy

Chapter 34

443

Formation of Antibodies by Plasma Cells.

Before exposure

diately enlarge and take on the appearance of
lymphoblasts
ferentiate to form plasmablasts
of plasma cells
expands and the rough endoplasmic reticulum vastly

a rate of about once every 10 hours for about nine divi-

cell then produces gamma globulin antibodies at an
extremely rapid rate—about 2000 molecules per

secreted into the lymph and carried to the circulating

until finally exhaustion and death of the plasma cells

A few of the lym-

phoblasts formed by activation of a clone of B lym-

cell population of the specifically activated clone

memory cells

exposure to the same antigen will cause a much more
rapid and much more potent antibody response this

primary response for forming antibodies that occurs on
first exposure to a specific antigen and the secondary
response that occurs after second exposure to the same

rapidly after exposure to the antigen (often within

response explain why immunization is usually accom-
plished by injecting antigen in multiple doses with
periods of several weeks or several months between

immuno-

globulins (abbreviated as Ig

All the immunoglobulins are composed of combi-

nations of light and

immunoglobulins have combinations of as many as

variable

portion

con-

stant portion

constant portion of the antibody determines other

attachment to the complement complex

Weeks

Concentration of antibody

128

Secondary

Primary

months later.

secondary

primary

Time course of the antibody response in the circulating blood to

Figure 34–2

injection of antigen and to a

injection several

normal person, and IgE, which constitutes only a small

importance: IgG, which is a bivalent antibody and con-

For the purpose of our present limited discussion,

five respective letters designate the respective classes.

. Ig stands for immunoglobulin, and the other

IgM, IgG, IgA, IgD,

antibodies, respectively named

There are five general classes of

sites.

chains, have as many as 10

. A small proportion of the antibodies, which

ment of antigens, making this type of antibody

Note, especially, in Figure 34–3 that there are two

law.

forces. It also obeys the thermodynamic mass action

bonding, (3) ionic attractions, and (4) van der Waals

together by (1) hydrophobic bonding, (2) hydrogen

antibody-antigen coupling is exceedingly strong, held

highly specific, there are so many bonding sites that the

the antibody and the antigen. When the antibody is

body, thus allowing rapid and tight bonding between

antigen fit as a mirror image with those of the anti-

contact with it, multiple prosthetic groups of the

antigen specificity, so that when an antigen comes in

tions of both the light and heavy chains. The amino

particular antigen; this is caused by its unique struc-

Blood Cells, Immunity, and Blood Clotting

444

Unit VI

Specificity of Antibodies.

Each antibody is specific for a

tural organization of amino acids in the variable por-

acid organization has a different steric shape for each

is called the affinity constant and is a measure of

how tightly the antibody binds with the antigen.

variable sites on the illustrated antibody for attach-

biva-

lent
consist of combinations of up to 10 light and 10 heavy

binding

Classes of Antibodies.

and IgE

two of these classes of antibodies are of particular

stitutes about 75 per cent of the antibodies of the

percentage of the antibodies but is especially involved

Concentration of bound antibody-antigen

Concentration of antibody

Concentration of antigen

major role in protecting the body against the invader.

These direct actions of antibodies attacking the anti-

, in which some potent antibodies are

Lysis

, in which the antibodies cover the

, in which the molecular complex of

red cells, are bound together into a clump

with antigens on their surfaces, such as bacteria or

, in which multiple large particles

agent in one of several ways, as follows:

ing agents, the antibodies can inactivate the invading

objects). Because of the bivalent nature of the anti-

shows antibodies (designated by the red Y-shaped

Figure 34

destroying the invader.

against invading agents: (1) by direct attack on the

though there are not many IgM antibodies.

effective in protecting the body against invaders, even

primary response are of this type. These antibodies

in allergy. The IgM class is also interesting because
a large share of the antibodies formed during the

have 10 binding sites that make them exceedingly

Mechanisms of Action of Antibodies

Antibodies act mainly in two ways to protect the body

invader and (2) by activation of the “complement
system” that then has multiple means of its own for

Direct Action of Antibodies on Invading Agents.

