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CHAPTER
16
Adaptive Immunity
Chapter Outline
Overview of Adaptive Immunity (pp. 464–465)
Elements of Adaptive Immunity (pp. 465–478)
The Tissues and Organs of the Lymphatic System
Antigens
B Lymphocytes (B Cells) and Antibodies
T Lymphocytes (T Cells)
Clonal Deletion
Immune Response Cytokines
Preparation for an Adaptive Immune Response (pp. 478–480)
The Roles of the Major Histocompatibility Complex and Antigen-Presenting Cells
Antigen Processing
Cell-Mediated Immune Responses (pp. 480–483)
Activation of Cytotoxic T Cell Clones and Their Functions
The Perforin-Granzyme Cytotoxic Pathway
The CD95 Cytotoxic Pathway
Memory T Cells
T Cell Regulation
Antibody Immune Responses (pp. 483–487)
Inducement of T-Independent Antibody Immunity
Inducement of T-Dependent Antibody Immunity with Clonal Selection
Memory B Cells and the Establishment of Immunological Memory
Types of Acquired Immunity (pp. 487–489)
Naturally Acquired Active Immunity
Naturally Acquired Passive Immunity
Artificially Acquired Active Immunity
Artificially Acquired Passive Immunotherapy
Chapter Summary
Overview of Adaptive Immunity (pp. 464–465)
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Adaptive immunity is the body’s ability to recognize and then mount a defense against specific invaders and their
products.
Adaptive immunity has five distinct attributes:
1. Specificity. Adaptive immune responses are precisely tailored reactions against specific attackers.
2. Inducibility. Cells of adaptive immunity activate only in response to specific pathogens.
3. Clonality. Once induced, cells of adaptive immunity proliferate to form many generations of nearly identical cells called clones.
4. Unresponsiveness to self. As a rule, adaptive immunity does not act against normal body cells.
5. Memory. An adaptive immune response generates faster and more effective responses in subsequent encounters with a particular pathogen or toxin.
These aspects of adaptive immunity involve the activities of lymphocytes, which are a type of leukocyte (white
blood cell) that acts against specific pathogens. Lymphocytes of humans form in the red bone marrow. There are
two main types of lymphocytes. B lymphocytes (B cells) arise and mature in the red bone marrow of adults. T lymphocytes (T cells) begin in the bone marrow but mature in the thymus.
Adaptive immunity consists of two basic types of responses. Antibody (humoral) immune responses involve the
descendants of activated B cells and the soluble proteins they secrete called antibodies. Antibody immune responses
are often directed against extracellular pathogens and toxins. T cells mount cell-mediated immune responses,
which do not involve antibodies. Cell-mediated immune responses often act against intracellular pathogens. The
long-term ability of descendants of B and T cells to mount adaptive immunological responses against specific pathogens is called immunological memory.
Elements of Adaptive Immunity (pp. 465–478)
The following sections present elements of adaptive immunity by describing the “stage” and introducing the “characters” involved in adaptive immunity.
The Tissues and Organs of the Lymphatic System
The lymphatic system is composed of lymphatic vessels, which conduct the flow of lymph—a colorless, watery liquid similar in composition to blood plasma—from local tissues and returns it to the circulatory system. It also includes lymphoid tissues and organs that are directly involved in adaptive immunity. Lymphocytes arise in the
primary lymphoid organs of the bone marrow and thymus. Lymphocytes then migrate to secondary lymphoid organs
and tissues, including lymph nodes, the spleen, the tonsils, and mucosa-associated lymphatic tissue (MALT).
Antigens
Antigens are portions of cells, viruses, and molecules the body recognizes as foreign. The three-dimensional shape
of a region of an antigen that is recognized by the immune system is the epitope (or antigenic determinant).
EPITOPE = PART OF THE ANTIGEN THAT IS RECOGNIZED BY THE IMMUNE SYSTEM, SPECIFICALLY
BY ANTIBODIES, B CELLS OR T CELLS. Effective antigen molecules are large, complex, and foreign to their
host. The most effective antigens, therefore, are large foreign macromolecules such as proteins and glycoproteins but
complex carbohydrates and lipids, as well as some nucleic acids, can also be antigenic.
