Transcript Freeman 1e: How we got there

CHAPTER 22
Essentials of Immunology
Overview of the Immune
Response
Cells and Organs of the
Immune System
• All the cells involved in immunity originate
from common stem cells in the bone marrow
(Figure 22.1).
• The blood and lymph systems (Figure 22.2)
circulate cells and proteins that are important
for a functional immune system. Whole blood
is composed of plasma, a liquid containing
proteins and a variety of other solutes and
suspended cells.
• Outside the body, plasma quickly forms an
insoluble clot. Plasma remains liquid only
when an anticoagulant is added.
• After clotting, the remaining fluid, called
serum, contains no cells or clotting proteins.
Serum does, however, contain a high
concentration of other proteins, including
soluble antibody proteins, and is widely used
in immunological investigations. The use of
serum antibodies to detect antigens in vitro is
called serology.
• A variety of leukocytes participate in
immune responses.
The Innate Immune Response,
• The innate immune response is mediated by
phagocytes. Phagocytes recognize pathogenassociated molecular patterns (PAMPs) via
a family of membrane-bound patternrecognition molecules (PRMs) (Figure
22.5).
• Interaction of the PAMPs with PRMs
activates phagocytes to produce metabolic
products that kill the pathogen or limit its
effects (Figure 22.6). Many pathogens have
developed mechanisms to inhibit phagocytes.
Inflammation, Fever, and
Septic Shock
• Inflammation is characterized by pain,
swelling (edema), redness (erythema), and
heat. The inflammatory response is a normal
and generally desirable outcome of an
immune response. Uncontrolled systemic
inflammation, called septic shock, can lead to
serious illness and death.
• The first inflammatory cell to arrive at the
scene of an infection or tissue injury is the
neutrophil. These phagocytic cells are
attracted to the site of an active infection or
tissue injury by soluble chemoattractants
called chemokines.
• For example, IL-8 (interleukin-8), a small
protein in the chemokine family, is produced
by damaged host cells. Neutrophils migrate
toward the cells secreting IL-8 and are
activated by the interaction with IL-8.
The Adaptive Immune
Response
• In adaptive immunity, nonspecific
phagocytes present antigen to specific T cells,
triggering the production of effector T cells
and antibodies. Immune T cells and
antibodies react directly or indirectly to
neutralize or destroy the antigen.
• The adaptive immune response is
characterized by specificity for the antigen,
the ability to respond more vigorously when
reexposed to the same antigen (memory), and
the ability to discriminate self antigens from
nonself antigens (tolerance) (Figure 22.8).
• Antibody-mediated immunity is
particularly effective against pathogens such
as viruses and bacteria in the blood or lymph
and also against soluble pathogen products
such as toxins.
• Some T cells, the TC (T-cytotoxic) cells,
directly attack and destroy antigen-bearing
cells. Other antigen-activated T cells, the TH1
or T-helper 1 cells, act indirectly by secreting
proteins called cytokines that activate other
cells such as macrophages to destroy the
antigen-bearing cells.
• This cell-mediated immunity leads to
killing of pathogen-infected cells through
recognition of pathogen antigens found on
infected host cells.
Antigens, T Cells, and Cellular
Immunity
Immunogens and Antigens
• Immunogens are foreign macromolecules
that induce an immune response. Molecular
size, complexity, and physical form are
intrinsic properties of immunogens.
• Molecular size is an important component of
immunogenicity. For example, low-molecularweight compounds called haptens cannot
induce an immune response but can bind to
antibodies. Because haptens are bound by
antibodies, they are antigens even though they
are not immunogenic.
• When foreign immunogens are introduced
into a host in an appropriate dose and route,
they initiate an immune response.
• Antigens are molecules recognized by antibodies
or T-cell receptors (TCRs) (Figure 22.10).
• Antibodies recognize conformational determinants; TCRs
recognize linear peptide determinants (Figure 22.9).
• The antibody or TCR does not interact with
the antigenic macromolecule as a whole but
only against a distinct portion of the molecule
called an antigenic determinant or epitope.
Presentation of Antigen to T Lymphocytes
• T cells recognize antigens presented by
antigen-presenting cells (APCs) or by
pathogen-infected cells.
• At the molecular level, TCRs bind peptide antigens
presented by major histocompatibility complex
(MHC) proteins. Class I MHC proteins are found
on the surfaces of all nucleated cells.
• Class II MHC proteins are found only on the
surface of B lymphocytes, macrophages, and
dendritic cells, all of which are APCs (Figure 22.11).
• These molecular interactions stimulate T
cells to kill antigen-bearing cells or to produce
cell-stimulating proteins known as cytokines.
• Figure 22.12 illustrates antigen presentation
by MHC I and MHC II proteins.