–4

bars) reacting with antigens (designated by the shaded

bodies and the multiple antigen sites on most invad-

1. Agglutination

2. Precipitation

soluble antigen (such as tetanus toxin) and
antibody becomes so large that it is rendered
insoluble and precipitates

3. Neutralization

toxic sites of the antigenic agent

occasionally capable of directly attacking
membranes of cellular agents and thereby cause
rupture of the agent

genic invaders often are not strong enough to play a

Most of the protection comes through the amplifying
effects of the complement system described next.

Antigen-binding sites

Antigen

Light

chain

Heavy

chain

Constant portion

Variable portion

S • S
S • S

S • S

The antigen binds at two different sites on the variable portions of

Structure of the typical IgG antibody, showing it to be composed

Figure 34–3

of two heavy polypeptide chains and two light polypeptide chains.

the chains.

Antigen

Antibodies

Figure 34–4

Binding of antigen molecules to one another by bivalent
antibodies.

immobilize the antigenic agent. The same factors

uid and plasma protein into the tissue, and other

ow, increased leakage of

uids. These substances in turn cause

heparin, and several other substances into the

basophils, causing them to release histamine,

C3a, C4a, and C5a activate mast cells and

Fragments

Activation of mast cells and basophils.

numbers of these phagocytes to migrate into the

neutrophils and macrophages, thus causing large

Fragment C5a initiates chemotaxis of

Chemotaxis.

The complement

Neutralization of viruses.

causing them to adhere to one another, thus

change the surfaces of the invading organisms,

The complement products also

organisms.

This has a direct effect of rupturing the cell

, which is a combination of multiple

Lysis.

. It often enhances the number

antibody complexes are attached. This process is

neutrophils and macrophages, causing these cells

strongly activates phagocytosis by both

products of the complement cascade, C3b,

Opsonization and phagocytosis.

toxin. Among the more important effects are the

gure, and several of these cause

occurs. Multiple end products are formed, as shown to

beginning, an extremely large

the later stages of the system, so that from a small

zyme C1 itself. The C1 enzymes that are formed then

5, beginning with activation of the proen-

in Figure 34

of sequential reactions, shown

the C1 molecule of the complement system, setting

ered, or

binds with an antigen, a speci

antigen-antibody reaction. That is, when an antibody

The classic pathway is initiated by an

Classic Pathway.

classic pathway.

spaces. The enzyme precursors are normally inactive,

5. All these are present normally among

in Figure 34

proteins designated C1 through C9, B, and D, shown

precursors. The principal actors in this system are 11

system of about 20 proteins, many of which are enzyme

Resistance of the Body to Infection: II. Immunity and Allergy

Chapter 34

445

Complement System for Antibody Action

“Complement” is a collective term that describes a

–

the plasma proteins in the blood as well as among the
proteins that leak out of the capillaries into the tissue

but they can be activated mainly by the so-called

fic reactive site on the

“constant” portion of the antibody becomes uncov-

“activated,” and this in turn binds directly with

into motion a “cascade”

–

activate successively increasing quantities of enzymes in

“amplified” reaction

the right in the fi
important effects that help to prevent damage to the
body’s tissues caused by the invading organism or

following:
1.

One of the

to engulf the bacteria to which the antigen-

called opsonization
of bacteria that can be destroyed by many
hundredfold.

One of the most important of all the

products of the complement cascade is the lytic
complex
complement factors and designated C5b6789.

membranes of bacteria or other invading

3. Agglutination.

promoting agglutination.

enzymes and other complement products can
attack the structures of some viruses and thereby
render them nonvirulent.

tissue area adjacent to the antigenic agent.

local fl
increased local blood fl
fl
local tissue reactions that help inactivate or

play a major role in inflammation (which was

C6 + C7

C5b67

C4 + C2

C42 + C4a

Antigen–antibody complex

Micro-organism +

B and D

Opsonization of bacteria

Activate mast
cells and basophils

Chemotaxis of
white blood cells

C3b + C3a

C8 + C9

C5b + C5a

C5b6789

Lysis of cells

mentals of Clinical Immunology.