Although immunologists characterize antigens in various ways, one important way is to group them according to
their relationship to the body:
 Exogenous antigens include toxins and other secretions and components of microbial cell walls, membranes, flagella, and pili.
 Protozoa, fungi, bacteria, and viruses that reproduce inside a body’s cells produce endogenous antigens. The
immune system can “see” and respond to these antigens only if they are incorporated into the cell’s cytoplasmic
membrane.
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 Autoantigens (or self-antigens) are antigenic molecules derived from normal cellular processes. Immune cells
that treat autoantigens as foreign are normally eliminated during the development of the immune system. This phenomenon, called self-tolerance, prevents the body from mounting an immune response against itself.
B Lymphocytes (B Cells) and Antibodies
B lymphocytes are found in the spleen, MALT, and primary follicles of lymph nodes. The major function of B cells
is to secrete soluble antibodies. The specificity of B cell function comes from the membrane proteins called B cell
receptors.
The surface of each B cell is covered with about 500,000 identical copies of the B cell receptor (BCR), a type of
immunoglobulin (Ig). Simple immunoglobulin contains four polypeptide chains—two heavy chains and two light
chains—linked with disulfide bonds in such a way that a basic antibody molecule looks like the letter Y. A BCR has
two arms and a transmembrane portion. The transmembrane portion anchors the BCR in the cytoplasmic membrane.
The arms of each heavy and light chain vary in amino acid sequence, and thus each is called a variable region. The
two variable regions form antigen-binding sites. Exact binding between an antigen-binding site and an epitope accounts for the specificity of an antibody immune response. Because an antigen typically has numerous epitopes,
many different BCRs will recognize any particular antigen’s epitopes, but each BCR recognizes only one epitope.
When an antigenic epitope stimulates a specific B cell, B lymphocytes called plasma cells are produced. Plasma
cells secrete immunoglobulins, called antibodies, into the blood or lymph.
Antibodies are similar to BCRs in shape, but are secreted and lack most of the transmembrane portion of BCRs.
Antibodies carry the same specificity for an epitope as the BCR of the activated B cell. The arms, or Fab region, of
the antibody contain the antigen-binding sites. The antibody stem is called the Fc region. There are five basic types
of stems, and these form the five classes of antibodies: IgM, IgG, IgA, IgE, and IgD.
Once antibodies are bound to antigens, they function in several ways. These include:
 Activation of complement and inflammation (discussed in Chapter 15)
 Neutralization of toxins, which antibodies achieve by binding to critical portions, or neutralization of bacteria or
viruses, which antibodies achieve by blocking attachment molecules on their surfaces
 Opsonization, whereby antibodies act as opsonins to stimulate phagocytosis
 Killing by oxidation, whereby some antibodies with catalytic properties kill bacteria directly
 Agglutination, which is the clumping of antigen-bound antibody molecules, and which may hinder the activity of
pathogens and increase the chance that they will be phagocytized
 Antibody-dependent cellular cytotoxicity (ADCC), which is similar to opsonization except that antibodies interact with NK cells and the target cell dies by apoptosis.
The class of antibody involved in any given antibody immune response depends on the type of invading foreign
antigen, the portal of entry, and the antibody function required:
 Immunoglobulin M (IgM) is the first antibody secreted during the initial stages of an immune response. It is secreted as a pentamer and is most efficient at complement activation.
 Immunoglobulin G (IgG) is the most common and longest lasting class of antibody in the blood. IgG is the only
antibody that can cross the placenta.
 Immunoglobulin A (IgA) is the antibody class most closely associated with various body secretions. Two IgA
monomers, a J chain, and a secretory component combine to form secretory IgA.
 Immunoglobulin E (IgE) triggers mast cells and basophils to release inflammatory chemicals, such as histamine,
associated with allergies.
 Immunoglobulin D (IgD) is a membrane-bound antibody molecule found in some animals as a B cell receptor.