T-Cytotoxic Cells and Natural
Killer Cells
• T-cytotoxic (TC) cells recognize antigens on
virus-infected host cells and tumor cells
through antigen-specific TCRs. Antigenspecific recognition triggers killing via
perforin and granzymes (Figure 22.13).
• Natural killer (NK) cells use the same
effectors to kill virus-infected cells and
tumors. However, NK cells do not require
stimulation, nor do they exhibit memory. NK
cells respond in the absence of MHC proteins.
T-Helper Cells: Activating the
Immune Response
• TH1 and TH2 cells play pivotal roles in cellmediated and antibody-mediated immune
responses.
• Following the initial antigen exposure, each
antigen-stimulated B cell multiplies and
differentiates to form both antibody-secreting
plasma cells and memory cells (Figure 22.14). TH1
inflammatory and TH2 helper cells each stimulate
effector cells through the action of cytokines.
PART III Antibodies and
Immunity, p. 743
22.9 Antibodies
(Immunoglobulins) , p. 744
• Immunoglobulin (Ig) (antibody) proteins
consist of four chains, two heavy and two
light (Figure 22.15). Each IgG light chain
consists of two protein domains of equal size.
• The amino-terminal region is a variable
domain, meaning that the amino acid
sequence in this structural region differs in
each different antibody. The antigen-binding
site is formed by the interaction of variable
regions of heavy and light chains (Figure
22.16).
• Each class of Ig has different structural and
functional characteristics (Figure 2.17; Table 22.2).
• The structure of IgM is shown in Figure 22.18.
Figure 22.19 shows the structure of IgA.
Antibody Production
• Antibody production is initiated by antigen
contact with an antigen-specific B cell that
processes the antigen and presents it to an
antigen-specific TH2 cell. The activated TH2
cell then signals the antigen-specific B cell to
produce antibody.
• Figure 22.20 shows a typical rearrangement and
expression pattern for the human kappa light chain.
• Activated B cells live for years as memory cells and
can rapidly produce large quantities (high titers) of
antibodies upon reexposure to antigen (Figure 22.21).
• Plasma cells are relatively short-lived (less than 1
week), but produce and secrete large amounts of IgM
antibody in this primary antibody response.
• The memory B cells generated by the initial
exposure to antigen may live for years. If reexposure
to the immunizing antigen occurs at a later time,
memory cells need no T-cell activation; they quickly
transform to plasma cells and begin producing IgG.
• Upon reexposure, the antibody titer rises rapidly to a
level 10–100 times greater than the titer achieved
following the first exposure. This rise in antibody titer
is referred to as the secondary antibody response.
Complement, Antibodies, and
Pathogen Destruction
• The complement system catalyzes bacterial cell
destruction and opsonization (Figure 22.22).
• Complement is triggered by antibody
interactions or by interactions with
nonspecific activators. Complement is a
critical component of both innate and adaptive
host defense.
Immunity and Prevention of
Infectious Disease
Natural Immunity
• Innate and adaptive immune responses are
necessary for survival. Lack of innate
immunity results in death due to recurrent,
uncontrollable infections. Lack of adaptive
immunity also results in uncontrollable
infectious disease.
Artificial Immunity
• Immunity to infectious disease can be either
passive or active, natural or artificial (Table
22.3).
• Many exotoxins can be modified chemically
so that they retain their antigenicity but are no
longer toxic. Such a modified exotoxin is
called a toxoid.
• Immunization, a form of artificial active
immunity, is widely employed to prevent
infectious diseases (Table 22.4; Figure
22.24).
• Most agents used for immunization are
either attenuated or inactivated pathogens or
inactivated forms of natural microbial
products.
New Immunization Strategies
• Alternative immunization strategies using
bioengineered molecules eliminate exposure
to microorganisms and, in some cases, even
to protein antigen. Application of these
strategies may provide safer and more
targeted vaccines.
Immune Response Diseases
Allergy, Hypersensitivity, and
Autoimmunity
• Hypersensitivity results when foreign
antigens induce cellular or antibody immune
responses, leading to host tissue damage.
• Table 22.5 lists the four types of
hypersensitivity. Autoimmunity occurs when
the immune response is directed against self
antigens, resulting in host tissue damage.
• Immediate (Type I) hypersensitivity
reactions, commonly called allergies, occur
within minutes after exposure to antigen
(Figure 22.25; Table 22.6).
• Type IV hypersensitivity, or delayed-type
hypersensitivity (DTH), is cell-mediated
hypersensitivity characterized by tissue
damage due to inflammatory responses
produced by TH1 inflammatory cells.
• Typical antigens include certain microorganisms, a
few self antigens (Table 22.7), and several chemicals
that bind covalently to the skin, creating new
antigens. Autoantibodies are antibodies that react to
self antigens.
Superantigens
• Superantigens bind and activate large
numbers of T cells in a novel fashion (Figure
22.27). Superantigen-activated T cells are
capable of producing systemic diseases
characterized by massive inflammatory
reactions.