Alexander JW, Good RA: Funda-

of complement. (Modified from

Cascade of reactions during

Figure 34–5

activation of the classic pathway

Philadelphia: WB Saunders,
1977.)

T cells, usually constituting more than three quarters

The helper T cells are by far the most numerous of the

. The functions of each of these are distinct.

, and (3)

cytotoxic T cells

, (2)

helper T cells

ed into three major groups: (1)

cells. They are classi

It has become clear that there are multiple types of T

Several Types of T Cells and Their

There are as many as 100,000 receptor sites on a single

bound to the cell membrane of the T lymphocyte.

of the humoral antibody, but its stem section is

protein antibodies. These receptor molecules are com-

on the surfaces of T

The antigens on the surface of antigen-presenting

helper T cells are discussed later.

c functions of cytotoxic and

. The speci

, which present antigens

, and (2)

cytotoxic T

, which present antigens to

surface. There are two types of MHC proteins: (1)

. The MHC proteins bind peptide fragments

The MHC proteins are encoded by a large group of

is critical in permitting the T cells to bind

to present antigens to T cells. Interaction of

throughout the body, and their only known function is

potent of the antigen-presenting cells, are located

. The dendritic cells, the most

, and

6). The three major types of

tissues (Figure 34

T lymphocytes respond to antigens only when they are

Although B lymphocytes recognize intact antigens,

ally helping to eliminate invading pathogens.

begin the process, and T cells play a major role in actu-

responses usually require assistance from T cells to

fending against infection. In fact, acquired immune

c, like the antibody responses of B cells,

T-cell responses are extremely

tors on the T Lymphocytes.

rst exposure.

in the body, release of activated T cells occurs far more

out the lymphoid tissue of the entire body. Therefore,

clone; in fact, these memory cells even spread through-

become additional T lymphocytes of that speci

lymphocytes are preserved in the lymphoid tissue to

activated by an antigen, many of the newly formed

body system. That is, when a clone of T lymphocytes is

T-lymphocyte memory cells

Also,

body, sometimes lasting for months or even years.

again, and circulating again and again throughout the

the tissue spaces, back into the lymph and blood once

out the body, passing through the capillary walls into

are formed and released into the lymph. These then

instead of releasing antibodies, whole activated T cells

activated B cells. The principal difference is that

ing T cells in ways that parallel antibody release by

release large numbers of activated, speci

c lymphocyte clone proliferate and

cytes of a speci

as presented by adjacent macrophages, the T lympho-

tion of Memory Cells.

Release of Activated T Cells from Lymphoid Tissue and Forma-

T Cells and Cell-Mediated Immunity

T-Lymphocyte System

Special Attributes of the

organism through the tissues.

uid proteins to coagulate in the tissue spaces,

proteins to be increased, and (3) the interstitial

increase still further, (2) the capillary leakage of

ammation. These products

basophils, several other complement products

Inflammatory effects.

discuss later.

discussed in Chapter 33) and in allergy, as we

Blood Cells, Immunity, and Blood Clotting

446

Unit VI

In addition to inflammatory

effects caused by activation of the mast cells and

contribute to local infl
cause (1) the already increased blood flow to

fl
thus preventing movement of the invading

–Activated

On exposure to the proper antigen,

fically react-

pass into the circulation and are distributed through-

are formed in the

same way that B memory cells are formed in the anti-

fic

on subsequent exposure to the same antigen anywhere

rapidly and much more powerfully than had occurred
during fi

Antigen-Presenting Cells, MHC Proteins, and Antigen Recep-

antigen specifi
and are at least as important as antibodies in de-

bound to specific molecules called MHC proteins on
the surface of antigen-presenting cells in the lymphoid

–

antigen-presenting cells are macrophages, B lympho-
cytes

dendritic cells

cell adhe-

sion proteins
to antigen-presenting cells long enough to become
activated.

genes called the major histocompatibility complex
(MHC)
of antigen proteins that are degraded inside antigen-
presenting cells and then transport them to the cell

MHC I proteins
cells

MHC II proteins

to T helper cells

cells bind with receptor molecules
cells in the same way that they bind with plasma

posed of a variable unit similar to the variable portion

firmly

T cell.