T Lymphocytes (T Cells)
An adult’s red bone marrow produces T lymphocytes. Following maturation in the thymus, T cells circulate in the
lymph and blood, and migrate to the lymph nodes, spleen, and Peyer’s patches. Each T cell has about 500,000 copies
of a T cell receptor (TCR) on its cytoplasmic membrane. A TCR does not bind epitopes directly, but instead binds
only to an epitope associated with a particular protein called MHC protein.
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Immunologists recognize different types of T cells:
 Cytotoxic T cells are distinguished by the presence of the CD8 cell-surface glycoprotein. They directly kill
infected cells, as well as abnormal body cells such as cancer cells. A SINGLE CYTOTOXIC T LYMPHOCYTE
CAN KILL MANY TARGET CELLS.
 Helper T cells have the CD4 glycoprotein. They help to regulate the activity of B cells and cytotoxic T cells
during an immune response. There are two main subpopulations: Th1 cells assist cytotoxic T cells and innate
macrophages, and Th2 cells function in conjunction with B cells.
 Regulatory T cells express CD4 and CD25 glycoproteins. They repress adaptive immune responses and prevent
autoimmune diseases.
Clonal Deletion
Cells with receptors that respond to autoantigens are selectively eliminated via apoptosis in a process known as
clonal deletion (because potential offspring—clones—are deleted). Clonal deletion of T cells occurs in the thymus,
where thymus cells process and present all the body’s autoantigens to young T cells. Clonal deletion of B cells occurs in the bone marrow in a manner similar to that in T cells. Surviving lymphocytes and their descendants respond
only to foreign antigens. When self-tolerance is impaired, the result is an autoimmune disease.
Immune Response Cytokines
Cytokines are soluble regulatory proteins that act as intercellular signals when released by certain body cells such as
kidney cells, skin cells, and immune cells. Cytokines of the immune system include:
 Interleukins (ILs), which signal among leukocytes
 Interferons (IFNs), which are antiviral proteins that also act as cytokines
 Growth factors, which stimulate stem cells to divide
 Tumor necrosis factor (TNF), which is secreted by macrophages and T cells to kill tumor cells and to regulate
immune responses
 Chemokines, which signal leukocytes to move to a site of inflammation or infection, or to move within tissues
Preparation for an Adaptive Immune Response (pp. 478–480)
The body prepares for adaptive immune responses by making major histocompatibility complex proteins and processing antigens so that they can be recognized by T lymphocytes.
The Roles of the Major Histocompatibility Complex and Antigen-Presenting Cells
The major histocompatibility complex is a cluster of genes located on each copy of chromosome 6 (in humans),
which codes for major histocompatibility antigens. These antigens, which are present in the membranes of most cells
of vertebrate animals, hold and position epitopes for presentation to T cells. THE MAIN FUNCTION OF MHC
MOLECULES IS TO BIND TO PEPTIDE FRAGMENTS DERIVED FROM PATHOGENS AND DISPLAY
THEM ON THE CELL SURFACE FOR RECOGNITION BY THE APPROPRIATE T CELLS. Class I MHC molecules are found on the cytoplasmic membranes of all cells except red blood cells, CAN ONLY BE RECOGNIZED
BY CD8 CORECEPTORS. Class II MHC proteins are found only on special cells called antigen-presenting cells
(APCs). These include B cells, macrophages, and dendritic cells. CLASS II MHC CAN BE RECOGNIZED BY
CD4 CORECEPTORS. Other phagocytes, such as microglia and stellate macrophages, present antigen only under
certain conditions and are called nonprofessional antigen-presenting cells.
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Antigen Processing
Antigens must be processed before MHC proteins can display epitopes. Peptides containing epitopes from endogenous antigens bind MHC class I molecules during biosynthesis in the membrane of the endoplasmic reticulum. Antigen-presenting cells internalize exogenous antigens and catabolize the molecules to produce peptide epitopes, which
bind to MHC class II molecules. The MHC I/II-epitope complex is then displayed on the cell’s surface.
Cell-Mediated Immune Responses (pp. 480–483)
The body uses cell-mediated immune responses to fight intracellular pathogens such as viruses that have invaded
body cells, as well as abnormal body cells such as cancer cells.