Different Functions

suppressor

T cells

Helper T Cells—Their Role in Overall
Regulation of Immunity

Cell-cell

adhesion

proteins

T-cell receptor

Foreign protein

MHC protein

T cell

Antigen-
presenting
cell

to bind to the antigen-presenting cell long enough to become

(MHC) protein. Cell-to-cell adhesion proteins enable the T cell

antigen-presenting cell by a major histocompatibility complex

antigen (foreign protein) that is transported to the surface of the

Activation of T cells requires interaction of T-cell receptors with an

Figure 34–6

activated.

punched holes and delivered cytotoxic substances and

Especially important, these cytotoxic killer cells can

swollen, and it usually dissolves shortly thereafter.

Almost immediately, the attacked cell becomes greatly

cytotoxic substances directly into the attacked cell.

tial space. In addition, the cytotoxic T cell releases

Then

, that literally punch

, called

After binding, the cytotoxic T cell secretes

the attacked cell in the manner shown in Figure 34

c antigen. Then, they kill

surfaces of the cytotoxic cells cause them to bind

. The receptor proteins on the

s own cells. For this reason, these

capable of killing micro-organisms and, at times, even

The cytotoxic T cell is a direct-attack cell that is

This acts as an ampli

stimulating activation of the helper T cells themselves.

leukin-2, have a direct positive feedback effect in

Some of the lymphokines, especially inter-

bacteria or other tissue-destroying agents.

cient phagocytosis, allowing them

macrophages. Second, they activate the macrophages

tissue area, thus causing great accumulation of

phokines also affect the macrophages. First, they slow

The lym-

Activation of the Macrophage System.

B-cell growth factors

response, but especially interleukins 4, 5, and 6. In fact,

of the helper T cells.

mation of plasma cells, and secretion of antibodies are

of antigen to cause B-cell growth, proliferation, for-

The direct actions

Form Plasma Cells and Antibodies.

Stimulation of B-Cell Growth and Differentiation to

potent effects.

In addition, several of the other lymphokines have less

proliferation of both cytotoxic and suppressor T cells.

antigens. The lymphokine

suppressor T cells are activated only slightly by most

T cells, the clones for producing cytotoxic T cells and

Stimulation of Growth and Proliferation of Cytotoxic T

functions are the following.

lethal effects of AIDS. Some of the speci

totally unprotected against infectious disease, there-

, which leaves the body almost

lyzed. In fact, it is the helper T cells that are inactivated

absence of the lymphokines from the helper T cells,

Specific Regulatory Functions of the Lymphokines.

Granulocyte-monocyte colony-stimulating factor

helper T cells are the following:

immune system as well as on bone marrow cells.

lymphokines,

ators, called

7. They do this by forming a series of protein medi-

of virtually all immune functions, as shown in Figure

many ways. In fact, they serve as the major regulator

functions of the immune system, and they do so in

of all of them. As their name implies, they

Resistance of the Body to Infection: II. Immunity and Allergy

Chapter 34

447

help in the

34–

that act on other cells of the

Among the important lymphokines secreted by the

Interleukin-2
Interleukin-3
Interleukin-4
Interleukin-5
Interleukin-6

Interferon-

In the

the remainder of the immune system is almost para-

or destroyed by the acquired immunodeficiency syn-
drome (AIDS) virus

fore leading to the now well-known debilitating and

fic regulatory

Cells and Suppressor T Cells.

In the absence of helper

interleukin-2 has an espe-

cially strong stimulatory effect in causing growth and

also slight without the “help”
Almost all the interleukins participate in the B-cell

these three interleukins have such potent effects on
the B cells that they have been called B-cell stimulat-
ing factors or

or stop the migration of the macrophages after they
have been chemotactically attracted into the inflamed

to cause far more effi
to attack and destroy increasing numbers of invading

Feedback Stimulatory Effect on the Helper Cells Them-
selves.

fier by further enhancing the

helper cell response as well as the entire immune
response to an invading antigen.

Cytotoxic T Cells

some of the body’
cells are called killer cells

tightly to those organisms or cells that contain the
appropriate binding-specifi

–8.

hole-

forming proteins

perforins

round holes in the membrane of the attacked cell.

fluid flows rapidly into the cell from the intersti-

pull away from the victim cells after they have

Preprocessor

areas

Lymphokines!!

Antigen

Processed

antigen

MHC

B cell

Suppressor

T cells

Plasma

cells

Cytotoxic

T cells

Helper
T cells

Antigen-specific receptor

Differentiation

Proliferation

IgM

IgG

IgA

IgE

Preprocessor

areas

Interleukin-1

Regulation of the immune system, emphasizing a pivotal role of

Figure 34–7

the helper T cells. MHC, major histocompatibility complex.

immunization is used to protect against typhoid fever,

still have some of their chemical antigens. This type of

c diseases. A

Immunization by Injection of Antigens

same time, a disease that causes extensive damage and

, in which the person becomes

the neuromuscular junction, causing paralysis; and (4)

, in which immunity

glomeruli; (3)

, in which the person becomes

s own self-antigens; (2) one type of

heart, especially the heart valves, after exposure to a

, in which the body

antibodies.

immunity in the form of either activated T cells or

s own tissues, which releases

older a person becomes. It usually occurs after destruc-

of their own tissues. This occurs to a greater extent the

Failure of the Tolerance Mechanism Causes Autoimmune Dis-

antigens.

of those clones of lymphocytes that are speci

phocytes in the thymus and bone marrow, all or most

the total body lymphoid tissue.

proliferate considerably, and then combine with the

exposed to a strong antigen, become lymphoblastic,

c immature lymphocytes in the thymus, when

the injected antigen. Experiments have shown that

lymphocytes in the lymphoid tissue that are speci

fetus while the lymphocytes are being preprocessed in

and of B lymphocytes in the bone marrow. The reason

during preprocessing of T lymphocytes in the thymus

Most Tolerance Results from Clone Selection During Prepro-

activated T cells against his or her own antigens.

as being distinctive from bacteria or viruses, and the

s own body. The immune mech-

tissues, the process of acquired immunity would

s Own Tissues

System to One

Tolerance of the Acquired Immunity

, as we discuss in the

tissues, called

. It is probable that the suppressor T-cell

ulatory T cells

ed, along with the helper T cells, as

s own tissues. For this reason, the suppressor

purpose of preventing the cytotoxic cells from causing

the functions of both cytotoxic and helper T cells. It is

about the others, but they are capable of suppressing

Much less is known about the suppressor T cells than

Suppressor T Cells

s own body.

transplant cells, or other types of cells that are foreign

an important role in destroying cancer cells, heart

to the viral antigenicity. The cytotoxic cells also play

branes of the tissue cells and attract T cells in response

Some of the cytotoxic T cells are especially lethal to

cells persist for months in the tissues.

then move on to kill more cells. Indeed, some of these

Blood Cells, Immunity, and Blood Clotting

448

Unit VI

tissue cells that have been invaded by viruses because
many virus particles become entrapped in the mem-

to the person’

believed that these suppressor functions serve the

excessive immune reactions that might be damaging to
the body’
cells are classifi

reg-

system plays an important role in limiting the ability
of the immune system to attack a person’s own body

immune tolerance

next section.

’

—Role

of Preprocessing in the Thymus and
Bone Marrow

If a person should become immune to his or her own

destroy the individual’
anism normally “recognizes” a person’s own tissues

person’s immunity system forms few antibodies or

cessing.

It is believed that most tolerance develops

for this belief is that injecting a strong antigen into a

these two areas prevents development of clones of

fic for

specifi

stimulating antigen—an effect that is believed to cause
the cells themselves to be destroyed by the thymic
epithelial cells before they can migrate to and colonize

It is believed that during the preprocessing of lym-

fic to

damage the body’s own tissues are self-destroyed
because of their continual exposure to the body’s

eases.