Activation of Cytotoxic T Cell Clones and Their Functions
An adaptive immune response is initiated in lymphoid organs where antigen-presenting cells interact with lymphocytes. It occurs through the following series of steps:
1. Antigen presentation
2. Helper T cell differentiation
3. Clonal expansion
4. Self-stimulation
The Perforin-Granzyme Cytotoxic Pathway
In the perforin-granzyme pathway, cytotoxic T cells destroy their targeted cells by secreting perforins and
granzymes, toxic protein molecules. Perforins perforate cytoplasmic membranes, and granzymes enter the target cell
and activate apoptosis, thereby forcing the cell to commit suicide.
The CD95 Cytotoxic Pathway
In the CD95 cytotoxic pathway, cytotoxic T cells contact their target cells, and their CD95L protein binds with
CD95 on the target cell, thereby activating enzymes that trigger apoptosis.
Memory T Cells
Some activated T cells become memory T cells and can persist for months or even years in lymphoid tissues. Contact with an epitope-MHC I complex matching its TCR prompts the memory T cell to immediately produce cytotoxic T cells. A memory response is more rapid and more effective than a primary response.
T Cell Regulation
The body carefully regulates cell-mediated immunity so that T cells do not respond to autoantigens. To prevent autoimmunity, T cells require additional signals from an APC. If they do not receive these signals, they will not respond.
Antibody Immune Responses (pp. 483–487)
Inducement of T-Independent Antibody Immunity
Because some large antigens have repeating epitopes that can be processed by B cells without the help of T cells,
they are called T-independent antigens. The repeating subunits of T-independent antigens allow extensive crosslinking between numerous BCRs on a B cell, stimulating the B cell to proliferate. T-independent antibody immunity
is relatively weak, disappears quickly, and induces little immunological memory.
Inducement of T-Dependent Antibody Immunity with Clonal Selection
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T-dependent antigens lack the numerous, repetitive epitopes and large size of T-independent antigens. Immunity
against them requires the assistance of type 2 helper T (Th2) cells. A T-dependent antibody immune response involves the following series of interactions among antigen-presenting cells, helper T cells, and B cells, which are mediated by cytokines:
1. Antigen presentation for Th activation and cloning
2. Differentiation of helper T cells into Th2 cells
3. Activation of B cell by the Th2 cell such that it proliferates rapidly and differentiates into either a memory B cell
or plasma cell
Plasma cells initially secrete IgM but through class switching secrete IgG, and may switch again to secrete IgA or
IgE. As the antibody immune response progresses, plasma cells that secrete antibody with a higher affinity for the
epitope survive at a higher rate such that the antibody specificity becomes progressively better over the course of the
immune response.
Memory B Cells and the Establishment of Immunological Memory
A small percentage of the cells produced by B cell proliferation do not secrete antibodies but survive as memory B
cells, long-lived cells with BCRs complementary to the specific antigen that triggered their production. In a primary
immune response, it can take days for relatively small amounts of antibodies to be produced. When an antigen is
encountered a second time, the activation of memory cells in the secondary immune response ensures that the immune response is rapid and strong. Enhanced immune responses to subsequent exposures are called memory responses.
Types of Acquired Immunity (pp. 487–489)
Immunologists categorize specific immunity as either naturally or artificially acquired, and as either active or passive.
Naturally Acquired Active Immunity
Naturally acquired active immunity occurs when the body responds to exposure to antigens by mounting specific
immune responses.
Naturally Acquired Passive Immunity
Naturally acquired passive immunity occurs when a fetus, newborn, or child receives antibodies across the placenta
(IgG) or within breast milk (IgA).
Artificially Acquired Active Immunity
Artificially acquired active immunity occurs when the body receives antigens as vaccinations, and mounts a specific
immune response. MOST EFFICIENT AND COST EFFECTIVE WAY TO CONTROL INFECTIOUS DISEASEIS
TO RECEIVE ARTIFICIALLY ACTIVE IMMUNIZATION VIA VACCINATIONS.
Artificially Acquired Passive Immunotherapy
Artificially acquired passive immunotherapy occurs when the body receives, via injection, preformed antibodies in
antitoxins or antisera, which can destroy fast-acting and potentially fatal pathogens such as rabies virus.
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