Sometimes people lose their immune tolerance

tion of some of the body’
considerable quantities of “self-antigens” that cir-
culate in the body and presumably cause acquired

Several specific diseases that result from autoim-

munity include (1) rheumatic fever
becomes immunized against tissues in the joints and

specific type of streptococcal toxin that has an epitope
in its molecular structure similar to the structure of
some of the body’
glomerulonephritis
immunized against the basement membranes of

myasthenia gravis

develops against the acetylcholine receptor proteins of

lupus erythematosus
immunized against many different body tissues at the

often rapid death.

Immunization has been used for many years to
produce acquired immunity against specifi
person can be immunized by injecting dead organisms
that are no longer capable of causing disease but that

Cytotoxic

and

digestive

enzymes

Cytotoxic

T cells

(killer cells)

Antigen

receptors

Antigen

Attacked

cell

Specific
binding

Direct destruction of an invading cell by sensitized lymphocytes

Figure 34–8

(cytotoxic T cells).

directly into the circulation, the allergen can react with

When a speci

reactions caused in this manner are the following.

reaction occurs. Among the different types of allergic

several different tissue responses can occur, depend-

contraction of local smooth muscle cells. Therefore,

uid into the tissues; and

trophils to the reactive site; increased permeability of

local blood vessels; attraction of eosinophils and neu-

These substances cause such effects as dilation of the

, and

neutrophil chemo-

eosinophil chemotactic substance

slow-reacting substance of anaphy-

agents immediately or shortly thereafter, including

mast cells and basophils rupture; others release special

contort the cell membrane. At any rate, many of the

brane of the mast cell or basophil, perhaps resulting

basophil, this causes immediate change in the mem-

antibodies. Then, when an antigen (an allergen) that

and basophils. Indeed, a single mast cell or basophil

occurs.

reaction lakes place, and a subsequent allergic reaction

reagin antibody) enters the body, an allergen-reagin

ned as an antigen

bodies. When an

in the blood. These anti-

allergic tendency is genetically passed from parent to

by a nonordinary response of the immune system. The

tendency. Their aller-

Who Has Excess IgE Antibodies

Person,

attacks in the case of some airborne antigens.

is present, such as in the skin in the case of poison ivy,

can be serious tissue damage. The damage normally

their subsequent effects, one can well understand that

stances from the activated T cells as well as extensive

type of immune reaction. Remembering that this type

at the same time, these T cells elicit a cell-mediated

into the skin to respond to the poison ivy toxin. And,

ivy toxin, within a day or so, the activated T cells

T cells. Then, after subsequent exposure to the poison

cause the formation of activated helper and cytotoxic

to the tissues. However, on repeated exposure, it does

and not by antibodies. In the case of poison ivy, the

Delayed-reaction allergy is caused by activated T cells

Allergy Caused by Activated T Cells:

c allergic tendency.

several types of allergy and other hypersensitivities,

. There are

the development, under some conditions, of

immunity.

lymphocytes to confer immunity is called

from an animal. Such transfusion of antibodies or T

against the invading disease. Activated T cells last for

3 weeks, and during that time, the person is protected

infusing antibodies, activated T cells, or both obtained

person without injecting any antigen. This is done by

However, temporary immunity can be achieved in a

body develops either antibodies or activated T cells in

. That is, the person

Thus far, all the acquired immunity we have discussed

fever, measles, smallpox, and many other viral diseases.

dure is used to protect against poliomyelitis, yellow

c antigens required for immunization. This proce-

That is, these organisms either have been grown

nally, a person can be immunized by being

other similar toxic diseases.

used in immunizing against tetanus, botulism, and

causing immunity are still intact. This procedure is

bacterial diseases.

whooping cough, diphtheria, and many other types of

Resistance of the Body to Infection: II. Immunity and Allergy

Chapter 34

449

Immunity can be achieved against toxins that have

been treated with chemicals so that their toxic nature
has been destroyed even though their antigens for

And, fi

infected with live organisms that have been “attenu-
ated.”
in special culture media or have been passed through
a series of animals until they have mutated enough
that they will not cause disease but do still carry spe-
cifi

Passive Immunity

has been active immunity

’s own

response to invasion of the body by a foreign antigen.

from the blood of someone else or from some other
animal that has been actively immunized against the
antigen.

Antibodies last in the body of the recipient for 2 to

a few weeks if transfused from another person but
only for a few hours to a few days if transfused

passive

ALLERGY AND
HYPERSENSITIVITY

An important undesirable side effect of immunity is

allergy or

other types of immune hypersensitivity

some of which occur only in people who have a spe-
cifi

Delayed-Reaction Allergy

toxin of poison ivy in itself does not cause much harm

diffuse from the circulating blood in large numbers

of immunity can cause release of many toxic sub-

invasion of the tissues by macrophages along with

the eventual result of some delayed-reaction allergies

occurs in the tissue area where the instigating antigen

or in the lungs to cause lung edema or asthmatic

Allergies in the “Allergic”

Some people have an “allergic”
gies are called atopic allergies because they are caused

child and is characterized by the presence of large
quantities of IgE antibodies
bodies are called reagins or sensitizing antibodies to
distinguish them from the more common IgG anti-

allergen (defi

that reacts specifically with a specific type of IgE

A special characteristic of the IgE antibodies (the

reagins) is a strong propensity to attach to mast cells

can bind as many as half a million molecules of IgE

has multiple binding sites binds with several IgE anti-
bodies that are already attached to a mast cell or

from a physical effect of the antibody molecules to

his-

tamine, protease,
laxis (which is a mixture of toxic leukotrienes),

tactic substance, heparin

platelet activating factors.

the capillaries with loss of fl

ing on the type of tissue in which the allergen-reagin

Anaphylaxis.

fic allergen is injected

basophils of the blood and mast cells in the tissues

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removed. Administration of antihistaminics has less

sequently, the person has dif

causes spasm of the bronchiolar smooth muscle. Con-

, which

slow-reacting substance of anaphylaxis

occurs in the bronchioles of the lungs. Here, an impor-

person. In such a person, the allergen-reagin reaction

eliciting the typical sneezing syndrome.

reagin reaction can still cause irritation of the nose,

swelling reaction. But other products of the allergen-

again, use of antihistamine drugs can prevent this

nasal linings become swollen and secretory. Here

into associated deeper tissues of the nose; and the

increased capillary permeability. Both these effects

occurs in the nose.

In hay fever, the allergen-reagin reaction

Hay Fever.

the hives.

hives.

skin within another few minutes. The swellings are

reactions.

ing an asthma-like attack, sometimes causing death by

spasm of the smooth muscle of the bronchioles, elicit-

. These leukotrienes can cause

slow-reacting

epinephrine to oppose the effects of the histamine.

loss of plasma from the circulation. An occasional

anaphylaxis. Histamine

system and closely associated tissues. This is called

by attachment of IgE reagins. Therefore, a widespread

Blood Cells, Immunity, and Blood Clotting

450

Unit VI

located immediately outside the small blood vessels
if the basophils and mast cells have been sensitized

allergic reaction occurs throughout the vascular

is released into the circulation

and causes body-wide vasodilation as well as increased
permeability of the capillaries with resultant marked

person who experiences this reaction dies of circula-
tory shock within a few minutes unless treated with

Also released from the activated basophils and mast

cells is a mixture of leukotrienes called
substance of anaphylaxis

suffocation.

Urticaria.

Urticaria results from antigen entering spe-

cific skin areas and causing localized anaphylactoid

Histamine released locally causes (1) vasodi-

lation that induces an immediate red flare and (2)
increased local permeability of the capillaries that
leads to local circumscribed areas of swelling of the

commonly called

Administration of antihista-

mine drugs to a person before exposure will prevent

Histamine released in response to

the reaction causes local intranasal vascular dilation,
with resultant increased capillary pressure as well as

cause rapid fluid leakage into the nasal cavities and

Asthma.

Asthma often occurs in the “allergic” type of

tant product released from the mast cells is believed
to be the

ficulty breathing until the

reactive products of the allergic reaction have been

effect on the course of asthma because histamine does

not appear to be the major factor eliciting the asth-
matic reaction.

References

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defi

2004.

2003.

infl